207. Endo Control, Female Repro II

Question 1

Define oligomenorrhea
Define amenorrhea (primary vs secondary)

What does the presence of breast development tell you?

Most common cause of amenorrhea

Answer 1

Oligomenorrhea: infrequent menses
Amenorrhea: absense of menses
Primary: no menarche
Secondary: abnormal cessation of menses (>6mo)

breast development: NO = no E production (eval for delayed puberty)
yes = E production = assess anatomy before endo workup

Most common cause of amenorrhea: PREGNANCY, contraception can fail!

Question 2

What is an endocrine disorder causing amenorrhea?

• sx
• causes
• tx

Answer 2

HyperPRL: normal - lactational amenorrhea (suppress GnRH while breastfeeding to avoid another pregnancy)
Sx: galactorrhea, infertility, menstrual disturbance, hypogonadism (low E = hot flashes, vaginal dryness, osteoporosis)
Causes: Drugs decreasing DA (anti-psychotics, anti-depressants, anti-HTNs, opiates), prolactinoma, “empty sella” syndrome disrupting DA delivery, hypothyroidism (high TRH = high PRL)
tx: DA agonists (bromocriptine, cabergoline)

Question 3

How to assess Anatomy and Outflow Tract?

What 3 tests do you do, and what do the results show you?

Answer 3

Puberty? If no = imaging

P Challenge (does pt bleed 2-7 days after P?)

• positive withdrawal bleed = normal anatomy w/ intact outflow tract, but implies anovulation w/ normal E production (uterine lining stuck in proliferative phase)
• negative withdrawal bleed = either abnormal anatomy or no E production

E-P Challenge (prime endometrium with E for 21 days, then induce P withdrawal bleed) - only when negative P challenge

• positive E-P withdrawal bleed: normal anatomy, low E
• • use FSH to further delineate ovarian function
• negative E-P withdrawal bleed: abnormal anatomy

Question 4

What disease state is assoc with normal puberty, and positive withdrawal bleed to P challenge?

• what is it
• sx
• dx
• labs
• assoc
• pathophys
• tx

Answer 4

PCOS: excess androgen from ovary = no dominant follicle selected = no ovary
sx: amenorrhea, hirsutism, obesity
Dx: exclude other causes hyperandrogenism, 2/3 of oligo +/- anovulation, hyperandrogenism, US with >12 follicles in each ovary or large ovarian volume
Labs: T elevated (but not highly in tumor state), DHEAS not elevated (adrenal path), 17-hydroxyprogesterone not elevated (CAH), 24hr urinary free cortisol not elevated (Cushing Syndrome), r/o tumor
Assoc:
- ins resistance: assoc with impaired glu tolerance and high fasting glu; ins increases androgen production from ovary
- obesity: causes increased ins resistance = increased ins = increased ovarian androgens
- persistant anovulation: loss of hormonal cycling, E normal due to small follicule E production, and high aromatase in fat

PPhys: high LH:FSH ratio - theca cells LH-R produces androgens to GCs; GCs FSH-R produce aromatase to make E; High LH-FSH ratio = androgen overproduction

High risk endometrial cancer due to E without P = uterine growth

Tx: OCPs (decrease FSH/LH = decreased ovarian androgens; high E increases SHBG which decreases free T; helps reduce acne, hirsutism, cycle control, endometrial hyperplasia)

Question 5

What disease state is associated with puberty, negative P withdrawal bleed, Positive E-P withdrawal bleed, High FSH

• what is it
• different etiologies
• tx

Answer 5

Ovarian Failure

1. MP: 1 year after final menses, dx high FSH but low E/inhibin (no follicles), abnormal is <40yo
2. Gonadal dysgenesis: early ovarian failure, streak gonads (accelerated atresia, gonad replaced by fibrous tissue, sx (lack of puberty, primary amenorrhea - MOST COMMON CAUSE 45%, premature ovarian failure due to high FSH/LH with low E), caused by TURNER SYNDROME (45XO, lack of pubery, webbed neck, wide carrying angle, broad chest)
3. Fragile X Pre-mutation carrier: 12-28% have menopause <40yo, carry gene for mental retardation in males
4. Polyglandular Autoimmune Disease: auto-antibodies to endo organs - disrupt ovulation (oocytes present, but ovulation uninducible)

Tx: HRT: induce puberty, relieve low E sx and maintain BMD until mp age
Fertility requires oocyte donation

Question 6

What disease state is associated with normal puberty, negative P-challenge withdrawal bleed, positive E-P withdrawal bleed, low/normal FSH?

• what is it
• causes
• tx

Answer 6

Hypothalamic Central Failure - does not respond to low E levels (Low normal FSH/LH with low E)

cause:
1. Disorders of GnRH decifiency/resistance: genetic defects = lack of puberty (Kallman’s syndrome); Destructive lesions to pit
2. Aberrant GnRH secretion: poor nutrition, physical stress, emotional stress (use LH to indirectly measure GnRH not systemic, will also have high cortisol due to high stress - not abnormally high); Frisch’s Critical Weight Hypothesis: fatness to determine menstrual cycle maintenance/onset (17% body fat at menarche, 22% body fat for menstrual cycle); LEPTIN restores normal hormone levels, Kisspeptin stim GnRH release to induce puberty

Tx: HRT (tx hypoE sx, maintain BMD); Fertility (injectable FSH/LH, GnRH), Behavioral tx (decrease perfectionism, improve diet)

Question 7

What two diseases are assoc with normal puberty, negative P Challenge withdrawal bleed, negative E-P withdrawal bleed?

Answer 7

Abnormal Anatomy

1. Asherman’s Syndrome: intrauterine scarring (synechiae) due to D&C assoc w/ infection/pregnancy, prior uterine surgery
2. Cervical Stenosis: hx of cone biopsy
3. Congenital: Urogenital anomalies, absense of mullerian structures (androgen insensitivity, mullerian agenesis)