Dr.

Alis Uworld Notes For Step 2 CK

Gyn
Menstruation Cycle & Cervical Mucus Consistency

The early follicular phase immediately follows menstruation. The cervical mucus in this phase is
THICK, scant and acidic. It does not allow penetration by spermatozoa.

In the ovulatory phase, cervical mucus is profuse, clear and THIN in contrast to the mucus of
the post- and pre-ovulatory phases, which is scant, opaque and thick. Evaluation of the cervical
mucus is part of the infertility workup as "hostile" cervical mucus can disallow penetration of
spermatozoa into the uterus. Normally, cervical mucus in the ovulatory phase stretches to
approximately 6 cm when lifted vertically (spinnbarkeit), its pH is 6.5 or greater (more basic
than at other phases), and will demonstrate "ferning" when smeared on a microscope slide.

In the mid- and late-luteal phase, ovulation has already occurred, in these phases. The cervical
mucus becomes progressively THICKER and exhibits less stretching ability. This mucus is also
inhospitable to sperm.

Emergency Contraception - Levonorgestrel ("Plan B") is the recommended method of

emergency contraception. This progestin-only method is considered effective up to 120 hours
(5 days) after intercourse, although effectiveness is greater the earlier the medication is
administered. There are no contraindications to the use of levonorgestrel, and no physical
exam or lab testing is required. It has the lowest incidence of side effects amongst emergency
contraceptives, although nausea (20%) and vomiting (5%) may occur. Individuals 18 years of
age or older can obtain levonorgestrel over-the-counter, whereas individuals under 18 must
obtain a prescription in most states. Levonorgestrel prevents pregnancy in approximately 7 out
of every 8 women who would have otherwise become pregnant from intercourse.
It is inappropriate to tell a woman of reproductive age not to worry because her risk of
becoming pregnant after an episode of unprotected sex is low. No matter how low the risk,
dont ask them not to worry.

Initial Menstrual Cycles in Pubertal Females are usually irregular and often anovulatory. This is
due to immaturity of the developing hypothalamic-pituitary-gonadal axis that does not
produce adequate quantities and proportions of the hormones (i.e. LH and FSH) required to
induce ovulation. In the absence of ovulation, menstrual cycles lack their regular periodicity.
The endometrium builds up under the influence of estrogen, but without the influence of
progesterone, the cue to slough the endometrium is lacking and menstrual-like bleeding occurs
due to estrogen breakthrough bleeding. Normally, progesterone is produced in increased
amounts by the corpus luteum following ovulation, and withdrawal of this progesterone as the
corpus luteum degenerates results in menses.

Primary Dysmenorrhea - Lower abdominal pain that radiates to the thighs and back and
begin hours before menstruation is classic for primary dysmenorrhea. In primary
dysmenorrheal, the release of prostaglandins during the breakdown of the endometrium is
believed to be the cause of symptoms. Women with primary dysmenorrhea have higher levels
of prostaglandins than normal. These levels can be reduced with NSAIDs which are the most
effective treatment for this condition.

Premenstrual syndrome (PMS) - The most common physical manifestations of PMS are
bloating, fatigue, headaches, and breast tenderness. Psychological symptoms may include
anxiety, mood swings, difficulty concentrating, decreased libido and irritability. Symptoms
usually begin one to two weeks prior to menses, and regress around the time of menstrual
flow. Symptoms are then typically absent until the next ovulation.

Maintaining a menstrual diary for at least 3 cycles is a useful aid for confirming the diagnosis
in suspected cases; PMS is confirmed when symptoms occur repeatedly and predictably in the
days prior to menstruation and are absent or less severe during the follicular (proliferative)
phase. If symptoms are present throughout the menstrual cycle, then other conditions such as
mood disorder are more likely.

Once the diagnosis of PMS is confirmed, treatment depends on the patient's complaints. There
is no universally accepted treatment. Reduction of caffeine intake may reduce breast
symptoms. An exercise program may be effective in improving the general well being of the
patient. In women whose symptoms are more severe and cause socioeconomic dysfunction,
selective serotonin reuptake inhibitors (SSRis) are the drug of choice. When SSRis fail to
alleviate symptoms in such patients despite therapy over multiple cycles, low dose alprazolam
is indicated. Relaxation techniques and bright light therapy have some proven effect in
management of PMS, but cognitive behavioral therapy and insight oriented and supportive
psychotherapy do not play a role. Treatment should not be initiated until the diagnosis is made.

Steroid Induced Acne - Systemic and topical corticosteroids can induce an acneiform eruption
characterized by monomorphous, erythematous follicular papules distributed on the face,
trunk and extremities. Comedones are characteristically absent.

Chlamydia is a very common cause of urethritis, cervicitis, and vaginitis. Chlamydial infection is
asymptomatic in 50% of men and 80% of women. The frequent absence of symptoms may
cause patients to go undiagnosed and untreated. Patients who lack a definitive diagnosis of
Chlamydia and go untreated are at risk of developing complications such as pelvic inflammatory
disease and infertility. They are also more likely to spread the disease to others.

Considering the frequent absence of symptoms and the degree of transmissibility, sexually
active patients should be screened regularly for chlamydia. The CDC recommends annual
screening for chlamydia in sexually active women less than 25 years old and for women > 25
years old if they have risk factors such as new or multiple sexual partners.

The nucleic acid amplification test for chlamydia is an effective screening method with a
sensitivity of 80-92% and specificity of approximately 99%. When a screening test is positive for
chlamydia, the patient as well as her sexual partners should be treated with a single dose of
azithromycin or a course of doxycycline

Nucleic acid amplification test has a sensitivity of 98-100% for the detection of gonorrhea.
Given that the test is negative for gonorrhea, treating this patient for chlamydia alone is
appropriate. Note that if nucleic acid amplification were not available, the diagnosis might be
made by Gram stain. A Gram stain performed on urethral specimens usually cannot detect
chlamydia and has a much lower sensitivity for diagnosing gonococcal infections, especially in
asymptomatic patients. In a clinical scenario where less reliable tests are used to diagnose
these infections, combination therapy for both chlamydia and gonorrhea would be indicated.

PID - Criteria for diagnosis include fever >38 C, leukocytosis, elevated erythrocyte
sedimentation rate, purulent cervical discharge, adnexal tenderness, cervical motion
tenderness, and lower abdominal tenderness.

PID is the most common cause of infertility in women age <30 with normal menstruation. If left
untreated. It may lead to tuba-ovarian abscess, abscess rupture, pelvic peritonitis, and sepsis.
The condition should be managed promptly before culture results are obtained.
Hospitalization and parenteral antibiotics are recommended for high fever, failure to respond
to oral antibiotics, inability to take oral medications due to nausea and vomiting, and
pregnancy, and for patients at risk of noncompliance (teenagers, women of low socioeconomic
status). PID is most commonly caused by Neisseria gonorrhea, Chlamydia trachomatis and
genital mycoplasmas. PID is managed with empirical wide-spectrum antibiotic therapy.

Regimens for hospitalized patients include cefoxitin or cefotetan/doxycycline and

clindamycin/gentamicin (all intravenous).

Antibiotic therapy for PID should never be delayed until culture results are obtained.

Oral Contraceptive Pills - OCPs suppress ovulation by inhibiting the release of gonadotropins
and thereby inhibiting follicular development. In addition to suppressing ovulation, OCPs have
the beneficial effects of decreasing risk for ovarian and endometrial cancer and relieving
symptoms of dysmenorrheal, endometriosis, premenstrual syndrome and menorrhagia.
Combined OCPs also often improve the regularity of menses in patients whose cycles are
irregular. However, common side effects of combined OCPs include breakthrough bleeding and
amenorrhea. In patients with amenorrhea due to OCP usage, increasing the estrogen dose
often solves the problem. Ruling out pregnancy is critical before taking this step.

OCPs offer both risks and benefits as outlined below. The risks and benefits should be weighed
carefully for each individual patient.

OCPs have been shown to cause a mild increase in insulin resistance leading to worsening of
diabetes milletus if the patient already has it. However, OCPs have not been shown to
precipitate diabetes in non-diabetic patients.

Numerous recent studies have determined that weight gain is not associated with the use of
combination oral contraceptives. Older oral contraceptive formulations were associated with
insulin resistance, which may possibly induce weight gain; but new lower dose formulations do
not carry this risk. In a systematic review (Cochrane Database 2006) of 44 trials, there was no
evidence to support a causal relationship between combination oral contraceptive use and
weight gain.

The most recent ACOG guidelines (2009) recommend beginning cervical cancer screening at age
21, regardless of onset of sexual activity. This is based on the high rates of regression of
dysplasia in adolescents, the low incidence of cervical cancer in women under 21, and the
potential side effects of colposcopy, biopsy and LEEP.

Osteoporosis Risk Factors - The risk factors for the development of osteoporosis can be
subdivided into two subgroups: modifiable and non-modifiable.

Modifiable risk factors include the following: hormonal factors such as low estrogen levels,
malnutrition, decreased calcium, decreased vitamin D, use of certain medications such as
glucocorticoids or anticonvulsants, immobility, cigarette smoking, and excessive alcohol
consumption.

Non-modifiable risk factors include female gender, advanced age, small body size, late
menarche/early menopause, Caucasian and Asian ethnicity, and a family history of
osteoporosis. Patients at risk for osteoporosis should be encouraged to make lifestyle
modifications including weight-bearing exercise, smoking cessation, and decreased alcohol
consumption.

Alcohol consumption causes a dose-dependent increase in the risk of osteoporotic fractures,

and patients have a significant increase in their fracture risk if they drink more than two drinks
daily.

Adipose tissue is a source of endogenous estrogen and obesity inherently leads to increased
weight bearing. As a result of these two factors, obesity is actually protective against the
development of osteoporosis but associated rather with osteoarthritis.

A typical lacto-ovo vegetarian diet includes foods fortified with calcium such as dairy products,
orange juice, cereals, and whole grains. In addition, certain green leafy vegetables such as
broccoli and spinach are good sources of calcium. A vegan vegetarian diet does not include
dairy products, and these patients are at risk for low Vitamin D intake and bone loss without
adequate supplementation.

Weight-bearing exercise, like brisk walking, is associated with a small improvement in bone
mineral density and is recommended to help prevent osteoporosis.
Raloxifene is a mixed agonist/antagonist of estrogen receptors. In breast and vaginal tissue, it is
an antagonist, whereas in bone tissue, it is an agonist. It is a first-line agent for the prevention
of osteoporosis, and it decreases breast cancer risk. It increases the risk of thromboembolism.

Polycystic Ovary Syndrome (PCOS) This condition should be suspected in any patient who has
menstrual irregularities and evidence of hyperandrogenism. Symptoms of PCOS may appear at
any time in a woman's life, though many times "appear" when patients discontinue hormonal
contraception; thus accounting for many patients presenting later in life. Polycystic ovarian
syndrome diagnosis includes the presence of any two of the following three signs and
symptoms (Rotterdam Criteria 2003)

1. Clinical (i.e., hirsutism, acne, or male pattern baldness or "androgenic alopecia") and/or
biochemical (i.e., high serum androgen concentrations) hyperandrogenism.

2. Amenorrhea or oligomenorrhea.

3. Pelvic ultrasound with cystic ovaries; small cysts are noted around the ovaries in a
classic "string of pearls" appearance.

50% of PCOS patients are found to be obese. These patients are also at risk of developing
infertility, insulin resistance, type II diabetes, cardiovascular disease, and endometrial cancer.
A standard 2-hour oral glucose tolerance test (OGTT) identifies most patients with impaired
glucose tolerance and early type 2 diabetes better than a fasting glucose alone. An OGTT is
recommended by the American College of Obstetrics and Gynecology in the workup of a
patient with PCOS.

PCOS results from abnormal GnRH secretion that stimulates the pituitary to secrete excessive
luteinizing hormone (LH) and insufficient follicle stimulating hormone (FSH). Excess LH
stimulates excess androgen production by ovarian theca cells resulting in hirsutism, male
escutcheon, acne and androgenic alopecia. Anovulation is caused in part by imbalances in LH
and FSH production and in part by insulin resistance in these patients. Anovulation in this
condition can be associated both with amenorrhea and irregular menses occasionally
complicated by menometrorrhagia.

Type II diabetes and impaired glucose tolerance are common findings in patients with PCOS. A
glucose tolerance test is recommended in all patients diagnosed with PCOS as it is more
sensitive in detecting abnormal glucose metabolism than a fasting glucose. A Two-hour glucose
of > 140 mg/dl on glucose tolerance test is presumptive of insulin resistance and > 200 is
consistent with diabetes mellitus. Life style modification, oral contraceptive or clomiphene
(depending on desire to conceive), and antiandrogen agents may be used as treatment. In
addition, metformin is indicated in women with polycystic ovarian syndrome and impaired
glucose tolerance. The benefits of metformin use in polycystic ovarian syndrome are as follows:
 1. It helps prevent type 2 diabetes mellitus.

2. Helps losing weight (most of the patients with polycystic ovarian syndrome are obese).

3. In conjugation with clomiphene citrate, it helps to induce ovulation in infertile

polycystic ovarian syndrome patients with anovulation; however, it is not FDA
approved to be used just for this purpose. If the women desires fertility, give
Clomophene,

4. It has modest effect in suppressing androgen production and, thus, helps correct
hirsutism to some extent.

Women with PCOS are oligo- or anovulatory and are deficient in progesterone secretion; thus,
they usually have a constant and unbalanced mitogenic stimulation of the endometrium by
estrogens leading to endometrial hyperplasia, intermittent breakthrough bleeding and
dysfunctional uterine bleeding. This unopposed estrogen stimulation leaves them at increased
risk for endometrial cancer.

Endometriosis Endometriosis is a benign condition where foci of endometrial glandular and

stromal tissue are found in locations outside the uterus. These foci react to hormonal stimuli in
the same manner as the endometrium does, and thus increase in size throughout the menstrual
cycle and bleed when the hormonal stimuli is suspended. The most frequently affected sites
are the ovaries, the peritoneal surfaces of the cul-de-sac, the broad and uterosacral ligaments
and the rectovaginal septum, but any site including the bladder, intestine and skin may be
involved though far less commonly.

Patients with endometriosis may frequently be asymptomatic, but when symptoms are
present, they typically include chronic pelvic pain & low sacral back pain that is worse in the
premenstrual period, dysmenorrhea and pain with sexual intercourse or defecation (3Ds
Dysmenorrhea, Dyspareunia & Dyschezia). Examination may reveal rectovaginal tenderness,
posterior vaginal fornix tenderness, tender adnexal mass or firm nodularity in the broad
ligaments, the uterosacral ligament or in the cul-de-sac & tenderness with movement of the
uterus (Not cervical motion tenderness) due to the presence of ectopic endometrial tissue in
the rectovaginal septum and the pelvic peritoneum.

Ultrasound examination may demonstrate homogenous endometriomas on the adnexae or

within the peritoneal or pelvic regions. The diagnosis can only be made with certainty by
laparoscopic examination of the pelvis and peritoneum.

Laparoscopy is the gold standard for making the diagnosis of endometriosis.

Patients with endometriosis are at an increased risk of decreased fertility or infertility. Up to
30% of females being evaluated for infertility are found to have endometriosis. Possible
mechanisms for impaired fertility in these patients include adhesion formation within the
peritoneum that interferes with the normal transfer of oocytes from the ovarian surface to the
fallopian tubes, endometrial factors within the uterus that may provide a suboptimal
environment for implantation and hormonal issues that have yet to be determined that may
affect ovarian function.

Various treatment options exist for endometriosis, with one of the most popular being
combined estrogen and progestin pills (OCPs). Other possibilities include GnRH analogs (eg.
leuprolide) or danazol.

Ovarian Problems

Premature Ovarian Failure - Premature ovarian failure is characterized by amenorrhea,

hypoestrogenism and elevated serum gonadotropin levels in women age < 40 years. The
amenorrhea only needs to be of 3 months duration with FSH in menopausal range (defined by
lab assay) to meet the diagnostic criteria. It is not necessary to wait an entire year for
amenorrhea, as early diagnosis is important to prevent osteoporosis at a young age. Premature
ovarian failure may be secondary to accelerated follicle atresia or a low initial number of
primordial follicles. It is most commonly idiopathic but may also be due to mumps, oophoritis,
irradiation, or chemotherapy. It can be associated with autoimmune disorders such as
Hashimoto's thyroiditis, Addison's disease, type I diabetes mellitus and pernicious anemia.
Presence of these disorders supports the hypothesis that some cases of idiopathic premature
ovarian failure are of autoimmune origin.

Women present with signs and symptoms similar to those seen in menopause. The diagnosis is
confirmed by demonstrating increased serum FSH and LH levels and decreased estrogen levels.
The elevation of FSH is generally greater than that of LH. So the FSH:LH ratio is >1.0. Patients
with premature ovarian failure lack viable oocytes, so the only option available to allow
pregnancy is in vitro fertilization using donor oocytes.

Menopause vs Hyperthyroidism - These patient experience night sweats, Insomnia, and

irregular menses. The differential diagnosis for these symptoms in middle-aged women
includes menopause and hyperthyroidism, and it is appropriate to obtain serum TSH and FSH
levels.

Hyperthyroidism has a myriad of clinical symptoms including heat intolerance, sweating,

irregular menses, tremor, weight loss, hyperreflexia, diarrhea, and palpitations. A decreased
TSH is consistent with a diagnosis of hyperthyroidism.
Clinical signs of menopause, which occurs in women at an average age of 51, include irregular
or absent menses, heat intolerance, flushing, insomnia, headaches and night sweats. During
menopause, the circulating estrogen level decreases, resulting in a decrease in the feedback
inhibition on the hypothalamic-pituitary axis. This results in the elevation of serum FSH and LH
levels

During childbearing years, estrogens are mainly formed through the conversion of androgens
by the enzyme aromatase, which is primarily present in granulosa cells of the ovary. Peripheral
fat tissue also contains the enzyme aromatase to a lesser degree. After menopause, aromatase
activity in the ovaries ceases and the only remaining tissue with aromatase activity is the
peripheral fat. Patients who are obese have more peripheral fat; and therefore, will have more
estrogen formation. This increased estrogen formation may help to alleviate many of the typical
menopausal symptoms, such as vaginal dryness or dyspareunia. It may also be making her hot
flashes milder in intensity as well.

Aromatase in peripheral fat is responsible for Conversion of adrenal androgens to estrogens.

Uterine Problems

Endometrial Hyperplasia - Premenopausal women with simple or complex hyperplasia without

atypia respond to therapy with cyclic progestins. All patients should undergo repeat biopsy
after 3-6 months of treatment. The risk of progression to endometrial cancer in patients with
complex hyperplasia WITHOUT atypia is low (3% ); and therefore. Even if this patient does not
want more children. Hysterectomy is not warranted. This patient is also a poor surgical
candidate given her comorbid conditions. and her risk of complications from surgery is likely to
be higher than 3%.

one way to remember these rates (approximately) is to picture the progression list above and
think "penny, nickel, dime, and quarter."

Anovulatory Cycles - In a young patient that has only recently experienced menarche, heavy
menses with an irregular cycle can be attributed to anovulatory cycles. Females in this age
group have an immature hypothalamic-pituitary-ovarian axis that may fail to produce
gonadotropins (LH and FSH) in the proper quantities and ratios to induce ovulation. Up to 90%
of all menstrual cycles in the first year after menarche may be anovulatory. Because the
endometrium is responsive to baseline estrogen levels during the females cycle, the
endometrium will develop and eventually slough resulting in some cyclic bleeding due to a
breakthrough phenomenon.

Uterine Fibroids - The presence of dysmenorrheal, heavy menses and an enlarged uterus which
causes a dull/pulling sensation in the pelvis is classic for uterine fibroids. Submucosal fibroids
often interfere with implantation of the embryo, resulting in infertility. Fibroids are the most
common benign uterine tumors in women and the most common indication for hysterectomy.
They are estrogen- dependent tumors; therefore, they increase in size with oral contraceptive
pills ( OCPs) or pregnancy, and often regress after menopause.

Vaginal Problems

Vaginal Discharge - Symptoms of pathologic vaginal discharge include a history of pruritus,

burning, and malodorous vaginal discharge. Vaginal exam findings which raise suspicion for a
pathologic cause include erythema, edema and friability of the vaginal mucosa; tenderness of
the cervix; and green or curd-like vaginal discharge. However, copious vaginal discharge by
itself is not necessarily pathologic. The amount of vaginal discharge can vary between women,
and even a given woman can have significant variation in the amount of vaginal discharge at
different stages of the menstrual cycle.

Copious vaginal discharge that is white or yellow in appearance, nonmalodorous, and occurs in
the absence of other symptoms or findings on vaginal exam is referred to as physiologic
leucorrhea. It does not require treatment, and women with this condition should receive
reassurance.

Candida vaginitis causes a discharge that is non-malodorous, white and thick in consistency.
The pH of the discharge is usually between 4.0 and 4.5. Pseudohyphae are characteristically
seen on wet mount preparations of vaginal discharge from patients with Candida vulvovaginitis.
Symptomatic patients can be treated with an azole antifungal, such as fluconazole. Sexual
partners do not require treatment.

Trichomonas vaginitis It is a sexually transmitted infection that causes malodorous, gray-

green, THIN, frothy vaginal discharge, as well as vaginal and vulvar pruritus, Dysuria, and
dyspareunia. Trichomonas infection often disrupts the normal vaginal milieu, causing pH
increases to the 5.0 - 6.0 range.

Vs
Bacterial Vaginosis - The diagnosis of bacterial vaginosis (BV) is made when three of the four
Amsel criteria are met. The Amsel criteria are as follows:

1) THIN, gray-white vaginal discharge

2) Vaginal pH > 4.5
3) A positive "whiff" test upon addition of KOH to the vaginal discharge
4) "Clue cells" (vaginal epithelial cells with adherent coccobacilli) on wet mount

Pruritus and inflammation are NOT characteristic. Treatment with metronidazole is

appropriate.

Atrophic vaginitis is a clinical diagnosis made based on history and physical exam findings.
Typical symptoms include vaginal dryness, pruritus, dyspareunia, dysuria, and urinary
frequency. Pelvic exam in atrophic vaginitis is characterized by pale, dry and smooth vaginal
epithelium, scarce pubic hair, and loss of the labial fat pad. This condition occurs in post-
menopausal females as a result of decreased estrogen levels. Many symptoms of atrophic
vaginitis can also be seen in urinary tract infection (UTI). Use of moisturizers and lubricants is an
appropriate first step in management of mild atrophic vaginitis; for moderate to severe cases
the first-line treatment is local low-dose vaginal estrogen therapy.

Diethylstilbestrol (DES) is a synthetic preparation possessing estrogen properties, which was

widely used between 1947 and 1971 for treatment of threatened abortion. Female offspring of
women who used DES during their pregnancy are at increased risk of developing clear cell
adenocarcinoma of the vagina and cervix. These women also exhibit cervical abnormalities
(hypoplasia), uterine malformations (T-shaped I small uterine cavity), vaginal adenosis and
vaginal septae. Many have difficulty conceiving and maintaining pregnancy. Males exposed in
utero are at risk of cryptorchidism, microphallus, hypospadias and testicular hypoplasia.
Genital warts (condyloma acuminata) are caused by human papilloma virus (HPV) infection.
Patients may present with internal and/or external vaginal lesions as well as anogenital lesions.
Genital warts typically appear as clusters of pink or skin-colored lesions with a smooth,
teardrop appearance. Patients are most often asymptomatic, although pruritus, pain, and
bleeding are all possible. Diagnosis can be made based solely on the characteristic appearance
of the lesions, although application of acetic acid (condyloma acuminata lesions turn white)
and/or biopsy may be used to support the diagnosis. Treatment of genital warts depends on
the size of the lesions. Small lesions may be treated in the office with trichloroacetic acid or
podophyllin. Larger lesions are often treated with excision or fulguration (electric current).
Regardless of the method of treatment, rates of recurrence are high.

Pap Smear

CIN I in a low risk patient with a low-grade lesion on Pap smear can be expectantly managed
with either repeat Pap smear screening at 6 and 12 months or HPV testing at 12 months.
Positive results on either of these tests should be evaluated with repeat colposcopy.

LSIL on Pap Smear - Current guidelines recommend Pap smears for all women, starting at the
age of 21 years. Management of a low-grade squamous epithelial lesion (LSIL) differs based on
the age of the patient. An LSIL discovered on cervical cytology generally indicates the presence
of cytologically atypical squamous cells in the cervix. The atypical cells can be due to human
papillomavirus (HPV) infection or cervical intraepithelial neoplasia ( CIN), which is graded as
type 1-3 based on histology. The majority of the LSIL lesions that are not due to HPV infection
are usually CIN 1, which usually does not require any immediate treatment except observation.
Given the high risk (nearly 15%) of CIN 2 or 3 in premenopausal adult women, LSIL should be
followed by colposcopy in order to biopsy the lesion.
Postmenopausal women can be managed with one of three options: immediate colposcopy,
reflex HPV testing or repeated Pap smear at 6 and 12 months. Reflex HPV testing is a useful
option in determining the need for colposcopy given the relatively low incidence of HPV in this
population. If the HPV test is negative, the patient may have a repeated Pap smear at 12
months. If the HPV test is positive, then she needs an immediate colposcopy. If the initial option
of repeated Pap smears at 6 and 12 months is chosen and the results are abnormal, then the
patient should also undergo colposcopy.

Cervical dysplasia in a high-risk adult woman should be investigated with colposcopy.

Esrtogen Replacement Therapy & Thyroid Medication - The requirement for L-thyroxine in
patients receiving estrogen replacement therapy increases. The potential causes may include
induction of liver enzymes, increased level of TBG, and an increased volume of the distribution
of thyroid hormones. In pregnancy, also, thyroid hormone requirements will be increased, and
the patient should be monitored every 4-6 weeks for dose adjustments.

Precocious Puberty Precocious puberty is defined as the development of secondary sex

characteristics before the age of 8 in girls and 9 in boys. Accelerated bone growth and advanced
bone age are also common.
The causes of precocious puberty can be broken into two categories: central and peripheral.
Central precocious puberty is the result of early activation of the hypothalamic-pituitary-
ovarian (HPO) axis. Therefore, FSH and LH levels are elevated in central precocious puberty.

In contrast, patients with peripheral precocious puberty present with low FSH and LH levels.
Whereas central precocious puberty is caused by GnRH activation, peripheral precocious
puberty is caused by gonadal or adrenal release of excess sex hormones.

There are multiple forms of congenital adrenal hyperplasia (CAH), each of which may present
with a specific pattern of findings. CAH is a cause of peripheral precocious puberty. Affected
patients have low FSH and LH levels.

Idiopathic central precocious puberty, which is the most common type in females, results from
the premature activation of the hypothalamic-pituitary-gonadal axis. Patients with central
precocious puberty have pubertal levels of basal LH that increase with GnRH stimulation,
whereas patients with a peripheral source of precocious puberty, such as in certain ovarian
pathologies, have low LH levels with no response to GnRH. All patients with central precocious
puberty should have brain imaging to rule out an underlying CNS lesion.

GnRH Stimulation leads to increased LH = Central Precocious Puberty

GnRH Stimulation leads to No increase in LH = Peripheral Precocious Puberty.

Idiopathic central precocious puberty is managed with GnRH agonist therapy in order to
prevent premature fusion of the epiphyseal plates, which would otherwise lead to a short
stature.

Granulosa cell tumors are fairly common and represent 10% of all solid malignant ovarian
tumors. They can occur at any age, but usually follow a bimodal age distribution. When
occurring before puberty, Precocious puberty is often the presenting feature. The clinical
features depend upon the estrogenic activity of the tumor. The tumor produces excessive
amounts of estrogen and causes isosexual precocious puberty. Individuals develop secondary
sexual characteristics, hypertrophy of breasts and external genitalia, pubic hair growth, and
hyperplasia of the uterus. Usually, removal of the tumor causes regression of all these
symptoms.

When this tumor occurs in postmenopausal women, it is manifested as postmenopausal

bleeding, and the uterus shows myohyperplasia. Patients can develop estrogenic features such
as hypertrophy of the breasts and absence of postmenopausal signs (i.e. absence of vaginal
atrophy).
Turners syndrome Always suspect Turners syndrome when a girl of short stature presents
with any of the feature of turners syndrome like widely spaced nipples, shield chest, bicuspid
aortic valve, coarctation of aorta, streak gonads & defective lymphatics. Patients with Turner
syndrome have ovarian dysgenesis, which results in low estrogen levels and inability to
menstruate. The poor ovarian function causes FSH levels to be high due to lack of negative
feedback.

Primary Amenorrhea Isolated amenorrhea with well-developed secondary sexual

characteristics can be considered normal up to the age of 16. However, if secondary sexual
characteristics are absent, work-up should not be delayed beyond age 14.

A patient, who has a female phenotype but lacks a normal vagina and uterus, narrows the
etiology of her primary amenorrhea to mullerian agenesis, androgen insensitivity, or 5-alpha-
reductase deficiency.

The karyotype is the determining test, with both androgen insensitivity and 5-alpha-reductase
deficiency being seen in patients with a XY genotype. If the genotype is XX, its mullerian
agenesis as the best explanation for her condition. The mullerian duct normally leads to the
development of the proximal vagina and the uterus; therefore patients with mullerian agenesis
normally have a blind ended vagina with little to no uterine tissue.

Patients with 5-alpha-reductase deficiency cannot convert testosterone to the more potent
dihydrotestosterone (DHT). They have a male XY genotype and female external genitalia, but
typically show virilization at puberty.

Aromatase deficiency is a rare genetic disorder marked by either total absence or poor
functioning of the enzyme that converts androgens into estrogens. Its consequences are
numerous. In utero the placenta will not be able to make estrogens, leading to masculinization
of the mother that resolves after delivery. The high levels of gestational androgens result in a
virilized XX child with normal internal genitalia but ambiguous external genitalia.

Clitoromegaly is often seen when excessive androgens are present in utero. Later in life
patients will have delayed puberty, osteoporosis, undetectable circulating estrogens, high
concentrations of gonadotropins and polycystic ovaries.

High FSH/LH with low estrogen, & increased Androgens is consistent with aromatase
deficiency.
Primary amenorrhea can be due to either hypothalamic/pituitary (central) abnormalities, or to
gonadal (peripheral) abnormalities. This distinction can be made by measurement of the FSH
level. Increased FSH (hypergonadotropic amenorrhea) indicates a peripheral cause, and
decreased FSH (hypogonadotropic amenorrhea) indicates a central cause. If the amenorrhea is
of central origin, a pituitary MRI is indicated to look for a lesion in the sella turcica. If
amenorrhea is of peripheral origin, karyotyping would be the next step.

In a patient with primary amenorrhea:

FSH measurement should be ordered if there is no breast development

Pituitary MRI is the next step if FSH is decreased
Karyotyping is the next step if FSH is increased

The combination of primary amenorrhea, bilateral inguinal masses, and breast development
without pubic or axillary hair is strongly suggestive of androgen insensitivity syndrome. This
condition is related to a mutation of the androgen receptor (AR) gene making peripheral tissues
unresponsive to androgens that are typically available in normal concentrations in these
patients. Although the genotype is 46, XY, the patient will be phenotypically female; this is also
known as a male pseudohermaphrodite. Breast development is present because testosterone is
converted to estrogen, but there is little or no pubic or axillary hair. No mullerian structures are
present (uterus. fallopian tubes) and the vagina ends with a blind pouch. Testes can be
documented with abdominal ultrasonogram in the inguinal canal or in the labia.

Because of increased (5%) risk for testicular carcinoma, which typically develops in the second
or third decade, a gonadectomy is indicated in these patients. With androgen insensitivity,
gonadectomy should not be completed until after completion of breast development and
attainment of adult height.

A gonadectomy should be performed after completion of puberty to avoid the risk of testicular
carcinoma.

Kallmann's syndrome consists of a congenital absence of GnRH secretion (i.e.

Hypogonadotropic hypogonadism) associated with anosmia. Patients have a normal XX
genotype and normal female internal reproductive organs. They present with primary
amenorrhea and absent secondary sexual characteristics such as breast development and pubic
hair; the addition of anosmia to the presentation may suggest the diagnosis. Abnormal
development of the olfactory bulbs and tracts result in hyposmia or anosmia (decreased sense
of smell). The FSH and LH levels are low, in contrast to the levels in primary ovarian failure
which are usually elevated.

Secondary Amenorrhea

In any woman of childbearing age with secondary amenorrhea, first rule out pregnancy.

The first step is to rule out pregnancy and look for clues on history and physical examination to
suggest one of the above etiologies. The lack of stress in the patient makes hypothalamic
causes less likely, and a normal uterine examination makes Asherman syndrome less likely.
Initial laboratory testing should include FSH to rule out ovarian failure, prolactin to evaluate for
hyperprolactinemia, and TSH to evaluate for hypothyroidism and hyperthyroidism. Prolactin
production is inhibited by dopamine and stimulated by serotonin and TRH. Causes of increased
prolactin include dopamine antagonists (e.g .. antipsychotics. tricyclic antidepressants. and
monoamine oxidase inhibitors) and hypothalamic and pituitary tumors.
Hypothyroidism can also elevate the prolactin level, but the mechanism is unclear. It is thought
that enhanced synthesis of TRH in the hypothalamus results in an increased pituitary response
to secrete prolactin, which sometimes causes symptoms such as galactorrhea. As a result,
obtaining the TSH and T4 levels is always recommended before interpreting the prolactin level.
If the TSH and T4 levels are both low, then a TRH level can be ordered to confirm secondary
hypothyroidism.

Hypogonadotropic hypogonadism can result from strenuous exercise, anorexia nervosa,

marijuana use, starvation, stress, depression and chronic illness. Aside from amenorrhea,
hypogonadotropic hypogonadism has several other complications. As FSH and LH drop, so too
do sex hormones like estrogen and testosterone. This predisposes patients to osteoporosis and
decreased muscle bulk. Patients will also often suffer from infertility.
Amenorrhea due to Antipsychotics - Risperidone is an atypical antipsychotic commonly used to
treat schizophrenia and bipolar disorder. It is a dopamine antagonist that also acts on serotonin
receptors. It inhibits dopamine, which leads to elevated serum prolactin levels. The
hyperprolactinemia causes several symptoms, including oligomenorrhea, amenorrhea and
galactorrhea, in premenopausal females. Risperidone (Ras) has been found to increase
prolactin levels to a greater extent than do many of the other antipsychotics. The resultant
side effects can include the breast tenderness, amenorrhea, and galactorrhea. Significant
weight gain can also occur with antipsychotic therapy.

Dysfunctional Uterine Bleeding (DUB) refers to heavy vaginal bleeding during menses & inter
menstural bleeding that occurs in the absence of structural or organic disease. These women
have a normal pelvic exam and negative pregnancy test.

Patients with dysfunctional uterine bleeding (DUB) have lost cyclic endometrial stimulation that
arises from the ovulatory cycle. As a result, these patients have constant, noncycling estrogen
levels that stimulate endometrial growth. Proliferation without periodic shedding causes the
endometrium to outgrow its blood supply. The tissue breaks down and sloughs from the uterus.
Subsequent healing of the endometrium is irregular and dyssynchronous.

DUB is most often the result of anovulation. In adolescent females with DUB, the proper
treatment depends on the severity of bleeding. If DUB is mild, then iron supplementation is
sufficient. If DUB is moderate and there is no active bleeding, then progestin should be added.
If DUB is moderate with active bleeding, or if DUB is severe & ACTIVE vaginal bleeding is
occuring, then high dose estrogen is indicated

Endometrial biopsy is required in selected patients to rule out endometrial hyperplasia or

carcinoma. These patients include those who are > 35 years of age, obese, chronically
hypertensive, or diabetic. If biopsy is negative for hyperplasia or carcinoma, then she can be
treated with cyclic progestins. Endometrial ablation or hysterectomy is indicated only if
hormonal therapy fails.

Da fuq?

Stress Incontinence - Stress incontinence is a common cause of incontinence in older women,

high parity being one of the major risk factors. A high number of vaginal deliveries may lead to
pelvic floor muscle weakness over a period of time. Stress incontinence is characterized by the
loss of small amounts of urine with increased intra-abdominal pressure, as occurs with
laughing, coughing, or sneezing. Urine leakage results from ineffective closure of the urethral
sphincter. This ineffective sphincter closure often results from weakening of the pelvic floor
musculature, leading to urethral hypermobility. Urethral hypermobility may be diagnosed by
inserting a cotton swab into the urethral orifice and demonstrating an angle of > 30" upon an
increase in intra-abdominal pressure. Pregnancy, childbirth, menopause, and obesity are all risk
factors for stress incontinence. This patient has the classic signs and symptoms of stress
incontinence. Kegel exercises should be advised in all patients with stress incontinence to
restore pelvic floor strength, but the most beneficial treatment for these patients is restoration
of the urethrovesical angle by urethropexy.

Urge Incontinence - Detrusor instability, bladder irritation from a neoplasm, and interstitial
cystitis result in urge incontinence, which causes sudden and frequent loss of moderate to large
amounts of urine. This is often accompanied by nocturia and frequency.

Overflow Incontinence - Diabetic neuropathy causes overflow incontinence, which is

characterized by loss of small amounts of urine from an over distended bladder, and a markedly
increased residual volume. Patients usually have a long history of diabetes that is not well
controlled.

Interstitial cystitis (IC) is a chronic condition of the bladder of uncertain etiology and
pathophysiology. It is clinically characterized by the triad of urinary urgency and frequency as
well as chronic pelvic pain in the absence of another disease that could cause the symptoms.
Pelvic pain is occasionally the presenting symptom or chief complaint. The pelvic pain in
interstitial cystitis is classically exacerbated by sexual intercourse, filling of the bladder,
exercise, spicy foods and certain beverages. The pain is typically relieved by voiding.
Cystoscopy classically demonstrates submucosal petechiae or ulcerations.

Vaginismus is caused by involuntary contraction of the perineal musculature. The underlying

cause is psychological. Patients often have had strict religious upbringings in which sex was
either not discussed or discussed in a negative fashion, or have had traumatic childhood
experiences which have left them fearful of vaginal penetration. Vaginismus is most often
diagnosed in teenagers and young adult females. Treatment for vaginismus is effective with
success rates of 80% or better. Typically, treatment includes relaxation, Kegel exercises (to
relax the vaginal muscles), and insertion of dilators, fingers. etc. to bring about desensitization.

Lichen sclerosus (lichen sclerosus et atrophicus. LS&A) is a chronic inflammatory condition of

the anogenital region that most commonly affects women. This condition may have an
autoimmune pathogenesis. It is characterized clinically by anogenital discomfort including
pruritus, dyspareunia, dysuria and painful defecation. Physical examination reveals porcelain-
white polygonal macules and patches with an atrophic. "cigarette paper" quality. Sclerosus
and scarring can lead to obliteration of the labia minora and clitoris and a decrease in the
diameter of the introitus. While the diagnosis can readily be made clinically, vulvar squamous
cell carcinoma (SCC) occurs more commonly in women with LS&A. When the diagnosis is in
question, punch biopsy of any suspicious lesions should be performed.

LS&A is one of the few conditions for which use of high-potency topical steroids on the genitals
is encouraged. A class I topical corticosteroid in ointment form should be applied twice daily for
four weeks. At which point transition to a less potent topical steroid or topical calcineurin
inhibitor for maintenance therapy is appropriate.

Vaginal SCC - SCC is the most common form of vaginal cancer, and risk for SCC of the vagina
increases with age (most common in women >60 years of age). The most common symptoms
are vaginal bleeding and malodorous vaginal discharge. Definitive diagnosis is made by
biopsy. Treatment of vaginal cancer depends on staging.

Stage I and II tumors (no extension to the pelvic wall and no metastases) which are less than 2
cm in size may be removed surgically.

Stage I and II tumors which are greater than 2 cm in size are treated with radiation therapy.

Combination chemotherapy is used for Stage III and IV tumors as well as tumors greater than 4
cm in size.

Breast

Mammography is used both in screening for breast cancer, and in evaluating certain cases of
breast lump or nipple discharge.

Ultrasonogram is one test that can be used in the evaluation of a breast mass. It is most useful
at discerning fluid-filled masses from solid masses, evaluating the denser breast tissue of
younger women, and in guided biopsies.

Cytologic examination is indicated in cases of uniductal and guaiac positive nipple discharge. It
allows the pathologist to examine cells from the duct to distinguish carcinoma, proliferative
changes, and inflammatory processes.

A self-palpated breast mass is a very common clinical presentation of various benign and
malignant breast diseases. Unfortunately, it is usually very difficult to differentiate a benign
breast mass from cancer by history and physical examination. Further work-up is frequently
necessary.
A young woman who presents with a breast lump can be asked to return after her menstrual
period for reexamination if no obvious signs of malignancy are present. If the mass decreases
in size after the menstrual period, the probability of a benign disease is very high. Otherwise, it
is advisable to proceed with ultrasonography, fine needle aspiration biopsy and/or excisional
biopsy. Mammography is usually not helpful in interpreting the mass because the density of
breast tissue is high in young women

Galactorrhea presents as bilateral nipple discharge that is most often milky or clear in color,
but can also be yellow, brown, or green. Further evaluation for the causes of galactorrhea
should thus be pursued in this patient via testing of serum prolactin and TSH levels.

The red flags to watch out for in cases of nipple discharge are unilateral secretion, guaiac
positive fluid and breast lump. In the case of bilateral guaiac negative discharge, and in the
absence of a breast mass, mammography is not necessary.

Pagets disease of the Breast - Breast cancer should be considered as a possibility whenever a
patient without a prior history of skin disease develops a breast rash that is nonresponsive to
standard treatments. When severe, ductal carcinoma can infiltrate into the dermal lymphatics
with resulting edema, erythema, and warmth of the entire breastthat is known as inflammatory
carcinoma. When the rash is localized to the nipple and has an ulcerating eczematous
appearance, the primary consideration should be Paget's disease of the breast. Approximately
85% of patients with Paget's disease of the breast have an underlying breast cancer. Most of
these are either palpable or associated with a mammographic abnormality, although some may
be occult to physical exam and mammography. A skin biopsy will typically demonstrate large
cells that appear to be surrounded by clear halos because the cancer cells become retracted
from adjacent keratinocytes. Most patients with Paget's disease of the breast have an
underlying adenocarcinoma, with the changes of Paget's disease thought to be caused by
migration of neoplastic cells through the mammary ducts to the nipple surface.

Invasive Ductal Carcinoma - An important factor for both prognosis and treatment is the
presence of overexpression in the HER2 oncogene, which occurs in approximately 20% of
primary cancers. The level of HER2 expression can be determined either by fluorescent in situ
hybridization (FISH) or immunohistochemical (IHC) staining. The presence of HER2
overexpression allows one to treat with trastuzumab, also known as Herceptin, which
specifically targets cells that overexpress the oncogene. The presence of HER2 overexpression
may also alter the chemotherapy regimen used, with these patients having a more positive
response to anthracyclines. While the presence of HER2 overexpression was previously
associated with a poorer outcome, these studies were before the usage of targeted therapies
and now the prognosis of treated patients with HER2 overexpression is less clear.
Risk factors for endometrial carcinoma include advancing age, use of unopposed estrogen in
the past, prolonged use of tamoxifen, obesity, nulliparity and polycystic ovarian syndrome
(Stein-Leventhal syndrome).

Risk factors for breast cancer include a positive family history, mutations in BRCA1, BRCA2 or
p53, early menarche, late menopause, prolonged hormone replacement therapy, nulliparity
and uncommon genetic diseases such as Cowden syndrome and ataxia-telangiectasia.