Pioneer Batch  Class of 2012

MODULE LECTURE

Gynecology Drugs for Reproductive Endocrinology

DATE LECTURER

22 October 2009 Ma. Stephani Fay S. Cagayan MD, FPOGS

OUTLINE I. Introduction II. Physiology of reproductive hormones A. Reproductive hormones B. Gonadal hormone synthesis C. Steroid hormone and its receptor D. What regulates the synthesis of sex hormones? E. Prerequisites of normal menstration III. Female gonadal hormones A. Estrogen B. Progesterone C. Oral contraception D. Estrogen and progesterone Inhibitors and antagonists IV. Male gonadal hormones A. Androgens and anabolic steroids B. Anti-androgens V. Other hormones A. GnRH B. FSH VI. Summary (must-read)

A. Reproductive hormones - Sex hormones = gonadal hormones o Estrogens o Progestins o Androgens - Gonadotropins o LH o FSH - GnRH B. Gonadal hormone synthesis - Steroid hormones are derived from cholesterol - Normal human ovary produces all three classes of SEX STEROIDS divided into main groups according to the number of carbon atoms they possess:  21 carbon series – PROGESTINS (pregnane nucleus)  19 carbon series - ANDROGENS (androstane nucleus)  18 carbon series - ESTROGENS (estrane nucleus) C. Steroid hormone and its receptor

Transcriber’s note: Dr. Cagayan had some “hidden slides” (around 20, and in blue) in the Powerpoint file, but the group decided to include it all in the trans, hence the length… I. INTRODUCTION General objective To acquire an understanding of the action of the different sex hormones and other hormones utilized in the pharmacology of reproductive endocrinology Specific objectives - To be able to review the physiology of normal menstrual cycle - To list the different sex hormones, know their biosynthesis (chemical compositions), mechanism of action, pharmacokinetic properties, physiologic and metabolic effects - To describe clinical/therapeutic applications of these hormones - To list side effects and/or adverse reactions to these drugs Different hormones in reproductive endocrinology - Biosynthesis (chemical compositions) - Mechanism of action - Pharmacokinetic properties - Physiologic and metabolic effects - Clinical and therapeutic application - Adverse effects II. PHYSIOLOGY OF REPRODUCTIVE HORMONES Page 1 of 13

- Do you still recall you receptors? o Ion channel receptors o G Protein coupled receptors o Tyrosine kinase receptors o Intranuclear receptors – where sex hormones react with - Although separate P, A and E receptors exist, complete selectivity of action does NOT exist because of the close structural similarities of the hormones - For example, most progestins have significant cross reactivity with androgen receptors, and prolonged progestin administration produces an androgenic effect (virilization or the

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Hypothalamic-pituitary-reproductive axis . and withdrawal bleeding occurs III. and so on… E.7 First you have your menses from Day 1 to 5 o Shedding of the endometrium Day 1 – 14 – follicular phase – predominantly estrogen Day 15 – 28 – luteal phase – predominantly progesterone Midpoint is usually day 14 – LH surge – when ovulation occurs o So egg is released. What regulates the synthesis of sex hormones? . Estrogens 1.“It’s common among law and medical students to have irregular menses…” Female Theca Androstenedio ne synthesis - Video of the menstrual cycle Ano palagi ang point of reference ? – day 1 of menses What’s regular menses? 28 days +/.Most synthetic progestins have been modified to minimize their androgenic side effects D.Pioneer Batch  Class of 2012 MODULE LECTURE Gynecology Drugs for Reproductive Endocrinology DATE LECTURER 22 October 2009 Ma.FEMALE GONADAL HORMONES A. Cagayan MD. nagkakaroon ng hirsutism…) . Prerequisites of normal menstruation - Hypothalamic-pituitary-reproductive axis: TWO CELL-SYSTEMS o Males o Females An intact HPO axis Estrogen-induced proliferative endometrium Ovulation at midcycle progesterone-induced secretory endometrium if pregnancy does not occur. if it sees a sperm. the hormones decline. it gets fertilized. and then caught by the fallopian tube.Major natural estrogens in human: o Estradiol – most abundant Male LH Leydig Testosterone synthesis FSH Sertoli Increases production of Page 2 of 13 Bestfriends4ever . FPOGS ABP Spermatogene sis Granulosa Increases aromatase activity development of masculine features – bumababa yung boses. Biosynthesis (chemical compositions) . Stephani Fay S.

ang pinaka-goal ng tao ay to perpetuate the species .The synthetic progestins .Synthesized in the ovary.The most important progestin in human .Responsible for the increased clotting factors and increased renin substrate 4.Estrone (E1) and estriol (E3) .Required for sexual maturation of the female .Hormonal contraception . but more prone to cancers due to prolonged estrogen stimulation Estriol . breast tenderness B.Serves as a precursor to the estrogens. X – take note because one of the major side effects of these meds is thrombosis Induce the synthesis of progesterone receptors Taking estrogenic pills just extends the physiologic effect of the hormone - - 5.E2 (liver) .Uterine bleeding .Primary hypogonadism . Physiologic and metabolic effects . renin substrate Increase the levels of Factors II. IX.Hydroxylated derivatives and conjugated metabolites .Endometrial cancer . large amounts are also synthesized and released by the placenta during pregnancy . Mechanism of action . TBG.Post-menopausal hormonal therapy 6.Block resorption of bone Page 3 of 13 Bestfriends4ever . Pharmacokinetic properties . LOWER affinity to albumin .The natural progestins: Progesterone . testis and adrenal from circulating cholesterol. Progesterone 1.Promote endometrial proliferation during follicular phase – Prepares uterus for implantation of the blastocyst – kasi in the end.Other effects: nausea. Cagayan MD.Some synthetic estrogens Ethinyl estradiol • The addition of the ethinyl group has altered the bioavailability of estrodiol (possible to be taken orally) Estradiol cyponate Estrone sulfate Mestranol Estradiol valerate Equilin sulfate DATE LECTURER - 22 October 2009 Ma.Orally administered estrogens have HIGH ratio of hepatic to peripheral effects .21 carbon compounds .Estradiol (E2) binds STRONGLY to αglobulin (SHBG).Estrogen receptor - Actions mediated by ESTROGEN RECEPTORS (alpha and beta) which are ligand-regulated transcription factors 3. Biosynthesis (chemical compositions) . FPOGS Increase the levels of HDL and triglycerides and decrease the levels of LDL and total cholesterol Increase SHBG. Adverse effects .Most closely related to progesterone • Hydroxyprogesterone acetate • Medroxyprogesterone acetate • Megestrol • Dimethisterone 2. VII.Pioneer Batch  Class of 2012 MODULE LECTURE Gynecology Drugs for Reproductive Endocrinology o Estrone – most abundant during menopause  From peripheral conversion of androstendione by fat  That’s why chubby menopausal women are somehow protected from osteoporosis. androgens and adrenocortical steroids . Stephani Fay S. Clinical and therapeutic application .

Dizziness .Metabolism of ethinyl estradiol (EE) VARIES SIGNIFICANTLY from individual to individual.Promote endometrial development during luteal phase .Has depressant and hypnotic effects on the brain . FPOGS by estrogens → → (+) withdrawal bleeding Applicable for women with amenorrhea - 2.Removal of 19-carbon from ethisterone formed NORETHINDRONE → changed major hormonal effect from an androgen to progestational agent → 19 nortestosterone . Physiologic and metabolic effects .Therapeutic application o Hormonal contrapcetion o Hormonal replacement therapy o Endometriosis .So if your patient asks you. Combination oral contraceptives (COCs) a.In the liver.Has little effect on protein metabolism .Pioneer Batch  Class of 2012 MODULE LECTURE - Gynecology Drugs for Reproductive Endocrinology 19-nor. don’t you have any pill would not cause hirsutism. “Doktora.DOSE OF ESTROGEN – a critical issue in selecting an oral contraceptive .Headache .Almost completely metabolized in one passage through the liver . and from one population to another .Decreases amount of cervical mucus and increases its viscosity .E2 + ethinyl group at the 17 position = Ethinyl Estradiol --orally active .ESTROGEN CONTENT of the pill is of major clinical importance ---THROMBOSIS is dose-related . Pharmacokinetic properties .Weight gain . Clinical and therapeutic application .E2 is the most potent natural estrogen --.Testosterone  ethisterone  norethinedrone Bestfriends4ever 3.Antagonize actions of aldosterone – recall effect of aldosterone – salt and water retention .Diagnostic application .A test of estrogen secretion: Progesterone challenge test .Reversible reduction of glucose tolerance C. Mechanism of action Actions mediated by progesterone receptors (A and B isoforms) which are ligand-activated transcription factors 6.Has more marked effect on carbohydrate metabolism: progesterone increases basal insulin levels and the insulin response to glucose .Bloating . 13 ethyl compounds claimed to have lower androgenic activity than older synthetic progestins • Desogestrel • Gestodene • Norgestimate DATE LECTURER 22 October 2009 Ma. Stephani Fay S. Progestin only pills (POPs) 1. Cagayan MD.MPA 10mg/d for 5 days – when endometrium has been stimulated Page 4 of 13 .Half-life is 5minutes .Its effects on the uterus are essential for maintenance of pregnancy 5.It is excreted into the urine as pregnanediol glucuronide 4.Rapidly absorbed following administration by any route . Combination of progestins and estrogens – Combination oral contraceptives (COCs) 2.So you would want an estrogen dose that is low b.Stimulate growth and development of breasts during pregnancy .inactive orally . COCs progestin component: pharmacology 2 major types of synthetic progestins o Derivatives of 19 nortestosterone o Derivatives of 17-α acetoxyprogesterone . Adverse effects . it is metabolized to pregnanediol and conjugated with glucuronic acid .all progestational agents have some degree of androgenic activity . Oral contraception Hormonal contraception in women 1. etc…” sad to say… wala! .Increases basal body temperature – pero transient lang ‘yan… alam niyo ‘yung feeling ng “in heat” .Increases body temperature . COCs estrogen component: pharmacology .Increases ventilatory response to CO2 .

Reduces sperm transport in the upper genital tract (fallopian tubes) . Stephani Fay S. making implantation less likely .Gonanes • Levonorgestrel • Norgestimate . and it has low androgenic effect .Thickens cervical mucus (preventing sperm penetration f.Norethindrone .Most are converted to the parent compound. norgestimate are derivatives of levonorgestrel Reduced androgenicity (increased sex hormone binding globulin.Norethynodrel .Typical use failure rate: 7. 6/5/10) e.Administered with interruption (21 days on. norethindrone .Biphasic: 21 active pills contain 2 different E/P combinations (e.1% .Marketed for noncontraceptive usage .2nd generation COCs – products with levonorgestrel.Strict adherence to 7-pill free days is critical to obtain contraception - - - - - Page 5 of 13 Bestfriends4ever . and other members of the norethindrone family and <50ug EE .Perfect use failure rate: 0.Norethindrone acetate .Pioneer Batch  Class of 2012 MODULE LECTURE - Gynecology Drugs for Reproductive Endocrinology 19-nortestosterone .Ethynodiol diacetate .Triphasic: 21 active pills contain 3 different E/P combinations (e.g. gestodene.g. 7 days off) .Lynestrenol .6% .Usually containing ethinyl estradiol and norethindrone . Mechanism of action .Pregnancies usually occur because initiation of the next cycle is delayed .1st generation COCs – products with > 50ug of EE .Norgestrel Other progestins o Levonorgestrel is the active isomer of norgestrel New progestins o Desogestrel. so you just give it for compliance. Cagayan MD.3rd generation COCs – products with desogestrel or gestodene and <50ug of EE d.Monophasic: All 21 active pills contain same amount of Estrogen/Progestin (E/P) .Medroxyprogesteron acetate and megestrol acetate . the last 7 tablets are just ferrous sulphate because these are the days when the girl is suppose to menstruate. Usually in the 28-day preparations.Changes endometrium.with greater progestational activity • Desogestrel -with greater progestational activity Norethindrone family .. Types of COCs . FPOGS “Current formulations of COCs are made from SYNTHETIC steroids and contain no natural estrogens or progestins. you would want it to have a low estrogen component and a progesterone component with high progestational activity and low androgenic activity – you just the minimum effective dose Drospirenone – analogue of spironolactone. 10/11) (ma’am thinks it’s the progestin dose that changes) . has affinity for mineralcorticoid receptor and antimineralcorticoid effect (Yasmin) – prevents bloating due to the antimineralocorticoid effect. .Progestin suppresses LH secretion while estrogen suppresses FSH secretion  suppresses ovulation . and it’s cheap! 17 α acetoxyprogesterone .How do you administer these? Usually there are 28-day pills and 21-days.PREGNANES .with greater progestational activity • Gestodene . but ma’am says that the Trust pills also have the same effects.Estranes • Norethindrone • Norethynodrel • Norethindrone acetate • Ethynodiol acetate ..C21 progestins .Injectable depomedroxyprogesterone acetate DATE LECTURER 22 October 2009 Ma. norgestimate. Efficacy .Structurally related to progesterone .” c. decreased free testosterone) If you formulate a new type of OCP. Low-dose oral contraceptives – products with <50ug of EE .

g. FPOGS or have cardiovascular risk factors  No increase in mortality due to MI or stroke in healthy.Thrombosis .It can be stated definitely that oral contraceptive use DOES NOT produce an increase in diabetes mellitus. IX. Carbohydrate metabolism . you follow-up.Glucose intolerance is doserelated – when you stop taking OCP.Insulin sensitivity is affected mainly by the PROGESTIN component of the pill . an evaluation to search for an underlying abnormality in the coagulation system is warranted . essentially limited to localized and a vey small increase in the number of actual cases .Insulin and glucose changes with low dose monophasic and multiphasic OCs are so minimal and clinically insignificant . Metabolic effects .Venous thromboembolism  Deep vein thrombosis (DVT)  Pulmonary embolism o Arterial thrombosis  Myocardial infarction  Stroke . have an increased risk of VTE.Past users of oral contraceptives DO NOT have an increases incidence of cardiovascular disease . Stephani Fay S.But this might not be related entirely to OCP use.Current and recent (1-4years) use of OCs may be associated with 20% increased risk of early (<35) premenopausal breast cancer.NO EFFECT of past use or duration of OC use (up to 15 years of continuous use) . regardless of progestin type. X) . non-smoking women.LOW DOSE oral contraceptives are VERY SAFE for healthy young women. VII.May be due to:  Detection/ surveillance bias  Accelerated growth of already present malignancies . babalik sa dati . regardless of age Almost all MI and strokes in OC users occur in users of HIGH dose products or users WITH CARDIOVASCULAR RISK FACTORS Cardiac deaths occurred in only in women who smoked >15 cigarettes per day New studies emphasize the importance of good patient screening  Arterial thrombosis is limited to older women who smoke - - Page 6 of 13 Bestfriends4ever .NO INCREASED RISK on use of high dose OCs .Hypertension is a very important additive risk factor for stroke in OC users All low dose OCs.Pioneer Batch  Class of 2012 MODULE LECTURE - Gynecology Drugs for Reproductive Endocrinology If with vomiting & diarrhea → back-up method for 7days or put pill in the vagina DATE LECTURER 22 October 2009 Ma.Previous use may be associated with a REDUCED RISK of metastatic cancer LATER in life.Older high dose OCs – (+) impaired glucose tolerance . non-smoking women . and get checked .If a patient has a family history of idiopathic thromboembolism. they say na tumataas daw yung discovery kasi when you use OCP.Progestins have no significant impact on clotting factors . Cagayan MD.Pharmacologic estrogen increases the production of clottign factors (II. concentrated in the 1st 2 years of use Recent studies reinforce the belief that the risks of arterial and venous thrombosis are a consequence of the ESTROGEN component of COCs Smoking has a lesser effect on the risk of venous thrombosis compared with arterial thrombosis Smoking and estrogen have an additive effect on the risk of arterial thrombosis Low dose OCs DO NOT increase the risk of MI or stroke in healthy. Risk of breast cancer .Thrombosis: 2 major categories .

Non-contraceptive benefits .Benefits to treat and manage problem and disorders o Dysmennorhea o Endometriosis o Replacement therapy in ovarian dysfunction o Dysfunctional uterine bleeding (DUB) o Postmenopausal symptom j.FEAR OF SIDE EFFECTS: most common reason why patients discontinue oral contraception . test them first .Pioneer Batch  Class of 2012 MODULE LECTURE Gynecology Drugs for Reproductive Endocrinology and REDUCED RISK of postmenopausal breast cancer NO INCREASED RISK in women with positive family history for breast cancer/women with benign breast disease DATE LECTURER 22 October 2009 Ma. coronary occlusion or past history of these conditions – if there’s family history. Absolute contraindications . Stephani Fay S.COCs are safer than most people think.Pelvic examination not required to initiate use – just make sure she’s not pregnant. thromboembolic disorders.Can be provided by trained nonmedical staff i.Can be prescribed without a clinical breast and pelvic examination .Thrombophlebitis.Incidental benefits o LESS ENDOMETRIAL CANCER o Use for 12 months reduces the risk by 50%. treatment is initiated at the first 5 days of menses. FPOGS Known or suspected breast cancer Markedly impaired liver function – because your OCPs are metabolized hepatically Undiagnosed abnormal vaginal bleeding Known or suspected pregnancy - h. UNLESS irregular yung mens .Do not interfere with intercourse .Untreated hypertension – if hypertension is treated. Greatest protective effect if use for >3 years o LESS OVARIAN CANCER: Risk is reduced by 40% (3 years) to 80% (>10 years of use) o Fewer ectopic pregnancies o More regular menses – less flow.Client can stop use . at least once o Women >35 y/o o Women with strong family history of heart disease. anemia o Less salpingitis o Increased bone density o Possibly less benign breast disease o Possibly fewer ovarian cysts . Clinical decisions: surveillance . pwede pa rin . Usually.Smokers over the age of 35 Page 7 of 13 k.Few side effects .Utilize the formulations that give effective contraception and the greatest margin of safety. DM.Most important use is for ORAL CONTRACEPTION . lipids and lipoproteins: o Young women. ‘pag may regla sure ka na ‘di buntis.Reassess new users within 1 to 2 months . cerebrovascular disease.Patients need be seen only every 12months .Severe hypercholesterolemia or hypertriglyceridemia . Bestfriends4ever . Cagayan MD. Relative contraindications Systemic lupus erythematosus Sickle cell disease Gestational diabetes mellitus Diabetes mellitus Hyperlipidemia Controlled hypertension Smoking Migraine headaches Seizure disorder Hepatic disease Obstructive jaundice in pregnancy Gallbladder disease Mitral valve prolapse Uterine leiomyomas Elective surgery l.Convenient and easy to use . Contraceptive benefits .The therapeutic principle remains: . dysmenorrhea. .Laboratory surveillance should be used only when indicated .Perform yearly breast and pelvic examination on follow up .The ff patients should be monitored with blood screening tests for glucose.HPN o Women with GDM o Obese women o Diabetic women m. COCs: choice of pill .

the estrogen content is not sufficient to stimulate endometrial growth o Progestational effect dominates to such a degree that a shallow atrophic endometrium is produced. Drugs that affect efficacy of COCs .OCs alter clearance rates of Paracetamol and ASA .Thickens cervical mucus . start a new cycle o If BB is prolonged or is aggravating to the patient – (For 7 days): take conjugated estrogen 1.Contains a small dose of a progestational agent Page 8 of 13 Bestfriends4ever . lacking sufficient tissue to yield withdrawal bleeding → AMENORRHEA o There is no harmful permanent consequence of amenorrhea while on OC o ANXIETY in both patient and clinician -. Tricyclic antidepressants. Progestin-only pills (POPs) .a Mechanisms of action .Changes endometrium.Pioneer Batch  Class of 2012 MODULE LECTURE - Gynecology Drugs for Reproductive Endocrinology Current data support that there is GREATER safety with low dose preparations There is LITTLE difference between the low dose monophasics and the multiphasics DATE LECTURER 22 October 2009 Ma. no matter what oral contraceptive formulation is used.Pwede sa mga embolic patients .Suppresses ovulation (but not consistently) . even the lowest dose products.OCs potentiate the action of Diazepam. Theophylline .Breakthrough bleeding (BB) o Irregular bleeding in the first few months after starting oral contraception o Unexpected bleeding after many months of use o There is NO evidence that the onset of bleeding is associated with decreased efficacy.Bakit di pwede sa lactating mothers? Because estrogen will suppress breastmilk production .Alternative to lactating mothers – para di mabuntis kaagad. FPOGS o Taking of 2-3 pills is NOT effective o The PROGESTIN component will always dominate – doubling the pills → double the progestational impact → double the decidualizing and atrophic effect on the endometrium and destabilizing effect on endometrial blood vessels o ADD ESTROGEN ( do not add progestin) Amenorrhea o With low dose pills. Stephani Fay S. Clinical problems .Reduces sperm transport in upper genital tract (fallopian tubes) . .LARGER doses may be required in OC users 3. making implantation less likely .major problem Weight gain Acne Ovarian cysts n. Chlordiazepoxide . Cagayan MD. wait 7 days. o Most frequently encountered occurs in the first few months of use o Higher in women who smoke o Best managed by ENCOURAGEMENT & REASSURANCE o Disappears by the 3rd cycle o Represents tissue breakdown as the endometrium adjusts from its usual thick state to the relatively thin state allowed by hormones in OC o BB after many months of use is a consequence of progestininduced decidualization o Endometrium and blood vessels within the endometrium tend to be fragile and prone to breakdwon and asynchronous bleeding o 2 factors associated with BB:  Inconsistency of pill taking – more important and has a greater effect in later cycles  Smoking – exerts a general effect at any time o REINFORCEMENT OF CONSISTENT PILL-TAKING can help minimize BB o If bleeding occurs before the end of the cycle: stop the pills.LOWER doses of the above agents in OC users .25mg and estradiol 2mg - - o.

breast tenderness. Stephani Fay S.Client can stop use .Can be provided by trained nonmedical staff . headache.May improve anemia .Few side effects .d Non-contraceptive benefits .Do not interfere with intercourse .These are high-dose preparations.05–5 pregnancies per 100 women during the first year of use) .Irregular menstrual bleeding – major reason why women discontinue POPs .b Efficacy . abdominal and leg cramps .Types o Estrogen (ethinyl estradiol) + progestin (norgestrel).May decrease menstrual cramps .Pioneer Batch  Class of 2012 MODULE LECTURE - Gynecology Drugs for Reproductive Endocrinology Must be taken daily in a continuous fashion Must be taken every day of the SAME TIME Change in cervical mucus o Requires 2-4hours to take effect o Impermeability diminishes 22 hours after administration o By 24hours sperm penetration is essentially unimpaired DATE LECTURER 22 October 2009 Ma.g Clinical decisions .Pelvic examination not required prior to use .High doses (like 3 or 4 tablets at one time) but for a few days .More functional ovarian cysts .Morning-after pill . Cagayan MD. impair ovum transport .Levonorgestrel associated with acne .2 situations in which excellent efficacy is achieved: o Lactating women  No evidence of any adverse effect on breastfeeding  Women breastfeed longer and add supplementary feeding at a later time  Can be started IMMEDIATELY after delivery o Women age over 40 3. FPOGS Missed pills – take missed pill ASAP.5mg BID for 5 days 600mg once (with Misoprostol 400 ucg once) 0.75mg BID for 1 L-Norgestrel Page 9 of 13 Bestfriends4ever .Decrease ectopic pregnancy . suppress the hypothalamicpituitary.e Problems .Decrease benign breast disease .Effectiveness: 90-98% if taken within 72 hours of unprotected intercourse .Pill intake should be keyed to a daily event to ensure regular administration at the same time of the day .Schedules for use Conjugated 10mg TID for 5 Estrogens days Ethinyl Estradiol Mifepristone 2.f Pill-taking . promotes menstrual bleeding o If fertilization has not occurred: decrease the amount and increase the viscosity of cervical mucus.Convenient and easy-to-use .gonadal axis.Adverse effects o Nausea and vomiting. Postcoital contraception .Do not affect breastfeeding .Mechanism of action o If fertilization has occurred: prevents implantation.Protect against endometrial cancer .Back-up method must be used for the 1st seven days because some women may ovulate as early as 79 days after menses .Protect against some causes of PID .Is it an abortifacient? Ethical question… . back-up method should be used until resumed for at least 2 days If more than 3hrs late – back-up method for 2 days - . o Estrogen alone o Progestin alone .Minipill should be started on the first day of menses . dizziness.c Contraceptive benefits . when you think that you did it at the wrong time .Immediate return of fertility when stopped .May decrease menstrual bleeding .Contain no estrogen .Effective when taken at the same time every day (0.

resulting in only a partial disruption of gene expression and cell growth .5 mg 0. induce bleeding first before regulating.Competitive partial agonist inhibitor of estradiol at the estrogen receptor .Synthesis inhibitors Aromatase inhibitors o Letrozole o Anastrozole .Pioneer Batch  Class of 2012 MODULE LECTURE Gynecology Drugs for Reproductive Endocrinology day Norgestrel EE 0. then regulate If a patient is oligomenorrheic. don’t give OCP. Inhibitors of estrogen . stop the bleeding first.Tamoxifen o Extensively used in the palliative treatment of breast cancer in postmenopausal women o Approved for chemoprevention of breast cancer in high risk patients o Prevent he expected loss of lumbar spine bone density and plasma lipid changes consistent with a reduction in the risk of atherosclerosis o Agonist activity also affects the uterus.05 mg 2 tab and 2 tabs in 12 hours DATE LECTURER 22 October 2009 Ma. but block the activation of cofactors in the nucleus. o It is approved for the prevention of postmenopausal osteoporosis – but now orthos refer bisphosphonates Clomiphene citrate o Stimulates ovulation in oligomenorrhea or anovulation o Good for PCOS o Acts as an estrogen receptor antagonist in the hypothalamus and pituitary gland and as a partial agonist in the ovaries o Antagonistic activity – results in relief of the negative feedback inhibition imposed by the endogenous estrogen – increased release of GnRH and gonadotropins . Cagayan MD. Estrogen and progesterone inhibitors and antagonists 1. and may increase the risk of endometrial cancer . FPOGS o Partial agonist-antagonist at some but not all target tissues o It has similar effects on lipids and bone but appears not to stimulate the endometrium or breast ( an attractive drug for the prevention of breast cancer) o Raloxifene is good in menopausal women with intact uterus because it’s antagonistic to the uterus so you avoid risk of - - If you use your OCP to regulate your follicle.a Receptor antagonists: SERMs . just stop the bleeding and give ovulationincduction agents If a patient is heavily menstruating. Stephani Fay S. gusto niya maging regular pero gusto rin mabuntis. used in HRT to prevent osteoporosis o Clomiphene – ovulation-induction agents . Inhibitors of the synthesis of estrogens Bestfriends4ever Page 10 of 13 .Raloxifene - endometrial cancer.b Selective estrogen receptor modulators (SERMs) and estrogen receptor antagonists Bone Brea CV Uteru st Syste s m Estradiol Ag Ag Ag Ag Clomiphe ne Tamoxife nn Raloxifen e Anta g Ag Ag Anta g Anta g Anta g Antag Antag Ag Anta g Anta g Anta g 2.Allow the receptors to dimerize. di ka mabubuntis If a px comes to you of irregular menses.Receptor antagonists Selective estrogen receptor modulators (SERMs) o Tamoxifen – for breast cancer o Raloxifene – your designer estrogen. D.

2% remains free and available to enter cells and bind to intracellular receptors .65% of circulating T is bound to SHBG .T → DHT (skin.Inhibits progesterone action by binding competitively to the progesterone receptor . prostate. epididymis) .alkylated androgens are effective when given orally but has more side effects.Pioneer Batch  Class of 2012 MODULE LECTURE Gynecology Drugs for Reproductive Endocrinology DATE LECTURER 22 October 2009 Ma. seminal vesicles. letrozole 3.Acts intracellularly . blocking the aromatase enzyme can effectively inhibit estrogen formation .It can be used to inhibit the growth of estrogen dependent tumors. for example. FPOGS Aromatase inhibitors .Long acting GnRH agonists (or antagonists) to inhibit pituitary function followed by FSH to stimulate follicular growth and hCG to stimulate ovulation Progesterone receptor antagonists .RU 486 (mifepristone) .All actions are mediated by the androgen receptor which is a ligand activated transcription factor .Not available in the country because it’s considered an abortifacient - Mechanism of action . differentiation. Cagayan MD.Follicle stimulating hormone .Conversion of T to E2 by P450 aromatase Hypothalamic-pituitary-testicular axis Biosynthesis (chemical compositions) - Page 11 of 13 Bestfriends4ever .95% produced by the Leydig cells. Stephani Fay S.Testosterone – most important androgen secreted by the testis .MALE GONADAL HORMONES .T is converted to DHT by 5α reductase . synthesis of proteins Pharmacokinetic properties Ineffective when given orally but can be administered transdermally or parenterally Testosterone esters can be given intramuscularly 17 α. especially hepatic toxicity Physiologic and metabolic effects of androgens - IV.T and DHT bind to intracellular androgen receptor → growth.Human chorionic gonadotropin .A Androgens and anabolic steroids .Anastrozole.May be used as an ovulation inducing agent .Aromatase inhibitors . Ovulation-inducing agents .Because estrogens are synthesized from androgen precursors via the action of AROMATASE. 5% by the adrenal gland .Clomiphene citrate . breast cancer .

Pioneer Batch  Class of 2012 MODULE LECTURE Gynecology Drugs for Reproductive Endocrinology DATE LECTURER 22 October 2009 Ma. Cagayan MD. The frequency of GnRH pulses controls the relative release of LH and FSH by the anterior pituitary gland. biclutamide. for hirsutism V.Spironolactone – aldosterone antagonist. Most important SE in progestin? o Carbohydrate metabolism effects. combination OCPs.Clomiphene followed by FSH to stimulate follicular growth and hCG to stimulate ovulation VI. Finasteride . FSH .Ovarian follicle maturation can be enhanced by treatment with FSH . pituitary gonadotroph activity B.These high levels of FSH can be further augmented by using the recombinant form of the protein leading to maturation of an increased number of follicles . LH. IX.Flutamide.Increased levels of FSH are normally produced by the anterior pituitary gland prior to and just after ovulation .Virilization (in females. hepatic carcinoma What are the different hormones that we discussed? o Estrogen. Stephani Fay S. androgenic effects in OCP are also good due to effect in libido Increase lean body mass Decrease SHBG.Selective inhibitor of type II 5 α reductase . Androgen receptor antagonists . hirsutism.Blocking the local conversion of T to DHT effectively stops the action of T . FPOGS - - - General growth promoting properties of androgens on body tissues Responsible for penile and scrotal growth and changes in the skin ( appearance of pubic. Testosterone What are the receptors of sex hormones? o Intranuclear receptors The most important application of these drugs would be for…? o Contraception Main mechanism of contraceptives? o Inhibits ovulation Most important SE of estrogen agonists? o Thrombosis because of increase in clotting factors II.The hypothalamus releases GnRH in a PULSATILE fashion. jaundice.SE: Erectile dysfunction Page 12 of 13 . FSH. Progesterone. VII. and X. HDL.Edema. CAH and male precocious puberty .CONTINUOUS administration of GnRH suppresses.Cyproterone acetate – for hirsutism . Increase LDL 2. prepubertal boys) .Effective treatment for BPH . GnrH. rather than stimulates. glucose intolerance What are your strogen inhibitors? o Aromatase inhibitors and estrogen receptor antagonist What are your progesterone inhibitors? o Mifepristone Testosterone is your active ligand in what organ? Bestfriends4ever - . their antagonists. . nilutamide: o Treatment of prostate cancer. axillary and beard hair) Stimulate skeletal growth and epiphyseal closure Play an important role in stimulating and maintaining sexual function in men – that’s why in women.B Anti-androgens 1.Main use as replacement therapy in male hypogonadism Adverse effects .Suppression of HPG axis . SUMMARY (highly recommended that you read this part) Clinical and therapeutic application of androgen therapy . OTHER HORMONES A.Feminization (males) . GnRH .

there was a distinct extra voice singing with them. the one being operated on. She stood up. This happened to our friend who was in Canada then. He was chatting with his fiancee via the webcam when she asked him who was the lady who was with him in his room. Once our choir was recording our song for a cd project.Pioneer Batch  Class of 2012 MODULE LECTURE Gynecology Drugs for Reproductive Endocrinology DATE LECTURER 22 October 2009 Ma. Stephani Fay S. led us to the room and opened the door. When they played back the track. my nephew (brother’s son) would always be awakened at night. it’s always 3am. Anak: “Tay. I’d open it. all the members of our team woke up gasping for air. “What playmate?” His kid told him. hormonal imbalance. adenomyosis. 9. wala tayong yaya!” Me and my officemates had a sleepover. One time our kasambahay told me she sees a white lady in my room. 7. 8. time and again I’d be awakened by 3 loud knocks on my bedroom door. 3. Langya ka. Two years ago my dad was deathly sick. “can you watch over my playmate?” He freaked out and 2. And they say when this child appears.” 10. “pagagalingin ko lolo mo. totoo po bang may multo?” Tatay: “Anak walang multo! Bakit mo natanong?” Anak: “Sabi kasi ni yaya may multo raw!” Tatay: “Anak. 5. so he ran out of his house. FPOGS - - o The muscle How about in your seminal vesicle? o DHT T  DHT through what enzyme? o 5α reductase Inhibited by what drug? o Finasteride Used in? o BPH Adverse effect? o Erectile dysfunction Clomiphene citrate is used for…? o Ovulation induction You can also give what with clomiphene? o FSH (and β-hcg. by a small black creature saying. One night. will die. She said her daughter died there with her eyes open. And when I check the clock. and in the middle of the night. “sabunutan ko pa yun eh!” The next morning. When it was the sopranos’ turn. they went into the small booth and sang into mike. all red. I woke up with scratches on my face. He freaked out because he was alone. AUB. pero sasama ka sa akin…“ My sister is a nurse at a popular hospital. Cagayan MD. The next morning he couldn’t resist so he asked the owner why the “secret” room was red. In a boarding house in Calumpit. Page 13 of 13 Bestfriends4ever . When our friend was peeking in. In our old house. her daughter was probably peeking out at the same time. We all had the same dream: that someone was suffocating us with our pillow. 6. My friend’s 4-year-old son was playing in his room when the kid told him. During that time. Something for Halloween: The Top Ten Signs That Your House Is Haunted 1. replacement therapy for hypogonadism… Make sure your patient is not pregnant before giving your therapy! THE END! asked. mag-impake ka na. “that black kid beside you. All he saw was red. but was not discussed) Other use for your pills? o Dysmenorrhea. around 3-4am. our friend got too curious and peeked inside the keyhole. It was all white. and no one would be there. She heard stories about a child that appears at a certain operating room. the owner warned us not to mess around with the room at the end of the corridor. 4. myoma. endometriosis. I joked.

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