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
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
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.
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)
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
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
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
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.
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
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.