Uterine cycle

Formation of Corpus luteum

1. After ovulation, ruptured follicle collapses → antrum fills with clotted blood → corpus hemorrhagicum

2. Remaining granulosa + theca cells enlarge, fill with yellow lipid → corpus luteum (“yellow body)

3. Capillaries invade→ richly vascularized (provides cholesterol for steroidogenesis)

endocrine output of corpus luteum

• Progesterone: Dominant hormone; prepares endometrium for implantation; thickens cervical mucus; inhibits uterine contractions

• Estrogen: contributes to negative feedback on FSH/LH

• Inhibin: contributes negative feedback on FSH (prevents new follicle development

lifespan and fate of corpus luteum

• During non-pregnancy:

  • Without continued LH (suppressed by progesterone/estrogen negative feedback),

  • CL degenerates → corpus albicans (white scar).

  • Progesterone + estrogen fall → releases negative feedback → FSH rises → new cycle begins

  • Lasts 12 days

• During pregnancy:

  • Embryo produces hCG (human chorionic gonadotropin) →

  • rescues corpus luteum →

  • maintains progesterone production until placenta takes over ( 3 months)

What do prenancy tests detect

hCG in blood and urine

3 phases of uterine(menstrual) cycle

Driven by ovarian hormones acting on the endometrium

1. Menstrual phase

2. Proliferative phase

3. Secretory phase

The uterine cycle is entirely dependent on the ovarian cycle. Remove the ovaries → uterine cycle stops. The endometrium is a hormone-responsive tissue that faithfully reflects what the ovary is doing

Menstrual phase

• Occurs on days 1-5 of the 28 day cycle

• corresponds to early follicular (ovarian)

• Dominant hormone is estrogen

  • progesterone is at lowest

Processes of menstrual phase

• triggered by progesterone withdrawal

  • Progesterone relaxes myometrium. Its loss leads to contraction

• spiral arteries spasm → ischemia(blood flow is cut off) → functionalis dies and detaches

  • Spiral arteries depend on progesterone to maintain vasodilation

• “Menstruation is a vascular event first

• Functional layer detaches and is shed (menstrual flow= blood + tissue)

• Basalis survives (supplied by straight arteries — unaffected by hormonal withdrawal)

• Meanwhile: rising FSH begins new follicle recruitment in the ovary

Proliferative phase

• Occurs on days 6-14 days of 28 day cycle

• Corresponds to follicular (ovarian)

• Dominant hormone is estrogen

• Consists of functionalis rebuilding from basalis→ glands enlarge; spiral arteries regrow; endometrium thickens 1-6 mm

Process of Proliferative phase

• Rising estrogen from growing follicles drives regeneration from basalis stem cells

• Estrogen also upregulates progesterone receptors in endometrium → primes tissue to respond to progesterone in the secretory phase

• Cervical mucus thins → forms channels that facilitate sperm passage

• Ends with ovulation (day 14)

Secretory phase

• Occurs on days 15-28 days of the 28-day cycle

• Corresponds to luteal phase

• Dominant hormone is progesterone

• functionalis becomes secretory mucosa→ glands coil and secrete glycogen + nutrients→ spiral arteries elaborate

Processes of secretory phase

• Progesterone (from corpus luteum) converts endometrium into secretory mucosa

• Endometrial glands actively secrete glycogen + nutrients into uterine cavity (preparing to feed a potential embryo)

• Cervical mucus thickens → re-forms cervical plug (blocks sperm + pathogens)

• Implantation window: uterus maximally receptive days 20-22 ( 6-7 days after ovulation)

• If no fertilization: CL degenerates ( day 24) → hormones drop → ischemic phase (last 2-3 days) → menstruation

Anchor figure

Four panels, aligned by day, showing how everything connects:

• Panel (a): Gonadotropin levels (FSH + LH) — the pituitary signals

• Panel (b): Ovarian cycle (follicle → ovulation → corpus luteum) — the

events

• Panel (c): Ovarian hormones (estrogen + progesterone) — the output

• Panel (d): Uterine cycle (menstrual → proliferative → secretory) — the

response

• Read top to bottom at any day: what's the pituitary doing? → what's the

ovary doing? → what hormones are out? → what's the uterus doing?

Big coordination

Day by day intergration

How does uterine cycle depend entirely on ovary

Remove the ovaries → uterine cycle stops

• The endometrium is a hormone-responsive tissue that faithfully reflects what the ovary is doing

• Estrogen builds. Progesterone stabilizes. Without both, the functionalis is shed.

• If pregnancy: embryo produces hCG → rescues CL → progesterone maintained → no menstruation

• If no pregnancy: CL dies → progesterone falls → spiral arteries spasm → menstruation → cycle restarts

What happens if pregnancy occurs during uterine cycle

• Embryo produces hCG → rescues corpus luteum →

• progesterone maintained →

• endometrium maintained →

• no menstruation. hCG is detectable in urine/blood = basis of pregnancy tests.

Hormonal regulation at puberty

• Same initial event as males: hypothalamus becomes less sensitive to low levels of gonadal hormones → GnRH rises → FSH + LH rise

• In females, onset is linked to adipose tissue and its secretion of leptin

A woman takes combined oral contraceptive pills containing estrogen + progesterone continuously. Why does this prevent ovulation?

Continuous estrogen + progesterone → negative feedback on FSH/LH

• → no FSH rise → no follicle recruitment

• → no dominant follicle → no estrogen threshold

• → no positive feedback → no LH surge → no ovulation

• Primary mechanism: ovulation suppression

• Secondary: thickened cervical mucus + thinned endometrium

Estrogen

• Reproductive: promotes oogenesis + follicle growth; drives proliferative phase

• Secondary sex characteristics (puberty):

  • Breast development

  • fat redistribution (hips, breasts)

  • widening of pelvis

• Growth: rapid growth spurt (ages 11-12) → epiphyseal plate closure (full height by 13-15)

• Metabolic: maintains low total cholesterol / high HDL → cardiovascular protection

• Skeletal: facilitates calcium uptake → bone density maintenance

Progesterone

‘prgenancy hormone’

Uterine: drives secretory phase; quiets myometrium (inhibits contractions — critical in pregnancy)

• Cervical: thickens cervical mucus → forms cervical plug

• Breast: promotes breast development for lactation (with estrogen)

• Metabolic: promotes diuresis; raises basal body temperature

• Clinical use: basal body temperature ↑ confirms ovulation (progesterone from CL)

• Works alongside estrogen — estrogen builds, progesterone stabilizes and

maintains

Puberty in females

Same initial event as males:

• Hypothalamus becomes less sensitive to low gonadal hormones → GnRH rises → FSH + LH rise

• In females, onset linked to adipose tissue and leptin

• Leptin: adipose-derived hormone that informs hypothalamus energy stores are sufficient for pregnancy

• FSH → estrogen from granulosa cells (via two-cell model)

• Estrogen drives puberty over ~4 years

Leptin-fat connection

Estrogen-driven puberty

• lasts 4 years

• Growth and maturation of breasts + reproductive organs

• Fat redistribution (hips, breasts)

• Bone maturation: growth spurt → epiphyseal plate closure (earlier than males → full height by ages 13-15)

• Cycles initially anovulatory → first menstruation = menarche

• First ovulatory cycle may not occur until months after menarche

FSH-Driven process

FSH stimulates estrogen secretion by granulosa cells (LH provides androgen precursor from theca cells — two-cell model callback

Exercise-induced Amenorrhea

• Extreme exercise or eating disorders → low body fat → low leptin → insufficient GnRH stimulus → low FSH/LH → inadequate follicle development → anovulation → amenorrhea (loss of menses).

• Result: Loss of estrogen → bone loss (estrogen protects bone density) → osteoporosis-like changes in young women.

An athlete with very low body fat stops menstruating.

Explain the mechanism — trace it from adipose tissue to the uterus.

Menopause

cessation of menses for ≥ 12 consecutive months. Mean age:  51.4 years in North America.

Diagnosed retrospectively

Primary cause of menopause

Depletion of ovarian follicles

— after decades of monthly recruitment + atresia, the follicle supply is exhausted

→ ovary can no longer produce significant estrogen or progesterone.

Hormonal consequence of menopause

• Without ovarian estrogen/progesterone → no negative feedback → FSH and LH levels rise dramatically

• But no follicles remain to respond → elevated gonadotropins are a hallmark lab finding of menopause

Perimenopause

• Transitional years extending from early 40s onward

• Ovarian function wanes → cycles become irregular

• Estrogen deprivation symptoms begin: hot flushes, insomnia, irritability, fatigue, headaches, mood changes, loss of libido

Post-menopausal effects on genital tissues

• Atrophy, vaginal dryness, increased infections

• Caused by loss of estrogen trophic support

Post-menopausal effects on Urinary tract

• Frequency, urgency, incontinence

• Caused by bladder + urethral linings have estrogen receptors

Post-menopausal effects on Breasts

• Some atrophy

• caused by loss of estrogen stimulation

Post-menopausal effects on Cardiovascular

• Increased atherosclerosis + stroke risk

• Caused by loss of estrogen’s cardiovascular protection (low cholesterol/high HDL effect)

Post-menopausal effects on Skeleton system

• Leads to osteoporosis (accelerated bone resorption)

• Caused by loss of estrogen’s bone-protective effect

Hot flushes

Hot flushes are caused by estrogen withdrawal (the change in levels, not the absolute level). Fluctuating estrogen levels disrupt the hypothalamic thermoregulatory center

Female sexual response

• PNS-driven arousal: clitoral and vestibular bulb engorgement (erectile tissues homologous to male corpus cavernosum and corpus spongiosum)

• Vaginal lubrication from interstitial fluid transudation across vaginal epithelium + cervical mucous glands

• No refractory period (unlike males)

• Orgasm not required for conception — oocyte capture and sperm transport occur independently of orgasm