The document summarizes the physiology of menstruation, including the hormonal interactions between the hypothalamus, pituitary gland, and ovaries that regulate the menstrual cycle. It describes the follicular phase of follicle development and selection of the dominant follicle, ovulation, and the luteal phase when the corpus luteum forms and produces progesterone. It also discusses changes in the endometrium across the menstrual cycle in response to rising and falling hormone levels.

1. Physiology OfPhysiology Of
MenstruationMenstruation
Disusun Oleh:
Nur Afiqah Binti Jasmi 11-2013-031
Luqman Hakim Bin Mohd Jais 11-2013-170
Dokter Pembimbing:
dr Harianto Wijaya Sp.OG
Kepaniteraan Klinik Ilmu Obstetri & Ginekologi RSUD Tarakan
Fakultas Kedokteran Ukrida

2. MENSTRUAL CYCLE
• Menstrual Cycle: 28 ±
7 days . Varied
• Menstrual flow:4 ± 2
days
• Hypothalamus-
Pituitary-Ovary Axis
• Hormone
Communication

4. HYPOTHALAMUS
Hypothalamus ----------------------------------------------> Circulating
Hormones
Hypothalamus ------------------------------> Pituitary
Hypothalamus ------>Hypothalamus
Long Feedback Loop
Short Feedback Loop
Ultrashort Feedback Loop

5. REPRODUCTIVE FUNCTIONS OF
THE HYPOTHALAMUS
Gonadotropin-Releasing Hormone
• Decapeptide
• From arcuate nucleus
• Half life : 2-4 minutes
• Gonadotropin-releasing hormone (GnRH) ->
controlling factor for gonadotropin secretion.
• Kiss1 gene -> Kisspeptins -> GPR54
(receptor) -> Signaling GnRH & GAP
secretion

6. Neuronal BodyNeuronal Body
Pre-pro-GnRHPre-pro-GnRH
GnRH decapeptide
GAP
GnRH decapeptide
GAP
Portal VesselPortal Vessel
ProteolyticProteolytic
Nerve terminalNerve terminal
GnRH geneGnRH gene

7. GnRH Pulsatile Secretion
Continuous Exposure
Downregulation
GnRH receptor
decrease
Intermittent Exposure
Upregulation
Autoprime
GnRH receptor
increase

9. Follicular Phase Luteal PhaseMid Follicular

10. Endogenous Opioids and Effects on
GnRH
Opioid Endorphin ↑ Inhibit
GnRH
releases
Ovarian Sex
Streoids
Endorphin
Peak: Luteal Phase
Nadir: Menses

11. PITUITARY
Gonadotrophs are
specialized cell types of
the anterior pituitary that
synthesize and secrete
LH and FSH
Gonadotrophs contain
cell-surface GnRH
receptors that mediate
the action of GnRH.

12. Gonadotropin-Releasing Hormone Receptor
• Hypothalamic GnRH -> Pituitary -> GnRH type
I receptor -> activation of Gq/11.
• PKC-, Ca2+-, and tyrosine kinase–dependent
pathways.
• Type 2 receptors: Inhuman Primates

13. Identical α subunit
Gonadotropins Location of β-subunit
gene
Size of β-subunit Half-life in serum
FSH Chromosome 117aa[*] 3-4h[†]
11p13
LH Chromosome 121aa 20 min[#]
19q13.3
hCG Chromosome 145aa 24h
19q13.3

14. Regulation of Circulating Levels of FSH &
LH
Pituitary
Gonad
Hormones
Carbohydrates
Residue
Subunit α > β
Inhibin
Activin
Follistatin
Autocrine/
Paracrine
Mechanism
Sialic Acid
hCG > FSH > LH
slower clearance

15. OVARY
Adult OvaryAdult Ovary
Length: 2-5cm
Width: 1.5-3cm
Thickness: 0.5-1.5cm
Weight: 5-10g
Length: 2-5cm
Width: 1.5-3cm
Thickness: 0.5-1.5cm
Weight: 5-10g
Cortex: germinal epithelium, follicle
Medulla: tissue, contractile cells,
interstitial cells
Hilum : blood vessel, lymp, erves
Cortex: germinal epithelium, follicle
Medulla: tissue, contractile cells,
interstitial cells
Hilum : blood vessel, lymp, erves

16. Ovaries
Functions
Production
of oocytes
Production
of steroid
and
Peptide
Hormones
Embryolo
gy of
Ovary
Endoder
m of yolk
sac
Coelemic
Epithelial
cells
Mesench
ymal
Cells
Primordia
l Germs
Cells
Granulos
a Cells
Ovarian
Stroma

17. Primordial
Cells
Oogonia
Primary
Ooocyte
Primordial
Follicle
Atretic
3rd week of gestation: Yolk Sac
6th week of gestation: Migration into the
gonadal ridge -> generate the primary
sex cords .
Mitosis at
Gonad
12th week of
gestation
Meiosis
Surrounded by
single layer of
flattened granulosa
cells

18. The number of oocytes in the ovary before and
after birth and through Menopause.

19. Meiotic Division during Oocyte
Maturation

20. Ovarian Follicular Development

21. Functional anatomy and developmental
changes in the adult ovary during a ovarian cycle.

22. Steroidogenesis Across the Life Span
Childhood
• 8 weeks' gestation: Ovary →estrogen
• 2nd trimester: Gonadotropin ↑
• The fetal hypothalamic-pituitary axis continues to mature
-> sensitive to estrogen and progesterone -> fetal
gonadotropins fall to low levels prior to birth.
• Newborn: ↑ gonadotropins
• Childhood: The hypothalamic-pituitary axis increased
sensitivity to negative feedback →↓FSH LH
• ↑ FSH:LH ratio : premenarchal girl and postmenopausal
woman.

23. Puberty
• LH secretion ↑. Difference Day & Night
• LH > FSH levels: Reproductive Years
• ↑ LH & FSH → ↑estrogen : growth spurt, maturation of
the female internal and external genitalia, and
development of a female habitus
• Activation of the pituitary-adrenal axis → adrenal
androgen production→axillary and pubic hair (adrenache
or pubarche).
Postmenopause
• Few follicles → ↓estrogen & inhibin → ↑LH and FSH →
androstenedione → estrone but inadequate to protect
against bone loss.

24. Variations in luteinizing hormone (LH) and follicle-stimulating
hormone (FSH) during different life stages in the female.

25. E & P Receptor
Estrogen
Progesteron
+ ligand

26. FOLLICULAR PHASE
• 10–14 day
• A series of sequential actions
of hormones and
autocrine/paracrine peptides
on the follicle
• Follicle destined to ovulate
goes through a period of initial
growth from a primordial
follicle through the stages of
the preantral, antral, and
preovulatory follicle.

27. Primordial Follicle
Primordial follicle in the cortical stroma. A layer of flattened follicular
epithelial cells surrounds the oocyte with its large nucleus and prominent
nucleolus. The ooplasm is not stained

28. • The granulosa cells become cuboidal and
increase in number to form a pseudostratified
layer.
• The decline in luteal phase estrogen,
progesterone, and inhibin-A production by the
now-fading corpus luteum from the previous
cycle
• The increase in FSH that stimulates this follicular
growth.
• Hormone-mediated effects can be transmitted
throughout the follicle.
• Oocyte begins secretion of an acellular coat
known as the zona pellucida.

29. PreAntral Follicle
• The stroma differentiates into the theca
interna, which is adjacent to the basal
lamina, and the theca externa, which
abuts the surrounding stroma
• Oocyte enlarges and is surrounded by a
membrane, the zona pellucida
• Granulosa cells -> estrogens> androgens
or progestins

30. Ovary—Secondary Follicle or Preantral Follicle
1 Follicular epithelium
2 Zona pellucida
3 Basal membrane
4 Theca folliculi

31. Ovary—Secondary Follicle or Preantral Follicle
1 Beginnings of a follicular antrum
2 Theca folliculi interna
3 Theca folliculi externa
4 Cortical stroma
5 Primordial follicle

32. • Specific receptors for FSH are not detected on
granulosa cells until the preantral stage, needed
for androgen aromatase
• The administration of FSH will raise and lower
the concentration of its own receptor on
granulosa cells (up- and down-regulation)

33. Two-Cell Theory of Ovarian Steroidogenesis

34. Antral Follicle ( Tertiary Follicle)
• Follicular fluid begins to collect between
the granulosa cells→ antrum.
• Rapid increase in follicular size
• The granulosa cells surrounding the
oocyte are now designated the cumulus
oophorus

35. • 1 Antrum folliculi
• 2 Cumulus oophorus with oocyte
• 3 Theca folliculi

36. LH Pulse Frequency:
• Early follicular phase —90 minutes.
• Late follicular phase —60–70 minutes.
• Early luteal phase —100 minutes.
• Late luteal phase —200 minutes.
LH Pulse Amplitude:
• Early follicular phase —6.5 IU/L.
• Midfollicular phase —5.0 IU/L.
• Late follicular phase —7.2 IU/L.
• Early luteal phase —15.0 IU/L.
• Midluteal phase —12.2 IU/L.
• Late luteal phase —8.0 IU/L.

37. Gonad Peptide Hormone
• Inhibin: Inhibitor of
FSH secretion.
• Activin: Stimulates
FSH release
• Follistatin : binding
activin: Suppresses
FSH activity

38. INHIBIN
2 Forms of Inhibin:
• Inhibin A: Alpha-BetaA ( Corpus Luteum-Luteal Phase)
• Inhibin B: Alpha-BetaB ( Granulosa Cells-Follicular
Phase )
 Inhibin: block the synthesis and secretion of FSH, reduce
the number of GnRH receptors present, promotes
intracellular degradation of gonadotropins.
 FSH - Inhibin — a reciprocal relationship
 Inhibin B: rises slowly but steadily, in a pulsatile fashion
(60–70 min periodicity) reaching peak levels in the early
and midfollicular phases, a nadir in the midluteal phase.
 Inhibin A: suppression of FSH to nadir levels during the
luteal phase

39. ACTIVIN
• Activin :
• Prior to ovulation: supress Progesteron
production
• Stimulate FSH release and GnRH receptor
number.
• Circulating levels of activin increase in the late
luteal phase to peak at menses
3 Forms of Activin:
• Activin A: BetaA-BetaA
• Activin AB: BetaA-BetaB
• Activin B: BetaB-BetaB

40. Follistatin
• Follistatin playing a
role by inhibiting
activin and enhancing
inhibin activity.

41. Selection Of Dominant Follicle
• The successful conversion to an estrogen
dominant follicle marks the “selection” of a
follicle destined to ovulate -> One Single Follicle
Succeed ->
Dominant Follicle -> Estrogen
• estrogen - FSH interaction (+ for maturing
follicle)
• estrogen - pitutary interaction (- feedback)
-> FSH ↓
Other cells entered Apoptosis -> TNF -> inhibit
FSH stimulation , estradiol secretion

42. PreOvulatory / Graafian Follicle
• Fluid-filled antrum that is composed of plasma
with granulosa-cell secretion
• The oocyte remains connected to the follicle by
cumulus oophorus
• Estrogens - LH (+ feedback) -> Luteinization of
the granulosa cells -> Progesterone &
Prostaglandin -> Initiation of ovulation
• Plasminogen -> Proteolytic enzymes, plasmin

43. • Ovulation will occur in the single mature,
Graafian follicle 10 to 12 hours after the
LH peak or 34 to 36 hours after the initial
rise in midcycle LH.
• Inhibin, Activin and follistatin, insulinlike
growth factor (ILGF)-1, epidermal growth
factor (EGF)/transforming growth factor
(TGF)-α, TGF-β1, β-fibroblast growth
factor (FGF), interleukin-1, tissue necrosis
factor-α, OMI, and renin–angiotensin

44. Ovary—Graafian Follicle
Human follicles reach a
diameter of 20–25mm
1 Antrum folliculi
2 Cumulus oophorus
3 Granulosa epithelial cells
4 Theca folliculi
5 Radial corona cells

45. OVULATION
• Oocyte-cumulus is released from
the follicle
• Toward the end of the follicular
phase, estradiol levels increase
dramatically
• Estradiol - Pituitary (+ Feedback)
• Estradiol concentrations of 200
pg/mL for 50 hours →initiate a
gonadotropin surge
• The mean duration of the LH
surge is 48 hours
• Ovulation occurrs approximately
36 to 40 hours after the onset of
the LH surge

46. • Gn surge -> Plasminogen activity ↑
• Plasmin and collagenase-> follicular
wall thinning
• Prostaglandin-> Ovary muscle
contraction
• Extrusion of the oocyte only lasts a
few minutes

47. LUTEAL PHASE
• The remaining -> corpus
luteum
• granulosa / theca cells
proliferate +
hypertrophy ->
granulosa-lutein cells /
smaller theca-lutein cells
• Basement membrane
degenerates +
vascularize -> Capillary
invasion
• Progesterone Dominant
-> 40 mg of progesterone
per day
• Inhibin A -> low FSH level

48. Corpus Luteum
1 Granulosa
lutein cells
2 Theca lutein
cells
3 Connective
tissue of the
theca folliculi

49. LUTEOLYSIS
• Luteal regression
• Blood supply diminishes
• E & P secretion drop
• Luteal cells apoptosis -> fibrotic -> corpus
albicans

50. The Luteal-Follicular Transition
• Estradiol, progesterone, inhibin -> nadir
• E & P decrease -> increasing GnRH
pusatile
• Inhibin A decrease + increasing GnRH
pulsatile -> FSH > LH

51. UTERUS
• Decidua functionalis
-intermediate zone (stratum spongiosum)
-superficial compact zone (stratum compactum).
• Decidua basalis is the deepest region of the endometrium

52. Proliferative Phase
• Early proliferative phase, the endometrium is
relatively thin (1–2 mm).
• Initially straight, narrow, and short endometrial
glands → longer structures.
• These proliferating glands have multiple mitotic
cells
• Low columnar pattern → pseudostratified pattern
before ovulation.

53. Proliferative Phase
• Proliferative
phase: straight
to slightly
coiled, tubular
glands are lined
by
pseudostratified
columnar
epithelium with
scattered
mitoses.

54. Secretory Phase
Early secretory phase:
• 48-72 hours after
ovulation:
Progesteron↑
• coiled glands lined by
simple columnar
epithelium
• glycogen containing
vacuoles
• Apocrine secretion
• Stroma edema

55. • Late secretory
phase:
• serrated, dilated
glands with
intraluminal
secretion are lined
by short columnar
cells.
• 2 days before
menses: PMN
infilitration→endome
trial stroma collapse

56. • Decidua functionalis
breakdown→menses
• Sex steroids withdrawal:
spiral artery vascular
spasm →endometrial
ischemia.
• Lysosomes breakdown
→proteolytic enzymes
→promote local tissue
destruction.
• Prostaglandin F2α →
potent vasoconstrictor→
arteriolar vasospasm and
endometrial ischemia.
PGF2α also produces
myometrial contractions
Menstrual Phase

57. Effects of Ovarian Steroids on Endometrium
Striking thickening of
endometrial tissue. Stroma
& epithelial proliferate
rapidly.
inhibit or reverse proliferative
action of estrogen.
Differentiation of epthelial &
stroma.