Amenorrhea

Question 1

amenorrhea - definition & key concepts

Answer 1

*absence of menstrual bleeding in a reproductive-aged woman
*amenorrhea is normal in prepubertal, pregnant, and postmenopausal females
*always start by considering pregnancy

Question 2

oligomenorrhea - defined

Answer 2

*infrequent menstrual cycles, more than 35 days apart
*moving away from this definition in favor of “abnormal uterine bleeding”

Question 3

primary amenorrhea - defined

Answer 3

*failure of menses to occur by age 16

*this terminology is different from other primary vs secondary things
*in this case, primary = you **never had a menstrual cycle)

Question 4

secondary amenorrhea - defined

Answer 4

*cessation of menses for > 3 months, sometime after menarche has occurred
*in a person who has had previously regular cycles
*pregnancy is top dx on differential

Question 5

causes of primary amenorrhea

Answer 5

1. anatomical issues:
   -imperforate hymen
   -mullerian agenesis
2. androgen insensitivity syndrome

3 other: Kallman syndrome, Turner syndrome, classical congenital adrenal hyperplasia

Question 6

causes of secondary amenorrhea

Answer 6

1. PREGNANCY
2. functional hypothalamic amenorrhea
3. polycystic ovarian syndrome
4. primary ovarian insufficiency
5. intrauterine adhesions/Asherman syndrome
6. obesity
7. other: hyperprolactinemia, Cushing syndrome, adrenal insufficiency, thyroid disease, nonclassical congenital adrenal hyperplasia

Question 7

imperforate hymen

Answer 7

*an anatomical cause of primary amenorrhea
*incomplete degeneration of the central portion of the hymen → no opening for shed uterine lining to leave
*accumulation of vaginal mucus at birth → self-resolve bulge in introitus (vaginal opening)
*untreated → cyclical abdominal pain, hematocolpos (accumulation of menstrual blood in vagina → bulging and bluish hymenal membrane)
*treatment = hymenectomy

Question 8

anatomical causes of primary amenorrhea

Answer 8

*Mullerian agenesis (failure to form Mullerian structures: uterus, etc)
*cervical stenosis
*transverse vaginal septum
*imperforate hymen
*labial fusion-agglutination

Question 9

testing for anatomical causes of amenorrhea

Answer 9

*giving a progestin challenge (a course of progestin for 10 days)
*progestin withdrawal should induce bleeding within intact structures (normal)
*if no bleeding, probably an anatomical cause of amenorrhea

Question 10

androgen insensitivity syndrome - overview

Answer 10

*genetics: 46, XY
*pathophysiology: resistance to testosterone due to a loss-of-function mutation in the androgen receptor gene
*gonad: testicle
*gonadal products: testosterone & anti-mullerian hormone

Question 11

androgen insensitivity syndrome - clinical presentation

Answer 11

*no androgen effect, minimal male patterned hair growth (testosterone does not work)
*feminized/female secondary sex characteristics present (the resultant estrogen from testosterone conversion via aromatase works fine)
*no Mullerian structures (AMH works), short vaginal opening, no cervix, no uterus

Question 12

androgen insensitivity syndrome - diagnosis

Answer 12

*pelvic exam: short or absent vagina, no uterus
*confirm absent uterus with imaging (MRI, ultrasound)

Question 13

androgen insensitivity syndrome - treatment

Answer 13

*counseling/psychological support
*surgical removal of gonads (minimize risk of cancer)

Question 14

difference in clinical presentations of androgen insensitivity syndrome vs. Mullerian agenesis

Answer 14

*BOTH will present as healthy, feminized women with short vaginal openings, no uterus, and no cervix; difference is dependent on presence/absence of pubic & axillary hair

*androgen insensitivity syndrome: no pubic hair or axillary hair
*Mullerian agenesis: pubic and axillary hair present

Question 15

Mullerian agenesis - overview

Answer 15

*genetics: 46, XX
*pathophysiology: **spontaneous degeneration or absence of the paramesonephric (Mullerian) duct [responsible for development of upper vagina, uterus, fallopian tubes]
*gonad: ovaries
*gonadal products: estrogen/progesterone and testosterone

Question 16

Mullerian agenesis - clinical presentation

Answer 16

*normal ovaries, so produce estrogen
*feminized/female secondary sex characteristics present
*shortened vagina and absence uterus
*testosterone receptors function normally → androgen effect → pubic hair growth

Question 17

intrauterine adhesions / Asherman syndrome - overview

Answer 17

*only structural cause of secondary amenorrhea
*pathophysiology: trauma to the endometrium results in formation of adhesive bands on healing that can distort or obliterate the uterine cavity
*causes include multiple procedures, biopsies, or D&C’s

Question 18

intrauterine adhesions / Asherman syndrome - clinical presentation

Answer 18

*secondary amenorrhea
*infertility
*pregnancy loss
*pelvic pain
*estrogen, progesterone, and other reproductive hormones unaffected

Question 19

intrauterine adhesions / Asherman syndrome - treatment

Answer 19

*estrogen (promote regrowth of endometrium)
*surgery to remove adhesions

Question 20

functional hypothalamic amenorrhea - overview

Answer 20

*severe caloric restriction, increased energy expenditure, decreased leptin levels, and/or stress leads to functional disruption of pulsatile GnRH release → decreased LH, FSH, and estrogen
*note: serum FSH levels may be normal; clinical history is important; consider progestin withdrawal test to evaluate for presence of endometrium

Question 21

functional hypothalamic amenorrhea - associations & treatment

Answer 21

*associated with restrictive eating patterns, eating disorders, high achievers/perfectionists, and the female athlete triad
*female athlete triad = disordered eating/excessive exercise, decreased bone mineral density, and amenorrhea
*REVERSIBLE - increase caloric intake, decrease exercise duration / intensity

Question 22

primary ovarian insufficiency - overview

Answer 22

*premature atresia of ovarian follicles in females before the age of 40
*most commonly idiopathic; can be associated with chromosomal abnormalities (Turner syndrome, fragile X), autoimmunity, chemotherapy

Question 23

primary ovarian insufficiency - clinical presentation

Answer 23

*atrophic vaginal mucosa
*hot flashes
*amenorrhea or oligomenorrhea
*may still have random ovulation (small but present change of conception)

Question 24

primary ovarian insufficiency - diagnosis and treatment

Answer 24

*low estrogen, high LH, high FSH (same as in menopause)
*treatment: estrogen (+/- progesterone)

Question 25

polycystic ovarian syndrome (PCOS) - overview

Answer 25

most common hormonal disorder among reproductive-aged women
**excessive androgen production due to high levels of LH from the pituitary gland and excessive insulin (mimics IGF-1 to increase androgen production by ovarian theca cells)

Question 26

polycystic ovarian syndrome (PCOS) - diagnosis

Answer 26

*must be 2 out of 3 Rotterdam criteria:
1. oligomenorrhea or amenorrhea
2. clinical +/- biochemical hyperandrogenism
3. polycystic ovaries

*note - diagnosis of exclusion: must exclude hyperprolactinemia, non-classical congenital adrenal hyperplasia, thyroid disease, cortisol excess

Question 27

polycystic ovarian syndrome (PCOS) - clinical features

Answer 27

*hyperandrogenism: Hirsutism (male pattern terminal hair growth), acne
*metabolic syndrome: HTN, obesity, insulin resistance (acanthosis nigricans)
*obesity
*increased risk of endometrial cancer

Question 28

polycystic ovarian syndrome (PCOS) - approach to treatment

Answer 28

*healthy lifestyle is the cornerstone of therapy
*infertility tx
*hirsutism tx: OCPs with estrogen, spironolactone
*breakthrough bleeding & irregular / absent menses tx: OCPs
*metformin in cases of hyperglycemia