Reproductive Endocrinology

Question 1

CAH (Epi, Path)

Answer 1

Epi: AR, 90% 2/2 21-hydroxylace (CYP 21) Deficiency

Classical: Failure of cortisol production > elevated ACTH > virilization

• Salt-wasting (3/4)
• Simple virilizing

Nonclassical:

Question 2

CAH (Dx, Tx)

Answer 2

Dx: CVS, analyze CYP21 and 11b-hydroxylase genes

Tx: Dexamethasone)

• Prenatal treatment (masculinization of genitalia begins at 6-7 weeks, ~8-9 wks after LMP)
• Cx: Rare FTT, Psychosocial delay; maternal wt gain, edema, HTN< abnl GTT< cushingoid.

Nonclassical: No treatment required, benefit from genetic counseling

Question 3

Labial Adhesions

Answer 3

• Aka labial agglutination/labial fusion/vulvar synechia
• upt o 1.8% of girls

Asx vs infl/dysuria/UTI/obstxn

Dx: Screen for UTI

• 80% resolve spontaneously in 1y, percistence p puberty rare
• screen for abuse

Tx:

1. • Estrogen cream x weeks

Question 4

Emergency Contraception

Answer 4

1 Levonorgestrel (1.1% pregnancy)

• 1 dose regimen 1.5mg x1
• 2 dose regimen, 0.75mg Q12h x2

Combo OCs (3.2%) - more nausea)

• 100mcg EE / 0.5 levo Q12h x2 + antiemetic 1h after first dose

Paragard

Up to 120h after

Question 5

Donor oocyte use

Answer 5

Elevated Day 3 FSH >10-15) diminished pregnancy potential

Question 6

11 Beta-hydroxylase deficiency

Answer 6

<5% of CAH; 1:100,000 live births

Cannot convert corticosterone to aldosterone; cannot convert 11-deoxycortisol to cortisol (XCS CRH and adrenal hyperplasia_

Dx:

• Elevated 11-deoxsycorticosterone, 11-deoxycortisol, androgens, total urinary 17-ketosteroids

HTN, Na/water retention, volume expansion, hypokalemia

Question 7

Other Enzymatic Deficiencies

Answer 7

1. 3B hydroxysteroid dehyrdogenase deficiency
   - adrenal insufficiency, mild virilization; late onset hirsutism and menstrual irregularities
2. 17alfpha hydroxylase deficiency
   - cortisol and sex steroid deficiency
   - HTN, sexual infantilism, pseudohermaphroditims

Question 8

Steroid Synthesis Pathway

Answer 8

Question 9

Antiresorptives in Reproductive Age Women

Answer 9

ESTROGENS

SERMS

Vit D

Calcium

Calcitonin

Bisphosphonates (not recommended, can affect fetus)

Question 10

Swyer Syndrome

Answer 10

46, XY gonadal dysgenesis

• Female external genitalia, uterus, fallopian tubes (vs complete androgen insensitivity

Question 11

Gonadal Dysgenesis

Answer 11

Persons who have streak gonads rather than ovaries

(Monosomy X vs Swyer syndrome 46, XY)

Question 14

5-alpha reductase deficiency

Answer 14

AR, 46, XY

Impaired conversion of T > DHT

Bilateral testes with impaired virilization during embryogenesis (DHT eneded for testicular descent)

Testes present > MIF produced, mullerian structures not maintained

Px: female child masculinizes during puberty, poor breast development

40fold increased testicular cancer risk

Question 15

How Frequently do Pregnant women with Bicornuate Uterus have a term live delivery

Answer 15

60%

Question 16

Delayed Puberty Definitions

Answer 16

Workup when

• No secondary sex characteristics by age 13
• Absence of menarche by 15
• 5 years between onset of thelarche and menarch

Question 17

Delayed Puberty Etiologies

Answer 17

Hypergonadotropic Hypogonadism (Ovarian Failure)

• Ovarian Failure
  
  • Turner’s, 46,XX, 46XY (Swyer’s syndrome vs androgen insensitivity)
• Other Rare
  
  • 17a-hydroxylase deficiency
  • Resistant Ovary Syndrome

Hypogonadotropic Hypogonadism (CNS, pituitary)

• Reversible
  
  • Physiologic
  • Wt loss/anorexia
  • Prolactinoma
  • Primary hypothyroidism
  • CAH
  • Cushings
• Irreversible
  
  • GnRH Deficiency
    
    • Kallmans
    • Prader Willi
    • GP54R (Leptin-R deficiency)
    • Radz
    • infiltrative dz
  • Hypopituitarism
  • Craniopharyngioma
  • Congenital CNS defect
  • Pituitary Adenoma
  • Malignant pituitary tumor

Question 18

Amenorrhea and Blind Pouch

Answer 18

• MRKH
  
  • Nl pubic hair/breasts, no cyclic pain
  • 20-25% w renal anomalies, 15%s skeletal
• AIS
  
  • Scant pubic hair, nl breast, no pain
  • Androgen receptor defect
  • Unopposed E > Breasts
  • Have tests
  • AMH present so > no uterus
• Transverse Septum
  
  • Nl pubic hair/breasts. Cyclic Pain

Question 19

Primary Amenorrhea and Elevated FSH

Answer 19

• Gonadal Failure
• XO or mosaic
• Galactosemia (FTT, abnl FSH/LH, failure of germ cellmigration to ovary)
• 17a-hydroxylase deficiency (HTN, hypokalemia, high 17-OHP)

Question 20

Turner’s Syndrome (Evaluation and Tx)`

Answer 20

• IVP/renal US, ECHO, hearing exam, TSH/free T4, fasting glucose
• Tx: Growth hormone and estrogen treatment later

Question 21

Steroid Synthesis

Answer 21

• Starts with Choleesterol
• Rate limiting rxn: Side chaing cleavage to 21C pregnenolon
• 21 Carbons: Progestins, glucocorticoids, mineralocorticoids
• 19 carbons: Androgen
• 18 C: Estrogens

Question 22

Adrenal Steroid Disorders

Answer 22

• CAH
  
  • 21 hydroxylase deficiency (90% cases)
  • 11b hydroxylase deficiency (5% cases)
  • 3beta hehydrogenase deficiency (rare)
• Pubertal Disorders vs Ambiguous Genitalia
  
  • 17 alpha hydroxylase deficiency
  • 17 beta dehydrogenase deficiency

Question 23

17alpha hydroxylase deficiency

Answer 23

• Presentation
  
  • Male Ambiguous Genitalia
  • Female pubertal delay
  • HTN 2/2 mineralocorticoid effect of 11-DOC
  • NA retension, water expansion, hypokalemia
  • low urinary 17-ketosteroids