Endo Reproductive Disorders

Endo Reproductive Disorders

Female Reproductive Hormone Disorders

Polycystic ovarian syndrome

• – Pathway/Axis:
  • Hypothalamic/ Pituitary/Gonads (HPG) Axis
• – Major cause:
  • increase in female production of male hormones.
  • Low estrogen levels result in incomplete development of the follicle, resulting in no ovulation and many small cysts remain on the ovary.
• – Major symptoms:
  • irregular or absent menstrual cycle, polycystic ovaries, excessive body hair, and acne.
  • Obesity can cause symptoms to worsen.

Male Reproductive Hormone Disorders

5 alpha-reductase deficiency

• – Pathway/Axis:
  • GnRH pathway
    
• – Major cause:
  • deficiency in the 5 alpha-reductase enzymes responsible for converting testosterone to DHT
    
• – Major symptoms:
  • disrupts the formation of male fetal external genitals. Genital appears to be female, not clearly male or female, or usually a small (micro) penis.

Androgen Insensitivity Syndrome

• – Pathway/Axis:
  • HPG (hypothalamus/Pituitary/Gonad)
• – Major cause:
  • Partial or complete inability of cells to respond to androgen hormones due to a mutation in the androgen receptor gene located on the X chromosome.
  • Not all AR mutations result in androgen insensitivity, this only occurs when other genetic factors are present.
• – Major symptoms:
  • Genotypic makes presenting as phenotypic females, involving decreased masculinization of male genetalia, short vagina (if female), spermatogenic defects, regression of Mullerian structures, impaired conversion of testosterone to dihydrotestosterone.
  • Symptoms range from pseudohermaphroditism to normal male phenotype but infertility.

Androgenic Alopecia

• – Pathway/Axis:
  • androgens (testosterone, DHT)
• – Major cause:
  • Type II a-reductase activity at hair follicle coverts testosterone to DHT.
  • DHT binds to DHT receptors in the scalp and leads to decreased hair growth.
  • Increased activity of DHT receptors in the scalp leads to hair follicles to be more sensitive to DHT.
  • It can also be caused by hyperactive Type II 5 a-reductase. Decreased levels of sex hormone-binding globulin can also lead to more free testosterone available to be converted to DHT.
• – Major symptoms:
  • In men- the gradual recession of frontal hairline, overtime, hairline recedes to form characteristic “M” shape, hair thins at the crown and often progresses to partial or complete baldness.
  • In women- hair becomes thinner all overhead, hairline does not recede

Aromatase deficiency

• – Pathway/Axis:
  • HPG Axis/ Androgen steroidogenesis
• – Major cause:
  • Loss-of-function mutation of the CYP19A1 gene encoding the aromatase enzyme causes a patient to lose the ability to convert androgens to estrogens in the estrogen steroidogenesis pathway.
  • Autosomal recessive inheritance.
• – Major symptoms:
  • In females, patients are born with ambiguous external genitalia and rapidly develop ovarian cysts that prevent ovulation.
  • They also do not develop secondary sex characteristics in puberty.
  • All aromatase deficient patients suffer from hyperglycemia as well as abnormal bone growth causing bones to be long, thin, and osteoporotic due to slowed mineralization.

Kallman syndrome

• – Pathway/Axis:
  • Hypothalamic/Pituitary/Gonads (HPG) Axis
• – Major cause:
  • a form of HH, a condition affecting the production of hormones that direct sexual development.
  • Isolated deficiency of GnRH
• – Major symptoms:
  • May not experience puberty or may experience incomplete puberty and symptoms of hypogonadism.
  • Men – decreased libido, erectile dysfunction, decreased muscle strength, and lack of aggressiveness and drive.
  • Women – dyspareunia and amenorrhea.
  • All patients have anosmia. fatigue, color blindness, hearing deficiency, and epilepsy. 

Klinefelter syndrome

• – Pathway/Axis:
  • testosterone (HPG) axis
• – Major cause:
  • random genetic error, most commonly nondisjunction of sex chromosomes during meiotic divisions, that result in a male being born with an extra copy of the x chromosome.
  • Extra X chromosome leads to abnormal development of the testis which results in underproduction of testosterone and elevated levels of FSH.
• – Major symptoms:
  • low testosterone (hypogonadism), enlarged breasts, small penis, weak bones, taller stature, and reduced muscle mass, facial hair, and body hair.
  • Infertility/sterility- little or no sperm production.

Primary Hypogonadism

• Management:
  • Testosterone replacement: monitor @ 1 week to levels of 400 – 700 + routine CBC and PSA

Testicular feminizing syndrome

• – Pathway/Axis:
  • Testosterone (gonads-HPG axis)
• – Major cause:
  • mutations in androgen receptors due to abnormal androgen receptor gene
• – Major symptoms:
  • XY chromosomal male with female external genitalia (complete androgen insensitivity) or micropenis, gynecomastia, hypospadias (incomplete androgen insensitivity) but no ovaries, fallopian tubes, or uterus (testes are present in the abdomen); normal production of testosterone and conversion to dihydrotestosterone. No menstruation during puberty.

Hermaphrodites

True hermaphroditism

• – Pathway/Axis:
  • HPG axis
• – Major cause:
  • an individual has both testicular and ovarian tissue.
  • This can be caused by either SRY gene being expressed in one gonad but not the other or partial expression in the gonads during development
• – Major symptoms:
  • ambiguous genitalia at birth, delayed or unexpected puberty, enlarged clitoris or micropenis, fused labia, or urethra opening is not in the correct position.