Reproductive Endocrine Disorders

BCH 130 — Advanced Human Biochemistry · Dr. Radi

build Jul 18 · 08:35 · CC BY-NC-SA 4.0 · owned figures (RDKit / matplotlib)
Dr. Radi

By the end of this unit, you can…

  • Explain PCOS pathophysiology: LH-driven ovarian hyperandrogenism amplified by insulin resistance, and the Rotterdam…
  • Connect PCOS to anovulation, metabolic risk, and its management (insulin sensitizers, anti-androgens, ovulation induction).
  • Describe endometriosis as estrogen-dependent ectopic endometrial tissue with local aromatase expression and progesterone resistance.
  • Justify hormonal therapy (progestins, GnRH analogs, aromatase inhibitors) by the estrogen-dependence of the lesions.
Dr. Radi

Today's route 🗺️

  1. Polycystic Ovary Syndrome
  2. Endometriosis
  3. Sex Determination & Its Disorders
Dr. Radi

1 · Polycystic Ovary Syndrome

"PCOS is the most common endocrine disorder in women of reproductive age — and it's a beautiful crossroads of reproductive AND metabolic biochemistry. Let's build it from the molecule up: too much LH, an ovary making too many androgens, and insulin resistance pouring gasoline on the fire."

Dr. Radi

Two hits pile androgens onto the ovary

Here's the engine. Rapid GnRH pulses push the pituitary to favor LH over FSH, and LH drives the theca cell to crank out androgens. Now the twist that makes PCOS metabolic: insulin resistance means insulin runs sky-high — and insulin is a co-gonadotropin, amplifying LH at the theca and dropping liver SHBG so even more androgen runs free.

Dr. Radi

Rotterdam: any two of three

How do we name it? Rotterdam criteria — any 2 of 3: hyperandrogenism (hirsutism, acne, high free testosterone), oligo-/anovulation, and polycystic ovaries on ultrasound. Those "cysts" are really antral follicles arrested mid-development — no FSH surge, so no follicle is ever chosen to ovulate.

Dr. Radi

Treat the driver, not just the symptom

PCOS is a metabolic disease, so we treat mechanisms. Insulin sensitizers (metformin) and weight loss attack the insulin driver. A combined OCP quiets LH and raises SHBG; anti-androgens block the receptor for hirsutism. For fertility, ovulation induction with letrozole restores the surge. And screen everyone for diabetes!

Dr. Radi

2 · Endometriosis

"Endometriosis is deceptively simple to state — endometrial tissue growing where it doesn't belong — and fiendishly biochemical underneath. The lesion makes its OWN estrogen and ignores the hormone that's supposed to shut it down. Get that, and every drug we use makes perfect sense."

Dr. Radi

Right tissue, wrong place

Endometriosis is functioning endometrial tissue growing outside the uterus — on the ovary, peritoneum, bowel, anywhere in the pelvis. It's still hormone-responsive, so it grows and bleeds cyclically wherever it landed. Trapped blood means inflammation, adhesions, and scarring — the source of the crushing pain and infertility. And every implant runs on one fuel: estrogen.

Dr. Radi

The lesion feeds itself estrogen

Here's what makes it relentless. The lesion expresses local aromatase — making estradiol on-site, no ovary required. That estrogen drives COX-2 → PGE2, and PGE2 induces more aromatase: a vicious feed-forward loop. Worse, the lesion is progesterone-resistant (PR-B lost) — the hormone that should brake estrogen can't.

Dr. Radi

Every drug lowers estrogen

See the lesions as estrogen-dependent and therapy is obvious — starve them of estrogen. Progestins oppose estrogen and atrophy the tissue. GnRH analogs shut the ovary down — a reversible medical menopause. Aromatase inhibitors block estrogen synthesis, hitting both ovarian and that sneaky local source.

Dr. Radi

3 · Sex Determination & Its Disorders

"To understand what goes wrong, you first need the normal blueprint — and it's gorgeous biochemistry. One gene flips the switch, two hormones from the testis build the male body plan, and the default is female. Learn the three signals, and every disorder is just a broken step in that sequence."

Dr. Radi

The blueprint: SRY, AMH, and DHT

The default body plan is female. A single Y-borne gene, SRY, flips the bipotential gonad into a testis — and the testis makes two things. Sertoli cells secrete AMH, which removes the Müllerian ducts. Leydig cells make testosterone, which builds the Wolffian ducts and — after 5α-reductase converts it to DHT — the external male genitalia. No SRY, no testis: ovary, uterus, female.

Dr. Radi

When a whole chromosome is off

Start with the aneuploidies. Turner (45,X) has a single X — a streak gonad, so no estrogen and primary amenorrhea; the short stature (SHOX loss) and webbed neck (fetal lymphedema) come from the missing X itself. Klinefelter (47,XXY) has an extra X — small firm testes, low testosterone, tall stature, gynecomastia. Both are primary hypogonadism: the gonad failed, so FSH and LH climb.

Dr. Radi

When one step in the pathway breaks

Now watch the same testes and testosterone give three different bodies — depending on which step fails. Androgen insensitivity: the receptor is deaf, so a 46,XY body goes female. 5α-reductase deficiency: no DHT, so ambiguous at birth, then virilizing at puberty. CAH (21-hydroxylase): blocked cortisol shunts precursors into androgens, virilizing a 46,XX child.

Dr. Radi

Can you…?

  • ☐ explain PCOS pathophysiology: LH-driven ovarian hyperandrogenism amplified by insulin resistance, and the Rotterdam…?
  • ☐ connect PCOS to anovulation, metabolic risk, and its management (insulin sensitizers, anti-androgens, ovulation induction).?
  • ☐ describe endometriosis as estrogen-dependent ectopic endometrial tissue with local aromatase expression and progesterone resistance.?
  • ☐ justify hormonal therapy (progestins, GnRH analogs, aromatase inhibitors) by the estrogen-dependence of the lesions.?

If any box stays empty, the practice site has a drill for it. 🧪

Dr. Radi