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Report On An overview of natural micronized progesteron ,drospirenon/ethynil estradiol combination &ivf market in luck now Done at lupin

limited (luck now)

And submitted as a part of curriculum of Pgdm course of School of management sciences (Varanasi)

Submitted by Shweta singh Sms,varanasi



This survey has been conduced to take the OVERVIEW OF NATURAL MICRONISED PROGESTERON, DROSPIRENON/ETHYNIL ESTRADIOL AND IVF MARKET OF LUCKNOW. This survey is carried to translate the theoretical knowledge of subject into practical field work. This survey report basically delivers deeper knowledge regarding movement of NATURAL MICRONISED PROGESTERON & COMBINED ORAL CONTRACEPTIVES PILLS industry as a whole so as to find the trends of these pills in Lucknow. This survey also touches various aspects of IVF market. Through report, I have genuinely tried to map doctors/general retailer’s opinion, demand, requirement and satisfaction level regarding quality, content and presentation of above said in the market of Lucknow. The complete process was a good learning experience for me.



I am grateful to Mr. S.K. Pandey,Deputy General Manager, Lupin Limited who gave me a golden opportunity to work with one of the best pharmaceutical company of country. My sincere thanks to Mr. Ashutosh Jain, Regional Sales Manager, Lupin Limited, Lucknow without whose guidance and whole-hearted encouragement, it would not be possible for me to complete this report. I am also greatful to Mr.Mohd. Furquan, Area Manager, Lupin Parma, Lucknow who guided me at every step during the completion of this project . I am also grateful to Mr. Neeraj Kalra and Mr.Yogesh Mishra, Medical Representative; for their kind-hearted cooperation. I also want to give thanks to Mr. Neeraj Srivastav ;Training & Placement Coordinator of SMS,Varanasi who recommended me in Lupin Limited.



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Company profile
Headquartered in Mumbai, India, Lupin Limited is an innovation led transnational pharmaceutical company producing a wide range of quality, affordable generic and branded formulations and APIs for the developed and developing markets of the world. The Company today has significant market share in key markets in the Cardiovasculars (prils and statins), Diabetology, Asthma, Pediatrics, CNS, GI, Anti-Infectives and NSAIDs therapy segments, not to mention global leadership positions in the Anti-TB and Cephalosporin. The Company’s R&D endeavors have resulted in significant progress in its NCE program. The Company’s foray into Advanced Drug Delivery Systems has resulted in the development of platform technologies that are being used to develop valueadded generic pharmaceuticals. Our Drugs and products reach over 70 countries in the world. Today, Lupin has the unique distinction of being the fastest growing top 10 Generics players in the two largest pharmaceutical markets of the world – The U.S (ranked 9th by prescriptions & growing at 92 %) and Japan (ranked 7th and growing at 23%). The company is also the fastest growing, top 5 pharmaceutical players in India (ORG IMS - March 2009) and the fastest growing Generic player in South Africa (ranked 6th and growing at over 30 % YoY - IMS). For the financial year ended March 2009, Lupin’s consolidated revenues and profit after Tax were Rs 39,145 million and Rs. 5015 million respectively. Lupin Limited is the India’s 5th largest drugs firm and its 2007 revenue was Rs.2215.52 crore. Lupin is one of the fastest growing pharmaceutical companies in India with an annual turnover of approximately US $ 1bilion with exports contributing to 50% of the total sales.At present Lupin stands at No.5 in Indian Pharmaceutical market. Lupin is having a consistent track record in supplying quality goods all


over the world. Manufacturing facilities are spread over five plants in India and one in Thailand employing over 3300 people of which around 400 are of Managerial cadre, 600 technical and 1000 strong field force. Lupin’s Research & Development centre at Pune, approved by Government of India have over hundred qualified Scientists and Research Professionals and spends 5.6% of its annual turnover on its R&D. From a modest beginning in 1968, Lupin has grown by leaps and corner and today it has the distinction of being the biggest producer of Ethambutol HCl in the world. The strength of Lupin in these fields can be gauged by the fact that almost 70% of the world’s Ethambutol production is accounted for by Lupin and even many multinationals in developed markets buy the raw materials from Lupin. Lupin is also one of the leading producers of Rifampicin, which is manufactured from fermentation stage. The plant for bulk production of Rifampicin has been approved by Foods & Drugs Administration of USA. Lupin is mainly considered with the therapy of the diseases. The therapeutic areas include, among others, anti-TB, cephalosporins,

cardiovasculars and non-steroidal anti-inflammatory drugs (NSAIDs). The company caters to generics markets in the US and Europe through strategic marketing alliances.



Progesterone is one of the two primary female hormones. As the name implies, progesterone prepares ("pro") the womb for pregnancy (gestation). Progesterone works in tandem with estrogen; indeed, if estrogen is taken as a medication without being balanced by progesterone (so called unopposed estrogen), there is an increased risk of uterine cancer. However, progesterone is not well absorbed orally. For this reason, pharmaceutical manufacturers developed "progestins," substances similar to progesterone which are more easily absorbed. Most of the time, a woman prescribed "progesterone" is really being given a progestin. Two of the most commonly used progestins are medroxyprogesterone and norethindrone. However, it has been suggested that actual progesterone may offer benefits over progestins, such as fewer side effects. Progesterone can be absorbed through the skin to some extent, and some alternative practitioners have, for years, promoted the use of progesterone creams. Such progesterone creams are typically, but misleadingly, said to contain "natural" progesterone. This is an oddly chosen term, as the progesterone in these creams is actually produced in a laboratory, just like other synthetic hormones. To avoid confusion in this article, we will call progesterone "true" progesterone, or just "progesterone." Besides creams, a special form of true progesterone that can be absorbed orally, micronized progesterone, has recently become available as a prescription drug. Inconsistent evidence suggests that progesterone cream might help reduce menopausal symptoms. However, it does not appear to be strong enough to balance the effects of estrogen, thus reducing the risk of uterine cancer. (Oral micronized progesterone is strong enough for this purpose.) Contrary to numerous books and magazine articles, there is no more than weak, inconsistent evidence that progesterone cream offers any benefits for osteoporosis.

Requirements/Sources Progesterone is synthesized in the body and is not found in appreciable quantities in food. For use as a drug or dietary supplement, progesterone is synthesized from chemicals found in soy or Mexican yam. Note: Another aspect of the widespread misinformation involving progesterone cream is the concept that Mexican yam itself contains progesterone, or substances that the body can convert into progesterone. This is incorrect. Industrial chemists can convert a constituent of Mexican yam (diosgenin) into progesterone, but only by using chemical pathways not found in the body.

Therapeutic Dosages The usual dose of progesterone in cream form is 20 mg daily. Although this dose might decrease menopausal hot flashes (see below), most studies found that even doses as high as 64 mg daily do not provide enough progesterone to protect the uterus from the effects of estrogen. However, one study found that use of micronized progesterone cream at 80 mg daily produced similar progesterone levels in the body as an oral dose of 200 mg daily; oral micronized progesterone taken at a dose of 200 to 400 mg daily is approximately as effective as the standard dosage of the more commonly used progestins. Therapeutic Uses Progesterone cream was widely promoted in the 1990s a treatment for osteoporosis, on the basis of meaningless “studies” whose designs were too poor to establish anything at all. When properly designed studies were performed, the results were at best inconsistent. Studies conflict on whether progesterone cream can help hot flashes. One doubleblind, placebo-controlled study failed to find any improvements in mood or general well-being in menopausal women using progesterone cream.


Like progestins, oral progesterone protects the uterus from the stimulating effects of unopposed estrogen. However, standard doses of progesterone cream probably provide too little progesterone to serve for this purpose (see next section). What Is the Scientific Evidence for Progesterone? Osteoporosis Despite widespread reporting that true progesterone is effective for treating or preventing osteoporosis, the evidence for such an effect is at best inconsistent. This notion began with test tube and other preliminary studies suggesting that progesterone or progestins can stimulate the activity of cells that build bone. Subsequently, a poorly designed and uncontrolled study (really, a series of case histories from one physician's practice) purportedly demonstrated that progesterone cream can slow or even reverse osteoporosis. However, a 1-year, double-blind trial of 102 women given either progesterone cream (providing 20 mg progesterone daily) or placebo cream, along with calcium and multivitamins, found no evidence of any improvements in bone density attributable to progesterone. A smaller, short-term trial found that progesterone cream has no effect on bone metabolism. In contrast to these negative results, benefits were seen in a small 2-year, doubleblind, placebo-controlled study in which 22 women were given progesterone cream. (Interestingly, in this study, use of progesterone cream plus soy isoflavones produced inferior benefits to those of progesterone cream alone.) It is, therefore, at least possible that progesterone cream is helpful for osteoporosis if taken for a long enough period; however, more research is needed. Menopausal Symptoms In the 1-year, double-blind trial of 102 women described above, use of progesterone cream was found to significantly reduce hot flashes and related symptoms. However, a slightly smaller 12-week, double-blind trial failed to find progesterone cream helpful for reducing menopausal symptoms. The authors of this second study point out that the first study was statistically flawed. Opposing Estrogen Unless you have had a hysterectomy, if you take estrogen you need to take progesterone too, or run the risk of uterine cancer. Two 12-week, double-blind

studies enrolling a total of about 100 women found that progesterone cream (at doses up to 64 mg) did not have the required protective effect on the cells of the uterus. One study, however, did find benefit at dosages of either 15 or 40 mg daily. The explanation for these disparate results may lie in the results of two other studies, which suggest that progesterone cream is erratically absorbed. Safety Issues Even though progesterone is sold as a dietary supplement, it is a hormone, not a food. We recommend that it not be used except under physician supervision. Like progestins, true progesterone causes side effects. In one study, oral micronized progesterone at a dose of 400 mg per day was associated with dizziness, abdominal cramping, headache, breast pain, muscle pain, irritability, nausea, fatigue, diarrhea, and viral infections.

Micronized progesterone: A new option for women's health careAlthough progestational agents have been widely used for gynecologic conditions, treatment options have usually been limited to synthetic agents with adverse effects and sparse patient acceptance. Recent Food and Drug Administration approval of oral micronized progesterone (MP) has introduced therapy with a safe, effective, well-tolerated drug. This article reviews therapeutic Indications for MP as illustrated in five case studies. Issues of patient compliance, individualized treatment plans, and patient partnership to obtain the most beneficial outcomes are discussed.

Hormone interventions have become increasingly prominent features of women's health care. Improved estrogenic compounds have appeared on the market, but progestogen's availability has been limited.

Progesterone, discovered in 1934, has long been recognized as a fundamental female hormone with potential treatment uses. However, therapeutic options have been limited to a few synthetic agents. These progestins have been effective in endometrial protection and menstrual regulation, but often cause unwanted adverse effects that reduce patient satisfaction and compliance.1,2


In May 1998, the Food and Drug Administration (FDA) approved micronized progesterone (MP, Prometrium), provided in an oral gel cap, for use in secondary amenorrhea. The progesterone used in this product is derived from the yam plant and is chemically identical to the human hormone, thus offering distinct advantages over synthetic progestins. Approval for hormone replacement therapy (HRT) was granted in December 1998. Meanwhile, clinicians are likely to begin to prescribe human-- identical progesterone for all conditions that call for progestational support. Synthetic versus Natural Progesterone The ovary creates progesterone in response to ovulation and the formation of the corpus luteum. Besides supporting pregnancy, progesterone plays a key role in other phases of female physiology, including regulating the menstrual cycle and protecting the endometrium against hyperplasia.3-5 A hormone defined as natural is indigenous to the species, produced by the endocrine system, and free from chemical variation. In common parlance, the term natural refers to components from non synthetic sources, primarily botanical ones, that are identical in structure to their human counterparts. The term humanidentical hormone (HIH) was coined to overcome the intrinsic difficulties of identifying what is natural. An HIH is not human in origin but is identical in structure and function to human hormones without being chemically altered.6 Pure progesterone cannot be taken orally because it is rendered ineffective by normal gastric secretions and the first-pass liver effect. Various chemical alterations to enhance the bioavailability of the oral form have been attempted; however, the resulting compounds exhibit slightly different biologic actions from those of native progesterone. Although these products are effective, they cause numerous and often bothersome adverse effects, including dysphoria, bloating, weight gain, depression, and headaches.1,4,5,7,8 Medroxyprogesterone acetate (MPA; Cycrin, Provera) and norethindrone acetate (found in many oral contraceptives and in Aygestin) have been used extensively to treat dysfunctional uterine bleeding, oligomenorrhea, secondary amenorrhea, polycystic ovarian syndrome, and endometrial hyperplasia. The two drugs are often components of HRT as well. Although these agents' clinical value has been well documented, they tend to be poorly tolerated. Many patients discontinue use without consulting their health care providers. MPA has been identified as a vasoconstrictor and has been found to

cause or exacerbate angina in susceptible individuals. MPA can offset the increased high-density lipoprotein cholesterol levels achieved with estrogen replacement. These findings may indicate that MPA negates the cardiovascular protection offered by estrogen therapy. Investigators have suggested that MPA demonstrates an adverse alteration to clotting function, raises blood pressure, and may be teratogenic or, in large doses, carcinogenic.5,9-12 Although research and clinical practice support the use of synthetic progestins in HRT, FDA approval of MPA for this indication did not occur until August 1998. MPA may, under this indication, be used only when taken in a cyclic regimen to reduce endometrial hyperplasia with a specific dose of conjugated equine estrogen.1-3, 8,9,11,13 Micronization of progesterone for oral use increases the surface area contact between the steroid molecule and the mucosa.14 Suspending progesterone in a long chain fatty acid leads to adequate absorption through the gastric mucosa, as measured by serum levels. Proponents assert that because of the human-analogous structure of MP, the drug is generally well-tolerated, does not produce the same unacceptable adverse effect profile as synthetic compounds, and provides similar therapeutic benefits.4, 14-6 The Postmenopausal Estrogen/Progestin Interventions (PEPI) Trial documented that MP provides adequate protection from endometrial hyperplasia without reversing estrogen's positive impact on the lipid profile." MP does not appear to affect carbohydrate metabolism, liver function, or clotting mechanisms. Some authors suggest that progesterone assists with thyroid function, prevents fibrocystic breast changes and fluid retention, and may serve as an antidepressant.4,5,8,12,17 Progesterone may play a key role in bone formation, whereas the synthetic progestins may be implicated in bone loss. Progesterone receptors are suspected to exist in osteoblasts. Researchers also suspect that adequate progesterone levels stimulate the growth of new bone, whereas estrogen slows bone resorption.4,17-20 MP has been used in Europe and Canada for more than 10 years. The FDA approved progesterone gel in a bioadhesive base (Crinone) for use as progesterone supplementation for assisted reproductive technology in 1997 and for secondary amenorrhea in 1998. No indications for using the gel with other gynecologic diagnoses have been approved. The cost, approximately $8 to $10 per application, may prove to be prohibitive for long term therapy.


Various other forms of HIH progesterone have been available for many years. Injectable progesterone in oil has been used to treat secondary amenorrhea, dysfunctional uterine bleeding, and some forms of infertility. The injections are often painful to the patient, for whom long-term therapy may be inconvenient.

'Over-the-Counter Progesterone In the past several years, numerous OTC progesterone creams have become available through health food stores and other retail outlets. However, the types and concentrations of the available progesterone contained in such products vary greatly. Some creams marketed as progesterone contain no active drug, only the herbal precursor’s sarsasapogenin and diosgenin. The body cannot use these sterols in the same manner as progesterone and they have negligible value. Several national assay laboratories offer impartial analyses of such products. In the past several years, numerous OTC progesterone creams have become available through health food stores and other retail outlets. However, the types and concentrations of the available progesterone contained in such products vary greatly. Some creams marketed as progesterone contain no active drug, only the herbal precursors sarsasapogenin and diosgenin. The body cannot use these sterols in the same manner as progesterone and they have negligible value. Several national assay laboratories offer impartial analyses of such products.

Patients who are prone to self-treat with these products should be advised that the progesterone in many of these products is in far lower concentrations than that in prescription drugs. As a result, the patient is likely to receive a subclinical dose and erroneously conclude that progesterone is ineffective.7,21-23

Clinical Use of Micronized Progesterone Patients often complain of unacceptable adverse effects from synthetic progestins that cause them to stop taking the prescribed regimen. Patients may discontinue the medication prematurely or, if they are taking HRT, start to take estrogen alone, which may potentially lead to additional problems MP appears to have a wide safety margin and is not considered teratogenic. It has been approved in vaginal gel form for use in early pregnancy. Although


prospective studies continue, it is generally presumed that MP does not induce any adverse long-term problems. Common adverse effects include mild sedation or drowsiness, especially if the drug is taken with food that enhances absorption. The potential for a toxic reaction to the drug is slight. Current contraindications include liver dysfunction, known or suspected carcinoma, undiagnosed genital bleeding, and thromboembolic disorders. Because peanut oil is the carrier agent, women who are allergic to peanuts should not take MP. MP and MPA are similar in cost when taken once daily. New Options MP offers a new women's health care alternative that appears to be safe, welltolerated, and cost-effective. Because of its human-identical structure, MP should not cause problems associated with synthetic agents. MP is likely to become firstline therapy for the treatment of many gynecologic concerns.


Company: Approval

Status: Berlex Approved

Laboratories May 2001

Treatment for: Contraception Areas: Endocrinology; Obstetrics/Gynecology Yasmin (drospirenone/ethinyl estradiol) has been approved by the FDA for the prevention of pregnancy in women who elect to use an oral contraceptive. Yasmin is a low-dose, monophasic oral contraceptive that contains the unique progestin, drospirenone. Drospirenone, an analogue of spironolactone, differs from progestins currently available in other oral contraceptives by exhibiting both antimineralocorticoid and antiandrogenic effects. Yasmin combines this unique progestin with ethinyl estradiol. Clinical Results The effectiveness and safety of Yasmin was established in large-scale clinical trials of up to two years duration. These trials included 2,629 women who completed 33,160 cycles of use without any other contraception. The mean age of the subjects was 25.5 ± 4.7 years, and the age range was 16-37 years. Results showed that Yasmin provided cycle control with a low rate of spotting and breakthrough


bleeding. The drug proved more than 99% effective in preventing pregnancy, with only one pregnancy occurring in 3,201 cycles of 326 Yasmin users. Side Effects Drospirenone exhibits antimineralocorticoid activity that influences the regulation of water and electrolyte balance in the body. Because this activity may increase potassium levels, Yasmin should not be used by women with kidney, liver or adrenal disease. The following list includes, but is not limited to, the most common adverse events reported with Yasmin use during clinical trials (occuring in greater than 1% of subjects, and which may or may not be drug related):
• • • • • • • • • • • • • • • • •

Headache Breast pain Abdominal pain Nausea Flu syndrome Acne Depression Diarrhea Dysmenorrhea (pain during menstruation) Back pain Infection Dizziness Nervousness Vaginitis Sinusitis Urinary tract infection Rash

In general, the following adverse reactions have been reported in patients receiving oral contraceptives and are believed to be drug related:
• • • • •

Nausea Vomiting Bleeding between menstrual periods Weight gain Breast tenderness


Intolerance to contact lenses

Mechanism of Action Combination oral contraceptives (COCs) act by the suppression of gonadotropins. Although the primary mechanism of this action is inhibition of ovulation, other alterations include changes in the cervical mucus (which increases the difficulty of sperm entry into the uterus) and the endometrium (which reduces the likelihood of implantation). Drospirenone is a spironolactone analogue with antimineralocorticoid activity. Preclinical studies in animals and in vitro have shown that drospirenone has no androgenic, estrogenic, glucocorticoid and antiglucocorticoid activity. Preclinical studies in animals have also shown that drospirenone has antiandrogenic activity. (from Yasmin Prescribing Information) YAMINI – • Yamini, a combination of 0.030 mcg of Ethinyl Estradiol and 3 mg Drospirenone is a new combined oral contraception. • Besides contraception, it offers other welcome benefits. • Yamini is the new low dose pill that may offer more than reliable contraception. • Like other combined pills Yamini contains two hormones, estrogen and progestogen. • It’s different because it contains the progestogen Drospirenone – as close to natural progesterone one can get. So there are welcome advantages.


Drospirenone and ethinyl estradiol
• The general informationwhich should know about drospirenone and
ethinyl estradiol This medication can cause birth defects in an unborn baby. Do not use if you are pregnant. Do not use this medication if you have any of the following conditions: a history of stroke or blood clot, circulation problems (especially if caused by diabetes), a heart valve disorder, breast or uterine cancer, abnormal vaginal bleeding, kidney


or liver disease, an adrenal gland disorder, severe high blood pressure, migraine headaches, or a history of jaundice caused by birth control pills.

• Drospirenone and Ethinyl Estradiol are basically Drospirenone and ethinyl estradiol prevent ovulation (the release of an egg from an ovary) and also cause changes in your cervical and uterine lining, making it harder for sperm to reach the uterus and harder for a fertilized egg to attach to the uterus. The combination of drospirenone and ethinyl estradiol is used as contraception to prevent pregnancy. It is also used to treat moderate acne in women who are at least 14 years old and have started having menstrual periods, and who wish to use birth control pills to prevent pregnancy. This medication is also used to treat the symptoms of premenstrual dysphoric disorder (PMDD), such as anxiety, depression, irritability, trouble concentrating, lack of energy, sleep or appetite changes, breast tenderness, joint or muscle pain, headache, and weight gain. Drospirenone and ethinyl estradiol may also be used for other purposes not listed in this medication guide. FDA pregnancy category X. This medication can cause birth defects. Do not use this medication if you are pregnant. Tell your doctor right away if you become pregnant during treatment. The hormones in this medication can pass into breast milk and may harm a nursing baby. This medication may also slow breast milk production. Do not use if you are breast-feeding a baby. Drospirenone may raise potassium levels in your blood. Other medical conditions


can also affect potassium levels, including liver disease, kidney disease, and adrenal gland disorders. Before using drospirenone and ethinyl estradiol, tell your doctor if you have any of these conditions.

• Drospirenone and Ethinyl Estradiol should be taken as Take this medication exactly as it was prescribed for you. Do not take larger amounts, or take it for longer than recommended by your doctor. You will take your first pill on the first day of your period or on the first Sunday after your period begins (follow your doctor's instructions). Take one pill every day, no more than 24 hours apart. When the pills run out, start a new pack the following day. Get your prescription refilled before you run out of pills completely.

If a single dose will be missed then-

Missing a pill increases your risk of becoming pregnant. If you miss one"active" pill, take the dose as soon as you remember or take two pills at the time of your next regularly scheduled dose. You do not need to use backup birth control. If you miss two"active" tablets in a row in week one or two, take two tablets each for the next two regularly scheduled doses (one missed tablet plus one regularly scheduled tablet for 2 days in a row). Use another form of birth control for at least 7 days following the missed tablets. If you miss two "active" tablets in a row in week three, or if you miss three tablets in a row during any of the first 3 weeks, throw out the rest of the pack


and start a new package on the same day if you are a Day 1 starter. If you are a Sunday starter, keep taking a pill every day until Sunday. On Sunday, throw out the rest of the pack and start a new pack of pills that same day. You may not have a period that month, but this is expected. However, if you miss your period 2 months in a row, call your doctor because you might be pregnant. If you miss one of the reminder pills in week four, skip that dose and take the next one as directed. If you miss a pill, you may become pregnant if you have sex in the 7 days after your missed pill. You MUST use another birth control method (such as condoms or spermicides) as a back-up for those 7 days.

The overdose of this drug can lead to –

Seek emergency medical attention if you think you have used too much of this medicine. Overdose symptoms may include nausea, vomiting, or vaginal bleeding.

• The things which should be avoided while taking drospirenone and
ethinyl estradiol -


Do not smoke while using this medication, especially if you are older than 35. Smoking can increase your risk of blood clots, stroke, or heart attack caused by birth control pills. Drospirenone and ethinyl estradiol will not protect you from sexually transmitted diseases--including HIV and AIDS. Using a condom is the only way to protect yourself from these diseases.

• The possible side effects of drospirenone and ethinyl estradiol Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat. Stop using this medication and call your doctor at once if you have any of these serious side effects:

sudden numbness or weakness, confusion, pain behind the eyes, problems

with vision, speech, or balance;

chest pain or heavy feeling, pain spreading to the arm or shoulder, nausea,

sweating, general ill feeling;
   

a change in the pattern or severity of migraine headaches; stomach pain, loss of appetite, jaundice (yellowing of the skin or eyes); a breast lump; or symptoms of depression (sleep problems, weakness, mood changes).

Less serious side effects may include:

breast pain, tenderness, or swelling;


freckles or darkening of facial skin, increased hair growth, or loss of scalp

   

changes in weight or appetite, swelling of your hands or feet; problems with contact lenses; vaginal itching or discharge; or changes in your menstrual periods.

This is not a complete list of side effects and others may occur. Tell your doctor about any unusual or bothersome side effect.

• The other drugs which can be lessen the affect drospirenone and ethinyl
estradiolSome drugs can make drospirenone and ethinyl estradiol less effective, which may result in pregnancy. Other drugs may be affected by drospirenone and ethinyl estradiol. Before using this medication, tell your doctor about all the prescription and over-the-counter medications you use. This includes vitamins, minerals, herbal products, and drugs prescribed by other doctors. Do not start using a new medication without telling your doctor.

Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed. Every effort has been made to ensure that the information provided by Cerner Multum, Inc. ('Multum') is accurate, up-to-date, and complete, but no guarantee is


made to that effect. Drug information contained herein may be time sensitive. Multum information has been compiled for use by healthcare practitioners and consumers in the United States and therefore Multum does not warrant that uses outside of the United States are appropriate, unless specifically indicated otherwise. Multum's drug information does not endorse drugs, diagnose patients or recommend therapy. Multum's drug information is an informational resource designed to assist licensed healthcare practitioners in caring for their patients and/or to serve consumers viewing this service as a supplement to, and not a substitute for, the expertise, skill, knowledge and judgment of healthcare practitioners. The absence of a warning for a given drug or drug combination in no way should be construed to indicate that the drug or drug combination is safe, effective or appropriate for any given patient. Multum does not assume any responsibility for any aspect of healthcare administered with the aid of information Multum provides. The information contained herein is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. If you have questions about the drugs you are taking, check with your doctor, nurse or pharmacist.


Drug Forms:
• •

Drospirenone; Ethinyl Estradiol tablets (below) Drospirenone, Ethinyl Estradiol Oral tablet, Inert Oral tablet Español:

• •

Tabletas de drospirenona; etinil-estradiol Drospirenona; Etinil-Estradiol Tableta oral, Tableta inerte oral


Drospirenone; Ethinyl Estradiol tablets

Drospirenone; Ethinyl Estradiol tablets are -

DROSPIRENONE; ETHINYL ESTRADIOL (Yasmin®,Yamini) is an oral contraceptive (birth control pill or "the pill"). This product combines an estrogen and progestin, similar to the natural sex hormones (estrogen and progesterone) produced in a woman's body. Ethinyl estradiol is the estrogen and drospirenone is the progestin. This product can prevent ovulation and pregnancy. In general, a combination of estrogen and progestin works better than a single-ingredient product. Drospirenone; ethinyl estradiol tablets can also help regulate menstrual flow, treat acne or may be used for other hormone-related problems in females. A generic product is not available for this birth control pill.

We should tell our health care provider these things before taking this medicine

They need to know if you have or ever had any of these conditions: • adrenal gland disease • blood clots • blood sugar problems, like diabetes • cancer of the breast, cervix, ovary, uterus, vagina, or unusual vaginal bleeding that has not been evaluated by a health care professional • depression • fibroids • gallbladder disease • heart or circulation problems • high blood pressure • high potassium level • kidney disease • jaundice • liver disease • menstrual problems • migraine headaches • stroke • systemic lupus erythematosus (SLE) • tobacco smoker • an unusual or allergic reaction to estrogen/progestin, other hormones, medicines, foods, dyes, or preservatives


• pregnant or trying to get pregnant. • breast-feeding This medicine should be taken likeTake drospirenone; ethinyl estradiol pills by mouth. Before you start taking these pills decide what is a suitable time of day and always take them at the same time of day in the order directed on the pack. Swallow the pills with a drink of water. Take with food to reduce stomach upset. Do not take more often than directed. Most products contain a 21-day supply of pills containing the active ingredients. An additional 7 pills containing inactive ingredients may be included and are to be taken during the week of menstruation; this reduces the chance of missing the first day of the next cycle. Most products are to be started on the first Sunday after you start your period or on the first day of your period. You may need to ask your health care provider which day you should start your packet. Before starting this medication, read the paper on your prescription provided by your pharmacist. This paper will tell you about the specific product you are taking. Make certain you understand the instructions. Keep an extra month's supply of your pills available to ensure that you will not miss the first day of the next cycle. Contact your pediatrician or health care professional regarding the use of this medicine in children. Special care may be needed.

The possible side effects from taking drospirenone; ethinyl estradiol are -

Severe side effects are relatively rare in women who are healthy and do not smoke while they are taking oral contraceptives. On average, more women have problems due to complications from getting pregnant than have problems with oral contraceptives. Many of the minor side effects may go away as your body adjusts to the medicine. However, the potential for severe side effects does exist and you may want to discuss these with your health care provider. The following symptoms or side effects may be related to blood clots and require immediate medical or emergency help:

• chest pain • coughing up blood • dizziness or fainting spells • leg, arm or groin pain • severe or sudden headaches • stomach pain (severe) • sudden shortness of breath • sudden loss of coordination, especially on one side of the body • swelling of the hands, feet or ankles, or rapid weight gain • vision or speech problems • weakness or numbness in the arms or legs, especially on one side of the body Other serious side effects are rare. Contact your health care provider as soon as you can if the following side effects occur: • breast tissue changes or discharge • changes in vaginal bleeding during your period or between your periods • headaches or migraines • increases in blood sugar, especially if you have diabetes • increases in blood pressure, especially if you are known to have high blood pressure • symptoms of vaginal infection (itching, irritation or unusual discharge) • tenderness in the upper abdomen • vomiting • yellowing of the eyes or skin Side effects that usually do not require medical attention (report to your health care provider if they continue or are bothersome): • breakthrough bleeding and spotting that continues beyond the 3 initial cycles of pills • breast tenderness • mild stomach upset • mood changes, anxiety, depression, frustration, anger, or emotional outbursts • increased or decreased appetite • increased sensitivity to sun or ultraviolet light • nausea • skin rash, acne, or brown spots on the skin • tiredness • weight gain (slight).


Infertility is the failure of a couple to become pregnant after one year of regular, unprotected intercourse. In both men and women the fertility process is complex. Infertility affects about 10% of all couples. Even under ideal circumstances, the probability that a woman will get pregnant during a single menstrual cycle is only about 30%. And, when conception does occur, only 50 - 60% of pregnancies advance beyond the 20th week. (The inability of a woman to produce a live birth because of abnormalities that cause miscarriages is called infecundity and is not discussed in detail in this report.) About a third of infertility problems are due to female infertility, and another third are due to male infertility. In the remaining cases, infertility affects both partners or the cause is unclear. Although this report specifically addresses infertility in women, it is equally important for the male partner to be tested at the same time.] The Female Reproductive System The primary organs and structures in the reproductive system are: The uterus is a pear-shaped organ located between the bladder and lower intestine. It consists of two parts, the body and the cervix. • When a woman is not pregnant the body of the uterus is about the size of a fist, with its walls collapsed and flattened against each other. During pregnancy the walls of the uterus are pushed apart as the fetus grows. • The cervix is the lower portion of the uterus. It has a canal opening into the vagina with an opening called the os, which allows menstrual blood to flow out of the uterus into the vagina. • Leading off each side of the body of the uterus are two tubes known as the fallopian tubes. Near the end of each tube is an ovary. • Ovaries are egg-producing organs that hold 200,000 - 400,000 follicles (from folliculus, meaning "sack" in Latin). These cellular sacks contain the materials needed to produce ripened eggs, or ova.


The inner lining of the uterus is called the endometrium. During pregnancy, it thickens and becomes enriched with blood vessels to house and support the growing fetus. If pregnancy does not occur, the endometrium is shed as part of the menstrual flow. Menstrual flow also consists of blood and mucus from the cervix and vagina.

Reproductive Hormones. The hypothalamus (an area in the brain) and the pituitary gland regulate the reproductive hormones. The pituitary gland is often referred to as the master gland because of its important role in many vital functions, many of which require hormones. In women, six key hormones serve as chemical messengers that regulate the reproductive system: The hypothalamus first releases the gonadotropin-releasing hormone (GnRH). • This chemical, in turn, stimulates the pituitary gland to produce folliclestimulating hormone (FSH) and luteinizing hormone (LH).

Estrogen, progesterone, and the male hormone testosterone are secreted by the ovaries at the command of FSH and LH and complete the hormonal group necessary for reproductive health.


Ovulation. The process leading to fertility is very intricate. It depends on the healthy interaction of the reproductive organs and hormone systems in both the male and female. In addition, reproduction is limited by the phases of female fertility. Nevertheless, this process results in conception within a year for about 80% of couples. Only 15% conceive within a month of their first attempts, however, and about 60% succeed after 6 months. A woman's ability to produce children occurs after she enters puberty and begins to menstruate. The process of conception is complex: With the start of each menstrual cycle, follicle-stimulating hormone (FSH) stimulates several follicles to mature over a 2-week period until their eggs nearly triple in size. Only one follicle becomes dominant, however, during a cycle. • FSH signals this dominant follicle to produce estrogen, which enters the bloodstream and reaches the uterus. There, estrogen stimulates the cells in the uterine lining to reproduce, therefore thickening the walls. • Estrogen levels reach their peak around the 14th day of the cycle (counting days beginning with the first day of a period). At that time, they trigger a surge of luteinizing hormone (LH).

LH serves two important roles: First, the LH surge around the 14th cycle day stimulates ovulation. It does this by causing the dominant follicle to burst and release its egg into one of the two fallopian tubes. Once in the fallopian tube, the egg is in place for fertilization. • Next, LH causes the ruptured follicle to develop into the corpus luteum. The corpus luteum provides a source of estrogen and progesterone during pregnancy.

Click the icon to see an image of the corpus luteum. Fertilization. The so-called "fertile window" is 6 days long and starts 5 days before ovulation and ends the day of ovulation. Fertilization occurs as follows:

The sperm can survive for up to 3 days once it enters the fallopian tube. The egg survives 12 - 24 hours unless it is fertilized by a sperm. • If the egg is fertilized, about 2 - 4 days later it moves from the fallopian tube into the uterus where it is implanted in the uterine lining and begins its 9-month incubation. • The placenta forms at the site of the implantation. The placenta is a thick blanket of blood vessels that nourishes the fertilized egg as it develops.

The corpus luteum (the yellow tissue formed from the ruptured follicle) continues to produce estrogen and progesterone during pregnancy. If the egg is not fertilized, the corpus luteum degenerates into a form called the corpus albicans, and estrogen and progesterone levels drop. Finally, the endometrial lining sloughs off and is shed during menstruation.

Typical Menstrual Cycle

Menstrual Phases

Typical No. of Days

Hormonal Actions

Follicular Cycle Days 1 - 6: Estrogen and progesterone start (Proliferative) Phase Beginning of out at their lowest levels. menstruation to end of FSH levels rise to stimulate blood flow. maturity of follicles. Ovaries start


producing estrogen and levels rise, while progesterone remains low.

Cycle Days 7 - 13: The endometrium (the inner lining of the uterus) thickens to prepare for the egg implantation.


Cycle Day 14:

Surge in LH. Largest follicle bursts and releases egg into fallopian tube.

Luteal (Secretory) Cycle Days 15 - 28: Phase, also known as the Premenstrual Phase

Ruptured follicle develops into corpus luteum, which produces progesterone. Progesterone and estrogen stimulate blanket of blood vessels to prepare for egg implantation.

If fertilization occurs:

Fertilized egg attaches to blanket of blood vessels that supplies nutrients for the developing placenta. Corpus luteum continues to produce estrogen and progesterone.


If fertilization does not Corpus luteum deteriorates. occur: Estrogen and progesterone levels drop. The blood vessel lining sloughs off and menstruation begins.

Risk Factors In the U.S., about 10% of women ages 15 - 44, or about 6.1 million women, have problems getting pregnant or carrying a baby to term. Age Fertility declines as a woman ages. Fertility begins to decline when a woman reaches her mid-30s, and rapidly declines after her late 30s. As a woman ages, her ovaries produce fewer eggs. In addition, the quality of the eggs is poorer than those of younger women. Older women have a higher risk for eggs with chromosomal abnormalities, which increase the risk for miscarriage and birth defects. Older women are also more likely to have health problems that may interfere with fertility. Weight Although most of a woman's estrogen is manufactured in her ovaries, 30% is produced in fat cells by a process that transforms circulating adrenal male hormones into estrogen. Because a normal hormonal balance is essential for the process of conception, extreme weight levels (either high or low) can contribute to infertility. Being Overweight. Being overweight or obese (fat levels that are 10 - 15% above normal) can contribute to infertility in various ways. Obesity is also associated with polycystic ovarian syndrome (PCOS), an endocrinologic disorder that can cause infertility.

Being Underweight. Body fat levels 10 - 15% below normal can completely shut down the reproductive process. Women at risk include: Women with eating disorders, such as anorexia or bulimia. • Women on very low-calorie or restrictive diets are at risk, especially if their periods are irregular. • Strict vegetarians might have difficulties if they lack important nutrients, such as vitamin B12, zinc, iron, and folic acid. • Marathon runners, dancers, and others who exercise very intensely.

Smoking Cigarette smoking can harm a womens ovaries and contribute to a decrease in eggs. Studies show that women who smoke are more likely to reach menopause earlier than women who do not smoke. Alcohol and Caffeine Use Alcohol and caffeine use may contribute to infertility. Environmental Factors Exposure to environmental hazards (herbicides, pesticides, industrial solvents) may affect fertility. Estrogen-like hormone-disrupting chemicals are of particular concern for infertility in men and for effects on offspring of women. Phthalates, chemicals used to soften plastics, are under particular scrutiny for their ability to disrupt hormones. Stress and Fertility Neurotransmitters (chemical messengers) act in the hypothalamus gland, which controls both reproductive and stress hormones. Severely elevated levels of stress hormone can, in fact, shut down menstruation. Whether stress has any significant effect on fertility or fertility treatments is unclear.


Causes Numerous medical conditions can contribute to infertility. In fact, most cases of infertility are due to other medical conditions. These disorders can damage the fallopian tubes, interfere with ovulation, or cause hormonal complications. Some of the main medical conditions associated with infertility follow. Pelvic Inflammatory Disease Pelvic inflammatory disease (PID) is a major cause of female infertility worldwide. PID comprises a variety of infections caused by different bacteria that affect the reproductive organs, appendix, and parts of the intestine that lie in the pelvic area. The sites of infection most often implicated in infertility are in the fallopian tubes, a specific condition referred to as salpingitis. Causes of PID. PID may result from many different conditions that cause infections. Among them are: Sexually transmitted diseases (cause of most PID). Chlamydia trachomatis is an infectious organism that causes 75% of infertility in the fallopian tubes. Gonorrhea is responsible for most of the remaining cases. • Pelvic tuberculosis • Nonsterile abortions • Ruptured appendix

Effects of PID. Severe or frequent attacks of PID can eventually cause scarring, abscess formation, and tubal damage that result in infertility. About 20% of women who develop symptomatic PID become infertile. PID also significantly increases the risk of ectopic pregnancy (fertilization in the fallopian tubes). The severity of the infection, not the number of the infections, appears to pose the greater risk for infertility.

Endometriosis Endometriosis may account for as many as 30% of infertility cases. Endometriosis rarely causes an absolute inability to conceive, but, nevertheless, it can contribute to it both directly and indirectly.

Endometriosis is a noncancerous condition in which cells that normally line the uterus (endometrium) also grow on other areas of the body, causing pain and irregular bleeding. Endometrial cysts may cause infertility in several ways: If implants occur in the fallopian tubes, they may block the egg's passage. • Implants that occur in the ovaries prevent the release of the egg. • Severe endometriosis can eventually form rigid webs of scar tissue (adhesions) between the uterus, ovaries, and fallopian tubes, thereby preventing the transfer of the egg to the tube.

Polycystic Ovarian Syndrome Polycystic ovarian syndrome (PCOS) is a condition in which the ovaries produce high amounts of androgens (male hormones), particularly testosterone. PCOS

occurs in about 6% of women, and amenorrhea or oligomenorrhea (infrequent menses) is quite common.

Click the icon to see an image of polycystic ovarian syndrome. In PCOS, increased androgen production produces high luteinizing hormone (LH) levels and low follicle-stimulating hormone (FSH) levels, so that follicles are prevented from producing a mature egg. Without egg production, the follicles swell with fluid and form into cysts. Every time an egg is trapped within the follicle, another cyst forms and the ovary swells, sometimes reaching the size of a grapefruit. Without ovulation, progesterone is no longer produced, whereas estrogen levels remain normal. The elevated levels of androgens (hyperandrogenism) can cause obesity, facial hair, and acne, although not all women with PCOS have such symptoms. PCOS also poses a high risk for insulin resistance, which is associated with type 2 diabetes. About half of PCOS patients also have diabetes. Premature Ovarian Failure (Early Menopause) Premature ovarian failure is the early depletion of follicles before age 40, which, in most cases, leads to premature menopause. It affects about 1% of women and is typically preceded by irregular periods, which might continue for years. In this condition, follicle-stimulating hormone (FSH) levels are elevated, as they are during perimenopause. Premature ovarian failure is a significant cause of infertility, and women who have this condition have only a 5 - 10% chance to conceive without fertility treatments. Causes of premature ovarian failure include:


Adrenal, pituitary, or thyroid gland deficiencies • Genetic disorders, such as Turner syndrome and fragile X syndrome • Cancer treatments (radiation, chemotherapy, or both) • Autoimmune disorders (such as type 1 diabetes, systemic lupus erythematosus, autoimmune hypothyroidism, Addison's disease) are associated with a higher risk for early menopause

Uterine Fibroids Benign fibroid tumors in the uterus are extremely common in women in their 30s. Large fibroids may cause infertility impairing the uterine lining, by blocking the fallopian tube, or by distorting the shape of the uterine cavity or altering the position of the cervix.

Elevated Prolactin Levels (Hyperprolactinemia) Prolactin is a hormone produced in the pituitary gland that stimulates breast development and milk production in association with pregnancy. High levels of prolactin (hyperprolactinemia) reduce gonadotropin hormones and inhibit ovulation. Hyperprolactinemia in women who are not pregnant or nursing can be caused by hypothyroidism or pituitary adenomas. (Pituitary adenomas are benign tumors that secrete prolactin.) Some drugs, including oral contraceptives and some antipsychotic drugs, can also elevate levels of prolactin. Secretions from the breast not related to pregnancy or nursing (called galactorrhea) are a telltale symptom of high prolactin levels and should be investigated. Structural Problems Causing Obstruction


Inborn Abnormalities. Inborn genital tract abnormalities may cause infertility. Mullerian agenesis is a specific malformation in which no vagina or uterus develops. Even in these cases, some women can become mothers by undergoing in vitro fertilization and having the fertilized egg implanted in another woman who is willing and able to carry the pregnancy (a surrogate mother). Uterine or Abdominal Scarring. Bands of scar tissue that bind together after abdominal or pelvic surgery or infection (called adhesions) can restrict the movement of ovaries and fallopian tubes and may cause infertility. Asherman syndrome, for example, is scarring in the uterus that can cause obstructions and secondary amenorrhea. It may be caused by surgery, repeated injury, or unknown factors. Diagnosis In any fertility work-up, both male and female partners are tested if pregnancy fails to occur after a year of regular unprotected sexual intercourse. Fertility testing should especially be performed if a woman is over 35 years old or if either partner has known risk factors for infertility. An analysis of the man's semen should be performed before the female partner undergoes any invasive testing. Medical History and Physical Examination The first step in any infertility work up is a complete medical history and physical examination. Menstrual history, lifestyle issues (smoking, drug and alcohol use, and caffeine consumption), any medications being taken, and a profile of the patient's general medical and emotional health can help the doctor decide on appropriate tests. Easy Preliminary Steps Before embarking on an expensive fertility work-up, the following steps are free or low-cost and can be helpful:


Monitor basal body temperature. This is accurate in determining if ovulation is actually taking place. • Test the consistency of your cervical mucus. Collect some mucus between your two fingers and stretch it apart. If you are near the time of ovulation, the mucus will stretch more than 1 inch before it breaks. As an alternative, at-home kits can test saliva as substitute for checking cervical mucus. • Take an over-the-counter urine test for detecting luteinizing hormone (LH) surges. This helps determine the day of ovulation. Tests are also available to measure levels of follicle-stimulating hormone (FSH). However, these at-home tests may not be as accurate as those performed in a doctors office.

Laboratory Tests Several laboratory tests may be used to detect the cause of infertility and monitor treatments: Hormonal Levels. Blood and urine tests are taken to evaluate hormone levels. Hormonal tests for ovarian reserve (the number of follicles and quality of the eggs) are especially important for older women. Examples of possible results include: High follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels and low estrogen levels suggest premature ovarian failure. • High LH and low FSH may suggest polycystic ovary syndrome or luteal phase defect. • High FSH and high estrogen levels on the third day of the cycle predict poor success rates in older women trying fertility treatments. • LH surges indicate ovulation. • Blood tests for prolactin levels and thyroid function are also measured. These are hormones that may indirectly affect fertility.

Clomiphene Challenge Test. Clomiphene citrate (Clomid, Serophene), a standard fertility drug, may be used to test for ovarian reserve. With this test, the doctor measures FSH on day 3 of the cycle. The woman takes clomiphene orally on days 5 and 9 of the cycle. The doctor measures FSH on the tenth day. High levels of FSH either on day 3 or day 10 indicate a poor chance for a successful outcome.


Tissue Samples. To rule out luteal phase defect, premature ovarian failure, and absence of ovulation, the doctor may take tissue samples of the uterus 1 - 2 days before a period to determine if the corpus luteum is adequately producing progesterone. Tissue samples taken from the cervix may be cultured to rule out infection. Tests for Autoimmune Disease. Tests for autoimmune disease, such as hypothyroidism and diabetes, should be considered in women with recent ovarian failure that is not caused by genetic abnormalities. Imaging Tests and Diagnostic Procedures If an initial fertility work-up does not reveal abnormalities, more extensive tests may help reveal abnormal tubal or uterine findings. The four major approaches for examining the uterus and fallopian tubes are: Ultrasound (particularly sonohysterography) • Hysterosalpingography • Hysteroscopy • Laparoscopy





Combinations of these imaging procedures may be used to confirm diagnoses. Ultrasound and Sonohysterography. Ultrasound is the standard imaging technique for evaluating the uterus and ovaries, detecting fibroids, ovarian cysts and tumors, and also obstructions in the urinary tract. It uses sound waves to produce an image of the organs and entails no risk and very little discomfort. Transvaginal sonohysterography uses ultrasound along with saline infused into the uterus, which enhances the visualization of the uterus. This technique is proving to be more accurate than standard ultrasound in identifying potential problems. It is currently the gold standard for diagnosing polycystic ovaries. Hysteroscopy. Hysteroscopy is a procedure that may be used to detect the presence of endometriosis, fibroids, polyps, pelvic scar tissue, and blockage at the ends of

the fallopian tubes. Some of these conditions can be corrected during the procedure by cutting away any scar tissue that may be binding organs together or by destroying endometrial implants. Hysteroscopy may be done in a doctors office or in an operating room, depending on the type of anesthesia used. The procedure uses a long flexible or rigid tube called a hysteroscope, which is inserted into the vagina and through the cervix to reach the uterus. A fiber optic light source and a tiny camera in the tube allow the doctor to view the cavity. The uterus is filled with saline or carbon dioxide to inflate the cavity and provide better viewing. This frequently causes cramping. There are small risks of bleeding, infection, and reactions to anesthesia. Many patients experience temporary discomfort in the shoulders after the operation due to residual carbon dioxide that puts pressure on the diaphragm. The wound itself is minimally painful. Hysterosalpingography. Hysterosalpingography is performed to discover possible blockage in the fallopian tubes and abnormalities in the uterus: The doctor inserts a tube into the cervix through which a special dye is injected. (The patient may experience some cramping and discomfort.) • The dye passes into the uterus and up through the fallopian tubes. • An x-ray is taken of the dye-filled uterus and tubes. • If the dye is seen emerging from the end of the tube, no blockage is present. (In some cases, hysterosalpingography may even restore fertility by clearing away tiny tubal blockages.) • If results show blockage or abnormalities, the test may need to be repeated. In case of blockage, hysterosalpingography may reveal a number of conditions, including endometrial polyps, fibroid tumors, or structural abnormalities of the uterus and tubes.

There is a small risk of pelvic infection, and antibiotics may be prescribed prior to the procedure. Laparoscopy. Laparoscopy is a minimally invasive surgical procedure. It requires general anesthesia and is performed in an operating room. The surgeon makes a


very small incision below the belly button and inserts an instrument called a laparoscope, which is similar to a hysteroscope. (The difference is that a laparoscope is inserted through the abdomen, while a hysteroscope is inserted through the cervix.) Through the laparoscope, the surgeon can view the uterus, fallopian tube, and ovaries. Laparoscopy is most helpful for identifying endometriosis or other adhesions that may affect fertility. Treatment Treatment for infertility should first address any underlying medical condition that may be contributing to fertility problems. Drugs, surgery, or both may be used to treat these conditions. Surgery may also be used to repair blockage in fallopian tubes. Fertility Treatment Approaches Several approaches are used to treat infertility: Lifestyle measures (healthy lifestyle, planning sexual activity with ovulation cycle, managing stress and emotions) • Drugs to induce ovulation, such as clomiphene and gonadotrophins • Assisted reproductive technologies (ART) such as in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI)

Choosing a Fertility Clinic Some doctors recommend that if a couple fails to conceive after 1 - 2 years of frequent unprotected sex, they should consult a fertility expert. Women who are 35 or older, however, may want to begin exploring their options if they do not become pregnant within 6 months to a year. Choosing a good fertility clinic is important. Those offering assisted reproductive techniques are not always regulated by the government, and abuses have been reported, including lack of informed consent, unauthorized use of embryos, and failure to routinely screen donors for disease.


The clinic should always provide the following information: The live-birth rate (not just pregnancy success rate) for other couples with similar infertility problems. (Multiple births, such as twins or triplets, are counted as one live birth.) • Such statistics should include high-risk women, such as those who are older or fail to produce eggs. (Some disreputable clinics give success percentages that exclude high-risk women from their total, thereby making the percentage of success much higher.)

Advanced fertility procedures and medications are extremely expensive and often not covered by insurance. Couples should be cautious about offers of rebates in the event of failure; the clinics offering them are often significantly more expensive than those that don't offer such gimmicks. Special Considerations for Patients with Cancer Women who are undergoing cancer treatments and who want to become pregnant should see a reproductive specialist to discuss their options. According to the American Society of Clinical Oncology's guidelines, the fertility preservation method with the best chance of success is embryo cryopreservation. This procedure involves harvesting a woman's eggs (oocytes), followed by in vitro fertilization and freezing of embryos for later use. Other treatments under investigation include egg preservation, collecting and freezing unfertilized eggs, removing and freezing a part of the ovary for later reimplantation, and using hormone therapy to protect the ovaries during chemotherapy. Women may be able to access these investigational approaches through enrolling in clinical trials. Lifestyle Changes Although there are no dietary or nutritional cures for infertility, a healthy lifestyle is important. Some ovulatory problems may be reversible by changing behavioral patterns. Some tips include:


Maintain a healthy weight. Women who are either over- or underweight are at risk for fertility failure, including a lower chance for achieving success with fertility procedures. • Stop smoking. Smoking may increase the risk for infertility in both men and women. Everyone should quit. • Avoid excessive exercise if it causes menstrual irregularity. However, moderate and regular exercise is essential for good health. • Avoid or limit caffeine and alcohol. • Avoid any unnecessary medications.

Planning Sexual Activity and Monitoring Basal Body Temperature Both male and female hormone levels fluctuate according to the time of day, and they vary from day to day, month to month, and seasonally. Some timing tips might be helpful. Monitoring Basal Body Temperature. To determine the most likely time of ovulation and therefore the time of fertility, a woman is instructed to take her body temperature, called her basal body temperature. This is the body's temperature as it rises and falls in accord with hormonal fluctuations. Each morning before rising, the woman takes her temperature with a specialized basal body thermometer and marks the result on a graph-paper chart. • The woman also notes the days of menstruation and sexual activity. • The so-called "fertile window" is 6 days long, starts 5 days before ovulation, and ends the day of ovulation. • The chances for fertility are considered to be highest between days 10 and 17 in the menstrual cycle (with day 1 being the first day of the period, and ovulation occurring about 2 weeks later). However, cycles vary from woman to woman. • Immediately after ovulation the body temperature increases sharply in about 80% of cases. (Some women can be ovulating normally yet not show this temperature pattern.)

By studying the temperature patterns after a few months, couples can begin to anticipate ovulation and plan their sexual activity accordingly. Couples must try to avoid becoming fixated on the chart, however, in scheduling their sexual activity. Spontaneity can be lost, and the stress on the relationship can be quite severe.

Frequency of Intercourse. The question of how often a couple should have intercourse is in debate. Some doctors say that having sex more than 2 days a week adds no benefits. Moreover, frequent sexual activity lowers sperm count per ejaculation. Other studies have indicated, however, that having intercourse every day, or even several times a day, before and during ovulation, improves pregnancy rates. Although sperm count per ejaculation is low, a constantly replenished semen supply is more likely to result in a fertilized egg. Dealing with Stress The fertility treatment process presents a roller coaster of emotions. There are almost no sure ways to predict which couples will eventually conceive. Some couples with multiple problems will overcome great odds, while other, seemingly fertile, couples fail to conceive. Many of the new treatments are remarkable, but a live birth is never guaranteed. The emotional burden on the couple is considerable, and some planning is helpful. Decide in advance how many and what kind of procedures will be emotionally and financially acceptable and attempt to determine a final limit. Fertility treatments are expensive. A successful pregnancy often depends on repeated attempts. • Prepare for multiple births as a possible outcome for successful pregnancy (especially if assisted reproductive technologies are used). A pregnancy that results in a multiple birth introduces new complexities and emotional problems • Determine alternatives (adoption, donor sperm or egg, or having no children) as early as possible in the fertility process. This can reduce anxiety during treatments and feelings of hopelessness in case conception does not occur.

Medications Fertility drugs are often used alone as initial treatment to induce ovulation. If they fail as sole therapy, they may be used with assisted reproductive procedures, such as in vitro infertilization, to produce multiple eggs, a process called superovulation.


According to the American Society for Reproductive Medicine, fertility drugs can be divided into three main categories: Medications for Ovarian Stimulation. Clomiphene (Clomid, Serophene); letrozole(Femara), follicle stimulating hormone (FSH) [Follistim, Gonal-F, Bravelle]; human menopausal gonadotrophin (hMG) [Humegon, Repronex, Menopur); luteneizing hormone (LH) [Luveris] • Medications for Oocyte Maturation. Human chorionic gonadotropin(hCG) [Profasi, APL, Pregnyl, Novarel, Ovidrel) • Medications to Prevent Premature Ovulation. GnRh agonists (Lupron and Synarel); Gn RH antagonists (Antagon, Cetrotide).

Clomiphene Clomiphene citrate (Clomid, Serophene) is usually the first fertility drug of choice for women with infrequent periods and long menstrual cycles. Unlike more potent drugs used in superovulation, clomiphene is gentler and works by blocking estrogen, which tricks the pituitary into producing follicle-stimulating hormone (FSH) and luteinizing hormone (LH). This boosts follicle growth and the release of the egg. Clomiphene can be taken orally, is relatively inexpensive, and the risk for multiple births (about 5%, mostly twins) is lower than with other drugs. Women with the best chances for success with this drug are those who have the following conditions:
• •

Polycystic ovarian syndrome (PCOS) Ability to menstruate but irregular menstrual cycle

Women with poorer chances of success with this drug have the following conditions:
• • •

Infertility but with normal ovulation Low estrogen levels Premature ovarian failure (early menopause)

One or two tablets are taken each day for 5 days, usually starting 2 - 5 days after the period starts. If successful, ovulation occurs about a week after the last pill has

been taken. If ovulation does not occur, then a higher dose may be given for the next cycle. If this regimen is not successful, treatment may be prolonged or additional drugs may be added. Doctors usually do not recommend more than 6 cycles. Clomiphene often reduces the amount and quality of cervical mucus and may cause thinning of the uterine lining. In such cases, other hormonal drugs may be given to restore thickness. Other side effects of clomiphene include ovarian cysts, hot flashes, nausea, headaches, weight gain, and fatigue. There is a 5% chance of having twins with this drug, and a slightly increased risk for miscarriage. Gonadotropins If clomiphene does not work or is not an appropriate choice, gonadotropin drugs are a second option. Gonadotropins include several different types of drugs that contain either a combination of follicle-stimulating hormone (FSH) and luteinizing hormone (LH), or only FSH. Whereas clomiphene works indirectly by stimulating the pituitary gland to secrete FSH, (which prompts follicle production), gonadtropin hormones directly stimulate the ovaries to produce multiple follicles. Gonadotropins are given by injection. (Your doctor may show you how to selfadminister the injection.) Gonadotropins include: Human Menopausal Gonadtropins (hMG), also called menotropins • Human Chorionic Gonadotropins (hCG) • Follicle Stimulating Hormone (FSH) • Gonadotropin-releasing hormone (GnRH) analogs, which include GnRH agonists and GnRH antagonists

Gonadotropin drugs are either natural compounds extracted from urine or synthetic compounds that are genetically engineered in a laboratory using recombinant DNA. Human Menopausal Gonadotropin (hMG). HMG drugs, also called menotropins, contain a mixture of both FSH and LH. These drugs (Menopur, Repronex,


Humegon) are all derived from the urine of postmenopausal women. HMG is administered as a series of injections 2 - 3 days after the period starts. Injections are usually given for 7 - 12 days, but the time may be extended if ovulation does not occur. In such cases, a shot of human chorionic gonadotropin (hCG) may trigger ovulation. Human Chorionic Gonadotropin (hCG). Human chorionic gonadotropin (hCG) is similar to LH. It mimics the LH surge, which stimulates the follicle to release the egg. Natural hCG drugs, derived from the urine of pregnant women, include Pregnyl, Profasi, Novarel, and APL. Ovidrel is the only available genetically modified hCG drug. Ovidrel has fewer side effects at the injection site, and its quality can be better controlled than the natural drugs. It is generally used after hMG or FSH to stimulate the final maturation stages of the follicles. Ovulation, if it occurs, does so about 36 - 72 hours after administration. Follicle Stimulating Hormone (FSH). Urofollitropin (Bravelle, Fertinex) is a purified form of FSH, derived from the urine of postmenopausal women. Follitropin drugs (Gonal-F, Follistim) are synthetic versions of FSH. These FSH drugs are sometimes given in combination with an hCG drug. GnRH Analogs (Agonists or Antagonists). Gonadotropin-releasing hormone (GnRH) is a hormone produced in the hypothalamus part of the brain. GnRH stimulates the pituitary gland to produce LH and FSH. GnRH analogs are synthetic drugs that are classified as either agonists or antagonists. They are similar to natural GnRH but have very different actions. While natural GnRH stimulates LH and FSH, these drugs actually prevent the LH and FSH surge that occurs right before ovulation. This action helps prevent the premature release of the eggs before they can be harvested for assisted reproductive technologies. GnRH agonists include leuprolide (Lupron), nafarelin (Synarel), and goserelin (Zoladex). • GnRH antagonists include ganarelix (Antagon) and cetrorelix (Cetrotide). GnRH antagonists suppress FSH and LH more than GnRH agonists, and they may require fewer injections.


Complications of Superovulation Multiple Births. Overproduction of follicles can lead to ovarian enlargement. This event increases the risk for multiple births. There is a 25% chance of multiple births (about 17% for twins and 8% for triplets and or more). Ovarian Hyperstimulation Syndrome. The most serious complication with superovulation is ovarian hyperstimulation syndrome (OHS), which is associated with the enlarged ovary (although the precise cause is unknown). This can result in dangerous fluid and electrolyte imbalances and endanger the liver and kidney. OHS is also associated with a higher risk for blood clots. In rare cases, it can be fatal. Symptoms include abdominal bloating, nausea, vomiting, and shortness of breath. Bleeding and Rupture of Ovarian Cysts. Overproduction of follicles, if unchecked, may result in bleeding and rupture of ovarian cysts. Cancer Concerns. There has been concern that clomiphene and gonadotropins may increase the risks for ovarian and breast cancer. Most evidence to date does not indicate that ovulation-stimulating drugs increase the risks for these types of cancers. However, more research needs to be done. Some studies suggest that clomiphene, which is chemically related to the breast cancer drug tamoxifen, may actually decrease the risk for breast cancer. Other Drugs Used or Under Investigation Letrozole and Aromatase Inhibitors. Aromatase inhibitors block aromatase, an enzyme that is a major source of estrogen in many major body tissues. These drugs include anastrozole (Arimidex) and letrozole (Femara). These drugs are used for treating breast cancer and are being investigated for stimulating ovulation in infertile women. Although letrozole is not approved for treatment of infertility, it has become widely used for this purpose in recent years. Progesterone. Progesterone is a hormone that is produced by the body during the menstrual cycle. Progesterone drugs are sometimes given to women who have

experienced frequent miscarriages (a possible sign of progesterone deficiency). A progesterone drug may also be given after egg retrieval during an in vitro fertilization (IVF) cycle to help thicken the uterine lining (endometrium) so it can better hold the egg following implantation. Tamoxifen. Tamoxifen (Nolvadex) is a drug known as a selective estrogen-receptor modulator (SERM). It is used to prevent breast cancer in high-risk women. It is also being studied in fertility treatments to induce ovulation. Tamoxifen works in a similar to clomiphene but may pose more health hazards, including a risk for blood clots and uterine cancer. Glucocorticoids. Glucocorticoids are steroid hormones that are sometimes used in combination with IVF and intracytoplasmic sperm injection (ICSI) to help make the lining of the uterus more responsive to egg implantation. However, recent reviews caution that glucocorticoids do not help improve pregnancy success rates and should not be used routinely with assisted reproductive technologies. Assisted Reproductive Technologies Assisted reproductive technologies (ART) are medical techniques that help couples conceive. These procedures involve either:
• •

A couples own eggs or sperm Donor eggs, sperm, or embryos

Fertilization may occur either in the laboratory or in the uterus. In the U.S., the number of live birth deliveries from ART has dramatically increased in the last decade. Nearly 40,000 live births (deliveries of one or more infants) occur in the U.S. each year using assisted reproductive technologies. Technically, the term ART refers only to fertility treatments, such as in vitro fertilization (IVF) and its variants, which handle both egg and sperm. Intrauterine Insemination (IUI)


Artificial insemination (AI) is the least complex of fertility procedures and is often tried first in uncomplicated cases of infertility. AI either involves placing the sperm directly in the cervix (called intracervical insemination) or into the uterus (called intrauterine insemination, or IUI). IUI is the standard AI procedure. IUI is less expensive and poses less risk for multiple births than the more advanced assisted reproductive technologies (ART), such as in vitro fertilization. It is useful under the following circumstances:
• • • •

When the woman's cervical mucus is unreceptive When donor sperm are required If the man's sperm count is very low When unexplained infertility exists in both partners

Those in whom IUI fails, couples with specific fertility defects, or older women may be candidates for more advanced reproductive technologies. The Artificial Insemination Procedure. The IUI procedure is as follows:
• • • •

A woman usually (but not always) takes fertility drugs in advance. The man must produce sperm at the time the woman is ovulating. The sperm are subjected to certain so-called "washing" procedures. They are then inserted into the uterine cavity through a long, thin catheter.

. The administration of fertility drugs and sperm retrieval is timed so that the process can coincide with ovulation. In Vitro Fertilization (IVF) Most assisted reproductive technologies procedures use in vitro fertilization (IVF). An in vitro procedure is one that is performed in the laboratory. Advances in these procedures have dramatically increased the rate of live births. IVF can be performed with a woman’s own eggs and sperm, or with donor eggs and sperm.

In the past, IVF was used mainly to treat women with damaged fallopian tubes. It is now used as a fertility treatment for cases when the woman has endometriosis, the man has fertility problems, or the cause of a couple’s infertility is unexplained. A standard IVF cycle is divided into the following steps: Ovarian Stimulation. Ovarian-stimulating drugs, such as clomiphene, are used to prompt the ovaries to produce multiple eggs. About 8-14 days later, another type of drug (usually human chorionic gonadotropin [hCG]) is given to foster egg maturation. • Egg Retrieval. About 34 - 36 hours after the hCG injection, the eggs are retrieved before ovulation begins. A cycle may be canceled at this stage if not enough follicles are produced or if there is a risk of ovarian hyperstimulation syndrome (see Medications section).To retrieve the eggs, the doctor inserts an ultrasound-guided probe into the vagina. A needle is then used to drain the liquid from the follicles, and several eggs are retrieved. • Fertilization and Embryo Culture. The doctor will examine the eggs to evaluate their quality and maturity. Selected eggs are placed in a culture in the laboratory and transferred to an incubator. They are then inseminated with sperm, either by placing sperm together with the egg or injecting a single sperm into the egg (see ICSI section below). • Embryo Transfer and Cryopreservation. One or more embryos are implanted in the womans uterus 1 - 6 days after egg retrieval. The doctor will discuss with the patient the appropriate number of embryos to be implanted. Excess embryos may be frozen and saved for future use. (The live birth rate is usually lower with cryopreserved embryos.) It takes about 2 weeks to determine if pregnancy has been achieved.

Other IVF Procedures. About 1 - 2% of IVF procedures use adaptations called gamete intrafallopian transfer (GIFT) and zygote intrafallopian transfer (ZIFT), which transfers the gametes (egg and sperm) into a womens fallopian tube rather than her uterus.. In GIFT, the egg is harvested as with IVF and mixed with sperm, and is then injected into the womans fallopian tube where fertilization occurs. In ZIFT, the egg is fertilized with sperm in the laboratory before being transferred to the fallopian tube. For GIFT and ZIFT a woman must have at least one functioning fallopian tube.


Success Rates. Not all IVF cycles result in pregnancy, and not all IVF-achieved pregnancies result in live births. According to the most recent statistics from the U.S. Centers for Disease Control (CDC), 34% of ART cycles (mostly IVF) led to pregnancy, but only 28% resulted in a live birth of one or more babies. Success rates provided by fertility clinics are not always a reliable indicator as they depend on many variables, including the age of the patients. Data indicate that the chances of IVF resulting in live birth are about:
• • • •

40% for women younger than age 35 30% for women ages 35 - 37 20% for women ages 38 - 40 10% for women ages 41 - 42

Some women try acupuncture during an IVF cycle to increase their chances for pregnancy success. While acupuncture is not harmful, there is no conclusive evidence that it boosts success rates. Complications. Data have been conflicting on whether IVF increases the risk for genetic abnormalities and birth defects. In general, the overall risks for birth defects appear to be small. The main risk of IVF is the consequences of multiple pregnancies. Multiple pregnancies increase the risks for a mother and her babies. In particular, there is increased risk for premature delivery and low birth weight. These factors can cause heart and lung problems and developmental disabilities in children.

Intracytoplasmic Sperm Injection (ICSI) Intracytoplasmic sperm injection (ICSI) is an assisted reproductive technology used for couples when male infertility is the main problem. It involves injecting a single sperm into an egg obtained from in vitro fertilization (IVF). The procedure is very simple:


A tiny glass tube (called a holding pipet) stabilizes the egg. • A second glass tube (called the injection pipet) is used to penetrate the egg's membrane and deposit a single sperm into the egg. • The egg is released into a drop of cultured medium. • If fertilized, the egg is allowed to develop for 1 - 2 days, then it is either frozen or implanted.

The greatest concern with this procedure has been whether it increases the risk for birth defects. Many, but not all, studies have reported no higher risks of birth defects in children born using ICSI procedures. However, if the fathers infertility was due to genetic issues, this genetic defect may be passed on to male children conceived through ICSI. Another concern has been whether the ICSI procedure is being overused. ICSI use has increased 5-fold over the past decade, even though the proportion of men receiving treatment for male infertility has remained the same. Some doctors recommend ICSI for women who have failed prior IVF attempts or who have few or poor-quality eggs, even if their male partners have normal semen measurements. According to the Society for Assisted Reproductive Technology, there is little evidence that ICSI helps improve pregnancy success for couples who do not have a problem with male factor infertility.



To do an overview of Natural micronized Progesteron, Drospirenon/Ethynil Estradiol combination &IVF market in Lucknow.


Research Methodology

• Type of Research • Type of Data • Data Collection Method
• • • •

Descriptive Primary Questionnaire Chemists/Doctors of Lucknow 110 Individual Chemist/Doctor Judgement Sampling

Universe Of Study Sample Size Sample unit Sampling Technique









NATURAL MICRONISED PROGESTERON(400MG) These are not sold in this area according to my survey.




Overview of area – 1- THAKURGANJ+CHOWK










Overview of area – 2 - DALIGANJ+IT+NIRALA NAGAR























Overview of area – 4- GOMTI NAGAR+INDIRA NAGAR


AREA-5-HAZARATGANJ+CANTT. Natural micronized progesteron(i00mg)

Natural micronized progesteron(200mg)


AREA-5- HAZARATGANJ+CANTT. Natural micronized progesteron(300mg)

Drospirenon/ethynil estradiol-




Area -6 –raniganj+ganeshganj+charbagh


Area -6- raniganj+ganeshganj+charbagh Natural micronized progesteron (200mg)


AREA-6- raniganj+ganeshganj+charbagh Natural micronized progesteron (300 mg)-

Drospirenon/ethynil estradiol-


Overview of area 6raniganj+ganeshganj+charbagh






OVERVIEW OF LUCKNOW Natural micronised progesteron(300mg)




Overview of luck now Drosperinon/ethynil estradiol


• •

This market is flooded by a number of players . Though there are many players in the market of Natural micronised progesteron in each strength ,but the clear cut market leader in this field is SUN pharmaceuticals(with its product SUSTEN). It is found that 100 and 200 mg are the frequently prescribed strengths in Natural Micronised Progesteron market. High strength is being prescribed by very few doctors. The high end combined oral contraceptives pills (DRSP/EE) are available to some selected retail outlets. The Drospirenon/Ethynil Estradiol market are being shared by the some of the topmost pharmaceuticals companies, but the dominating players are GERMAN REMEDIES (YASMIN) and LUPIN (YAMINI). It is observed during the project that infertility cases are on rise and there is an increasing trend for infertility treatment.

• It is found that these patients are being treated by specialist doctors having expertise in IVF/IUI. • Medicines used for IVF/IUI are being dispensed by the doctors themselves instead of prescribing from retail chemists. This mar is influenced by multiple factors like quality and batch to batch consistency ,cold chain maintenance, doctor’s obligations and special rates to the hospitals .It’s a huge undercover market having national and multinational players.

From the analysis ,we can concluded that –






• Gynecology market is a huge one with no clear cut leader in the market hence it is an opportunity for the pharmaceutical companies to grab the maximum business.

• Retail Availability.

Maximize ROI (Return on Investment)-Proper feedback of retailer is utmost important to maximize the return on investment of a company.

Regular meeting with the retailers.

• Interpersonal relationship with the retailers.

Bonus offers or personal benefits to the retailers.

As far as IVF and IUI market is concerned it is very important to have a strong customer knowledge which includes his prescription habits , area of interests ,profile etc.


• Another important aspect of this segment is to keep a strong vigil on product movement, timely order procurement, efficient & timely supply under strict quality control.



1. As the universe size is too large. So I have conducted my survey in a limited area.

Few of respondents did not want to give their sales informations like they said that how they can give their sales records. Few respondents said that “we don’t want to participate in any survey; we don’t have time for such types of things”.


4. It is not possible to have 100% accurate data from the respondents.


1. Jindal SK, Gupta D, Aggarwal AN, Study of the prevalence of GYNEACOLOGY. Volume 37 2. Worldwide variations in the prevalence of VAGINAL, Lancet 1998. 3. Turato G, Zuin R, Saetta M. Pathogenesis and pathology of. ABORTIFICANT 2001 5. Ratageri VH, Kabra SK, Dwivedi SN, Factors associated with severe PREGNANCY . Indian Pediatr 2000. 6. Lupin’s Strategy Guide, April – June 2008. 7. The Statesman, New Delhi Monday 11 July 2007. 8. 9. 10. 11. Indian Journal Medical Research, November 2008.