Endo-Reproductive Women

Question 1

What is the definition of primary amenorrhea?

Answer 1

Primary amenorrhea is the absence of menses by age 16 years accompanied by normal sexual hair pattern and normal breast development.

Question 2

What must be ruled out prior to working up for primary amenorrhea?

Answer 2

Pregnancy!

Question 3

What is the most common cause of primary amenorrhea?

Answer 3

Turner’s Syndrome (50% have this).

Approximately 15% of patients presenting with primary amenorrhea may have an anatomic abnormality of the uterus, cervix, or vagina such as müllerian agenesis, transverse vaginal septum, or imperforate hymen.

Question 4

What is the definition of secondary amenorrhea?

Answer 4

Secondary amenorrhea is the absence of a menstrual cycle for three cycles or 6 months in previously menstruating women.

Question 5

What is the most common cause of a secondary amenorrhea?

Answer 5

pregnancy

Question 6

What is Asherman Syndrome?

Answer 6

It is a cause of secondary amenorrhea. Asherman syndrome is an uncommon complication of dilation and curettage, intrauterine device placement, or surgical procedures such as hysteroscopic myomectomy; it is caused by lack of basal endometrium proliferation and formation of adhesions (synechiae).

Question 7

For secondary amenorrhea, what is the order for workup?

Answer 7

1. exclude pregnancy
2. look for structural changes (Ashermans?)
3. hormonal evaluation
4. if all negative, then progesterone challenge test

Question 8

Hormonal changes for hypogonadotropic hypogonadism? What source is suggested?

Answer 8

LOW estradiol and inappropriately NORMAL FSH and LH

-points to a central cause (hypothalamic-pituitary)

Question 9

Hormonal changes for hypergonadotropic hypogonadism? What source is suggested?

Answer 9

LOW estradiol in the setting of ELEVATED FSH and LH levels indicates hypergonadotropic hypogonadism and points to ovarian insufficiency.

Question 10

What is the most common hormonal cause of secondary amenorrhea that is not pregnancy?

Answer 10

secondary amenorrhea is polycystic ovary syndrome (PCOS) which accounts for 40% of cases.

Question 11

Risk factors for central secondary amenorrhea?

Answer 11

Risk factors include low BMI and low body fat percentage, rapid and substantial weight loss or weight gain, eating disorders, excessive exercise, severe emotional stress, or acute and chronic illness. FSH and LH levels are inappropriately low in HA but may be inappropriately normal in FHA.

Question 12

How does hyperprolactinemia and hypothyroidism cause secondary amenorrhea?

Answer 12

Hyperprolactinemia causes secondary amenorrhea through direct inhibition of GnRH secretion. Treatment of the cause of hyperprolactinemia typically results in restoration of menses. Hypothyroidism may cause secondary amenorrhea through increased thyrotropin-releasing hormone levels, which causes stimulation of prolactin secretion.

Question 13

What is the definition of primary ovarian insufficiency? What are some possible causes?

Answer 13

Hypergonadotropic hypogonadism as a result of POI is defined as amenorrhea before age 40 years in the setting of two elevated FSH levels (>40 mU/mL [40 U/L]) more than 1 month apart. Possible causes include Turner mosaicism (in which secondary amenorrhea may occur due to POI), fragile X premutation, chemotherapy or radiation, and autoimmune oophoritis.

Question 14

What is the management of hypergonadotropic hypogonadism?

Answer 14

• Estrogen replacement to prevent bone loss

- Estrogen can induce ovulation, contraception should be discussed… with cyclic progesterone

Question 15

How do you workup primary and secondary amenorrhea?

Answer 15

After excluding pregnancy, the laboratory evaluation of primary and secondary amenorrhea includes measurements of prolactin, follicle-stimulating hormone, luteinizing hormone, estradiol, and thyroid-stimulating hormone.

If hormonal evaluation for amenorrhea is negative, the next step is a progesterone challenge test; if the patient bleeds within 1 week of completing 7 to 10 days of progesterone, estrogen deficiency is not the cause and PCOS should be considered

Question 16

Describe how a progesterone test works in workup for primary/secondary amenorrhea. What does is reveal?

Answer 16

If hormonal evaluation for amenorrhea is negative, the next step is a progesterone challenge test; if the patient bleeds within 1 week of completing 7 to 10 days of progesterone, estrogen deficiency is not the cause and PCOS should be considered

Question 17

If hirsutism is present, what should someone be assessed for?

Answer 17

When hirsutism is present, the patient should be assessed for virilization, or development of male characteristics. Rapid onset and progression of deepening of the voice, severe acne, clitoromegaly, and male pattern balding are signs of virilization and are concerning for an ovarian or adrenal tumor.

Question 18

Virilization after the age of 30 is suggestive of what?

Answer 18

Age of onset after 30 years is also a risk factor for an androgen-secreting tumor.

Question 19

If virilization is observed what are the first tests that should be performed?

If all normal what does this exclude?

Answer 19

1. LABORATORY: DHEAS level, serum levels of TSH, prolactin, total testosterone, and follicular-phase 17-hydroxyprogesterone

EXCLUDES: adrenal tumors, hypothyroidism, hyperprolactinemia, and ovarian tumor. Common forms of late-onset congenital adrenal hyperplasia, often mistaken for PCOS, can be excluded with a normal 17-hydroxyprogesterone level.

2. IMAGING: Pelvic US and Adrenal CT

EXCLUDES: exclude an ovarian or adrenal neoplasm if the serum total testosterone level is greater than 200 ng/dL (6.9 nmol/L).

Question 20

Diagnostic criteria for PCOS?

Answer 20

(1) oligo-ovulation or anovulation, (2) clinical or biochemical evidence of hyperandrogenism (such as hirsutism or acne), or (3) ultrasound findings of polycystic ovarian morphology in at least one ovary.

Question 21

What comorbidities is PCOS associated with?

Answer 21

Polycystic ovary syndrome has a prevalence of 7% to 10% and is one of the most common endocrine disorders in young women; it is often associated with insulin resistance, metabolic syndrome, obesity and type 2 diabetes mellitus.

Question 22

Treatment for PCOS?

Answer 22

Spironolactone–teratogenic!
Dipilatory cream
Assess for high cholesterol, fatty liver, sleep apnea and diabetes

Question 23

What is the hormonal pattern for female anabolic steroid abuse?

Answer 23

Anabolic steroids may be abused by some women to enhance their athletic performance or physique. Such exogenous administration may result in absence of GnRH pulsatility and resultant hypogonadotropic hypogonadism and amenorrhea. Adverse effects may include hirsutism, acne, deepening of the voice, decreased breast size, and clitoromegaly. Withdrawal of exogenous androgens does not result in severe hypogonadism as it does in men, and most women return to regular menstrual cycles.

Question 24

What is the definition of female infertility? At what time point should an investigation begin?

Answer 24

Infertility is defined as the absence of conception after 1 year of unprotected intercourse (on average twice weekly) in a woman younger than 35 years of age.

Investigation should begin after 6 months if no conception has occurred in a woman 35 years of age or older.

Question 25

In a fertility workup, if oligomenorrhea is reported, how do you begin working up?

Answer 25

If a report of oligomenorrhea is elicited, measurement of serum TSH and prolactin levels is appropriate to exclude thyroid disease and hyperprolactinemia as causes of oligo-ovulation.

Question 26

What is the infertility workup?

Answer 26

1. Lab: TSH, prolactin
2. semen analysis
3. confirmation of ovulation with midluteal progesterone level
4. hysterosalpingogram to assess for Fallopian tube obstruction (maybe from PID?)
5. Laparoscopy for possible adhesions

Question 27

If no abnormalities are found on infertility workup, then what?

Answer 27

If no abnormalities are found… treatment to enhance endogenous gonadotropin release and increase the numbers of oocytes ovulated monthly may be warranted.

Some studies support moving directly to in vitro fertilization treatment for women with infertility at age 40 years.

In women treated with ovarian stimulation, oral medications such as clomiphene citrate or letrozole are typically used. This therapy is not appropriate in patients with POI. Patients should be counseled about the 5% to 8% risk of multiple gestation with these therapies. Referral to a reproductive endocrinologist is recommended.

Question 28

For infertility, who should not be treated with ovarian stimulation?

Answer 28

In women treated with ovarian stimulation, oral medications such as clomiphene citrate or letrozole are typically used. This therapy is not appropriate in patients with POI. Patients should be counseled about the 5% to 8% risk of multiple gestation with these therapies. Referral to a reproductive endocrinologist is recommended.