Menstrual cycle (+ Overview)

HPG axis : What feedback does Activin, Inhibins, Progestins, Estrogens give and where (include midcycle)?

Basic remember: Hypothalamus (+) → GnRH → Anterior Pituitary (+) → FSH & LH → Ovaries (+) → Estrogen , Progestins, Inhibins, Activins

Feedbacks 

• Progesterone and estrogen - feedback on hypothalamus and anterior pituitary (gonadotropes) = ↓ GnRH , ↓ FSH , ↓ LH 

• Inhibins give - feedback gonadotropes =  ↓ FSH, ↓ LH

• Activins give + feedback on gonadotropes = = ↑ FSH, ↑ LH 

Midcycle

• Mid- cycle high estrogen give + feedback = ↑ GnRH ,  ↑ LH

• Mid cycle even progesterone give + feedback for LH but too small so negligible 

Female hormones non preg, prego, lactating ?

Non preg = Estrogen , Progestins, Activins and inhibins

Prego = hCG, Estrogen, Progesterone, hPL, Relaxin

Lactating Female = Prolactin and oxytocin

Menstrual cycle : Define menstruation, menarche and menopause and what is duration of menses , cycle length and amount ml

• Menstruation: The periodic discharge of blood, mucus and soughed endometrium at cyclic interval from menarche to menopause

• Menarche : 1st menstrual cycle / menstrual bleeding 10-16 yrs (Avg:13 yrs)

• Menopause: Permanent end of menstruation 45-55 yrs (Avg: 51 yrs)

• Duration of menses : 5 (± 2 days)

• Cycle length : 21 - 35 days (Avg : 28 days)

• Amount: 30 - 80 ml

Components of Menstrual cycle

Pre-ovulation 
Ovarian cycle --> (Menstrual and) Follicular phase 
Uterine/endometrial cycle --> Menstrual phase (period) and Proliferative phase 

Ovulation 
Ovarian cycle --> Ovulation
Uterine/endometrial cycle --> End of proliferative phase  

Post-ovulation 
Ovarian cycle --> Luteal phase 
Uterine/endometrial cycle --> Secretory phase 

Ovarian cycle (recap)

Follicular phase

• Low levels of estrogen and progesterone cause pituitary to secrete FSH

• FSH cause egg to mature into follicle (ovary)

• Follicle secrete estrogen which causes uterine lining (endometrium) to thicken

Ovulation

• Estrogen production inhibits FSH production

• Pituitary secretes LH (LH surge) causes follicle to burst and release mature egg into Fallopian tube

Luteal phase

• Burst follicle turns yellow & becomes corpus luteum which produces progesterone to maintain thick uterine lining

• LH production decreases

Menstrual phase

• If fertilisation doesn’t occur corpus luteum disintegrates

• Progesterone secretion decreases causing uterine lining to detach from uterine wall

• Tissue, egg , and blood are discharged from body

• 

Hormonal regulations at various parts of menstrual cycle 

Hormonal regulations at various parts of menstrual cycle 

1. Early–Mid Follicular Phase

• GnRH → FSH → stimulates Granulosa cells → Converts androgens into estrogen

• GnRH → LH (basal level) → stimulates theca cells → secretes androgens

Result : ↑ Estrogen , mild FSH inhibition by inhibin from granulosa cells.

Feedback: Low-moderate estrogen → - feedback on GnRH, LH,FSH

2. Late Follicular Phase & Ovulation

• High sustained estrogen → switch to + feedback on hypothalamus and pituitary

• → LH surge (6 - 10 fold increase) + small FSH rise

• LH surge → Ovulation (follicle rupture)

• Granulosa cells produce inhibin and more estrogen just before rupture

End Result: Ovulation + Formation of corpus luteum

3. Early–Mid Luteal Phase

• Corpus luteum forms → secretes ↑ progesterone, ↑ estrogen, ↑ inhibin.

• High hormones → - feedback → ↓ GnRH, ↓ FSH, ↓ LH (prevents new follicles).

• LH maintains corpus luteum function initially

4. Late Luteal Phase
   

• If no pregnancy : Corpus luteum degenerates → Estrogen, ↓ Progesterone, ↓ Inhibin → release of pituitary inhibition → ↑ FSH → new follicle growth begins and progesterone withdrawal → menstrual bleeding

• If pregnancy → hCG maintains corpus luteum → continues estrogen and progesterone secretion

Uterine cycle : Describe Phases incl Days

Menstrual phase (Day 1-5)

• Ovarian hormones at lowest levels

• Functional layer sheds due to progesterone withdrawal and vasoconstriction of spiral arteries → these 2 factors can cause transient hypoxia

Proliferative phase (Day 6-14)

• Estrogen levels rise

• Vascular & endothelial tissue proliferation

• Endometrial stromal cells (ESCs) produce VEGF (vascular endothelial growth factor)

• Endothelial cells express Angiopoietin 2 → ↑ Angiogenesis

• Glands enlarge and ↑ number of spiral arteries

• ↑ synthesis of endothelium receptors

Secretory phase (Day 15-28)

• Rising progesterone levels in granulosa. cells stimulate →

1. Endometrial stromal cells to express Angiopoetin 1

2. Growth & coiling of spiral arterioles

3. Uterine glandular secretory activity

• If no fertilisation: ↓ progesterone and ↓estradiol levels → spiral arteries kinking & spasm, gland regression, endometrium necrosis → menstruation

• Fertilisation: Secretory activity maintained

  

Events during menstrual cycle and physiological changes (incl pics)

Physiological menstrual change:
Body temp increase (due to progesterone after ovulation) , Cervical mucus 

Cervical mucus change during menstrual cycle

1. Menstruation/ Follicular = Thick mucus so passage difficult 

2. Ovulation = Water mucus so allows passage 

3. Luteal phase = Thick mucus hinder passage 

Disorders of menstrual Cycle (Define Amenhorrea (1ry & 2ry) , Menorrhagia, Hypomenorrha, Metrorrhagia , Oligomenorrhea , Dysmenorrhea)

Amenhorrea : Absence of menstrual period of female in reproductive age

• Primary : Period never occurs

• Secondary: Cycle cease after normal period

Menorrhagia : Excessive bleeding during menstruation

Hypomenorrhea: Scanty or little bleeding

Metrorrhagia : Bleeding between cycle

Oligomenorrhea : Reduced period frequency

Dysmenorrhea : Painful periods