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 nondiabetic 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 nonmodifiable.
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)
2)
3)
4)

THIN, gray-white vaginal discharge

Vaginal pH > 4.5
A positive "whiff" test upon addition of KOH to the vaginal discharge
"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 46 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 hypothalamicpituitary-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 intraabdominal 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 intraabdominal 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.