physiology of menstruation
DESCRIPTION
Physiology Of Menstruation By: Nur Afiqah Binti Jasmi (11-2013-031) & Luqman Hakim Bin Mohd Jais (11-2013-170) Dokter Pembimbing: Dr. Harianto Wijaya Sp.OGTRANSCRIPT
![Page 1: Physiology of Menstruation](https://reader033.vdocument.in/reader033/viewer/2022061415/554b322ab4c905d3088b50ce/html5/thumbnails/1.jpg)
Physiology Of Physiology Of MenstruationMenstruation
Disusun Oleh:Nur Afiqah Binti Jasmi 11-2013-031
Luqman Hakim Bin Mohd Jais 11-2013-170Dokter Pembimbing:
dr Harianto Wijaya Sp.OG
Kepaniteraan Klinik Ilmu Obstetri & Ginekologi RSUD TarakanFakultas Kedokteran Ukrida
![Page 2: Physiology of Menstruation](https://reader033.vdocument.in/reader033/viewer/2022061415/554b322ab4c905d3088b50ce/html5/thumbnails/2.jpg)
MENSTRUAL CYCLE
• Menstrual Cycle: 28 ± 7 days . Varied
• Menstrual flow:4 ± 2 days
• Hypothalamus-Pituitary-Ovary Axis
• Hormone Communication
![Page 3: Physiology of Menstruation](https://reader033.vdocument.in/reader033/viewer/2022061415/554b322ab4c905d3088b50ce/html5/thumbnails/3.jpg)
![Page 4: Physiology of Menstruation](https://reader033.vdocument.in/reader033/viewer/2022061415/554b322ab4c905d3088b50ce/html5/thumbnails/4.jpg)
HYPOTHALAMUS
Hypothalamus ----------------------------------------------> Circulating Hormones
Hypothalamus ------------------------------> Pituitary
Hypothalamus ------>Hypothalamus
Long Feedback Loop
Short Feedback Loop
Ultrashort Feedback Loop
![Page 5: Physiology of Menstruation](https://reader033.vdocument.in/reader033/viewer/2022061415/554b322ab4c905d3088b50ce/html5/thumbnails/5.jpg)
REPRODUCTIVE FUNCTIONS OF THE HYPOTHALAMUSGonadotropin-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
![Page 6: Physiology of Menstruation](https://reader033.vdocument.in/reader033/viewer/2022061415/554b322ab4c905d3088b50ce/html5/thumbnails/6.jpg)
Neuronal Body Neuronal Body
Pre-pro-GnRHPre-pro-GnRH
GnRH decapeptideGAP
GnRH decapeptideGAP
Portal VesselPortal Vessel
ProteolyticProteolytic
Nerve terminalNerve terminal
GnRH geneGnRH gene
![Page 7: Physiology of Menstruation](https://reader033.vdocument.in/reader033/viewer/2022061415/554b322ab4c905d3088b50ce/html5/thumbnails/7.jpg)
GnRH Pulsatile Secretion
Continuous Exposure
Downregulation
GnRH receptor decrease
Intermittent Exposure
UpregulationAutoprime
GnRH receptor increase
![Page 8: Physiology of Menstruation](https://reader033.vdocument.in/reader033/viewer/2022061415/554b322ab4c905d3088b50ce/html5/thumbnails/8.jpg)
![Page 9: Physiology of Menstruation](https://reader033.vdocument.in/reader033/viewer/2022061415/554b322ab4c905d3088b50ce/html5/thumbnails/9.jpg)
Follicular Phase Luteal PhaseMid Follicular
![Page 10: Physiology of Menstruation](https://reader033.vdocument.in/reader033/viewer/2022061415/554b322ab4c905d3088b50ce/html5/thumbnails/10.jpg)
Endogenous Opioids and Effects on GnRH
Opioid Endorphin ↑ Inhibit GnRH releases
Ovarian Sex Streoids
EndorphinPeak: Luteal PhaseNadir: Menses
![Page 11: Physiology of Menstruation](https://reader033.vdocument.in/reader033/viewer/2022061415/554b322ab4c905d3088b50ce/html5/thumbnails/11.jpg)
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.
![Page 12: Physiology of Menstruation](https://reader033.vdocument.in/reader033/viewer/2022061415/554b322ab4c905d3088b50ce/html5/thumbnails/12.jpg)
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
![Page 13: Physiology of Menstruation](https://reader033.vdocument.in/reader033/viewer/2022061415/554b322ab4c905d3088b50ce/html5/thumbnails/13.jpg)
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
![Page 14: Physiology of Menstruation](https://reader033.vdocument.in/reader033/viewer/2022061415/554b322ab4c905d3088b50ce/html5/thumbnails/14.jpg)
Regulation of Circulating Levels of FSH & LH
Pituitary
Gonad Hormones
CarbohydratesResidue
Subunit α > β
InhibinActivinFollistatin
Autocrine/ParacrineMechanism
Sialic AcidhCG > FSH > LHslower clearance
![Page 15: Physiology of Menstruation](https://reader033.vdocument.in/reader033/viewer/2022061415/554b322ab4c905d3088b50ce/html5/thumbnails/15.jpg)
OVARY
Adult OvaryAdult Ovary
Length: 2-5cmWidth: 1.5-3cm
Thickness: 0.5-1.5cmWeight: 5-10g
Length: 2-5cmWidth: 1.5-3cm
Thickness: 0.5-1.5cmWeight: 5-10g
Cortex: germinal epithelium, follicleMedulla: tissue, contractile cells,
interstitial cellsHilum : blood vessel, lymp, erves
Cortex: germinal epithelium, follicleMedulla: tissue, contractile cells,
interstitial cellsHilum : blood vessel, lymp, erves
![Page 16: Physiology of Menstruation](https://reader033.vdocument.in/reader033/viewer/2022061415/554b322ab4c905d3088b50ce/html5/thumbnails/16.jpg)
Ovaries Functions
Production of oocytes
Production of steroid
and Peptide
Hormones
Embryology of
Ovary
Endoderm of yolk
sac
Coelemic Epithelial
cells
Mesenchymal Cells
Primordial Germs
Cells
Granulosa Cells
Ovarian Stroma
![Page 17: Physiology of Menstruation](https://reader033.vdocument.in/reader033/viewer/2022061415/554b322ab4c905d3088b50ce/html5/thumbnails/17.jpg)
Primordial Cells
Oogonia
Primary Ooocyte
Primordial Follicle
Atretic
3rd week of gestation: Yolk Sac6th 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
![Page 18: Physiology of Menstruation](https://reader033.vdocument.in/reader033/viewer/2022061415/554b322ab4c905d3088b50ce/html5/thumbnails/18.jpg)
The number of oocytes in the ovary before and after birth and through Menopause.
![Page 19: Physiology of Menstruation](https://reader033.vdocument.in/reader033/viewer/2022061415/554b322ab4c905d3088b50ce/html5/thumbnails/19.jpg)
Meiotic Division during Oocyte Maturation
![Page 20: Physiology of Menstruation](https://reader033.vdocument.in/reader033/viewer/2022061415/554b322ab4c905d3088b50ce/html5/thumbnails/20.jpg)
Ovarian Follicular Development
![Page 21: Physiology of Menstruation](https://reader033.vdocument.in/reader033/viewer/2022061415/554b322ab4c905d3088b50ce/html5/thumbnails/21.jpg)
Functional anatomy and developmental changes in the adult ovary during a ovarian cycle.
![Page 22: Physiology of Menstruation](https://reader033.vdocument.in/reader033/viewer/2022061415/554b322ab4c905d3088b50ce/html5/thumbnails/22.jpg)
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.
![Page 23: Physiology of Menstruation](https://reader033.vdocument.in/reader033/viewer/2022061415/554b322ab4c905d3088b50ce/html5/thumbnails/23.jpg)
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.
![Page 24: Physiology of Menstruation](https://reader033.vdocument.in/reader033/viewer/2022061415/554b322ab4c905d3088b50ce/html5/thumbnails/24.jpg)
Variations in luteinizing hormone (LH) and follicle-stimulating hormone (FSH) during different life stages in the female.
![Page 25: Physiology of Menstruation](https://reader033.vdocument.in/reader033/viewer/2022061415/554b322ab4c905d3088b50ce/html5/thumbnails/25.jpg)
E & P Receptor
Estrogen
Progesteron
+ ligand
![Page 26: Physiology of Menstruation](https://reader033.vdocument.in/reader033/viewer/2022061415/554b322ab4c905d3088b50ce/html5/thumbnails/26.jpg)
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.
![Page 27: Physiology of Menstruation](https://reader033.vdocument.in/reader033/viewer/2022061415/554b322ab4c905d3088b50ce/html5/thumbnails/27.jpg)
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
![Page 28: Physiology of Menstruation](https://reader033.vdocument.in/reader033/viewer/2022061415/554b322ab4c905d3088b50ce/html5/thumbnails/28.jpg)
• 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.
![Page 29: Physiology of Menstruation](https://reader033.vdocument.in/reader033/viewer/2022061415/554b322ab4c905d3088b50ce/html5/thumbnails/29.jpg)
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
![Page 30: Physiology of Menstruation](https://reader033.vdocument.in/reader033/viewer/2022061415/554b322ab4c905d3088b50ce/html5/thumbnails/30.jpg)
Ovary—Secondary Follicle or Preantral Follicle
1 Follicular epithelium2 Zona pellucida3 Basal membrane4 Theca folliculi
![Page 31: Physiology of Menstruation](https://reader033.vdocument.in/reader033/viewer/2022061415/554b322ab4c905d3088b50ce/html5/thumbnails/31.jpg)
Ovary—Secondary Follicle or Preantral Follicle
1 Beginnings of a follicular antrum2 Theca folliculi interna3 Theca folliculi externa4 Cortical stroma5 Primordial follicle
![Page 32: Physiology of Menstruation](https://reader033.vdocument.in/reader033/viewer/2022061415/554b322ab4c905d3088b50ce/html5/thumbnails/32.jpg)
• 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)
![Page 33: Physiology of Menstruation](https://reader033.vdocument.in/reader033/viewer/2022061415/554b322ab4c905d3088b50ce/html5/thumbnails/33.jpg)
Two-Cell Theory of Ovarian Steroidogenesis
![Page 34: Physiology of Menstruation](https://reader033.vdocument.in/reader033/viewer/2022061415/554b322ab4c905d3088b50ce/html5/thumbnails/34.jpg)
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
![Page 35: Physiology of Menstruation](https://reader033.vdocument.in/reader033/viewer/2022061415/554b322ab4c905d3088b50ce/html5/thumbnails/35.jpg)
• 1 Antrum folliculi • 2 Cumulus oophorus with oocyte• 3 Theca folliculi
![Page 36: Physiology of Menstruation](https://reader033.vdocument.in/reader033/viewer/2022061415/554b322ab4c905d3088b50ce/html5/thumbnails/36.jpg)
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.
![Page 37: Physiology of Menstruation](https://reader033.vdocument.in/reader033/viewer/2022061415/554b322ab4c905d3088b50ce/html5/thumbnails/37.jpg)
Gonad Peptide Hormone
• Inhibin: Inhibitor of FSH secretion.
• Activin: Stimulates FSH release
• Follistatin : binding activin: Suppresses FSH activity
![Page 38: Physiology of Menstruation](https://reader033.vdocument.in/reader033/viewer/2022061415/554b322ab4c905d3088b50ce/html5/thumbnails/38.jpg)
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
![Page 39: Physiology of Menstruation](https://reader033.vdocument.in/reader033/viewer/2022061415/554b322ab4c905d3088b50ce/html5/thumbnails/39.jpg)
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
![Page 40: Physiology of Menstruation](https://reader033.vdocument.in/reader033/viewer/2022061415/554b322ab4c905d3088b50ce/html5/thumbnails/40.jpg)
Follistatin
• Follistatin playing a role by inhibiting activin and enhancing inhibin activity.
![Page 41: Physiology of Menstruation](https://reader033.vdocument.in/reader033/viewer/2022061415/554b322ab4c905d3088b50ce/html5/thumbnails/41.jpg)
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
![Page 42: Physiology of Menstruation](https://reader033.vdocument.in/reader033/viewer/2022061415/554b322ab4c905d3088b50ce/html5/thumbnails/42.jpg)
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
![Page 43: Physiology of Menstruation](https://reader033.vdocument.in/reader033/viewer/2022061415/554b322ab4c905d3088b50ce/html5/thumbnails/43.jpg)
• 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
![Page 44: Physiology of Menstruation](https://reader033.vdocument.in/reader033/viewer/2022061415/554b322ab4c905d3088b50ce/html5/thumbnails/44.jpg)
Ovary—Graafian FollicleHuman follicles reach a
diameter of 20–25mm
1 Antrum folliculi 2 Cumulus oophorus 3 Granulosa epithelial cells4 Theca folliculi5 Radial corona cells
![Page 45: Physiology of Menstruation](https://reader033.vdocument.in/reader033/viewer/2022061415/554b322ab4c905d3088b50ce/html5/thumbnails/45.jpg)
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
![Page 46: Physiology of Menstruation](https://reader033.vdocument.in/reader033/viewer/2022061415/554b322ab4c905d3088b50ce/html5/thumbnails/46.jpg)
• Gn surge -> Plasminogen activity ↑• Plasmin and collagenase-> follicular
wall thinning• Prostaglandin-> Ovary muscle
contraction• Extrusion of the oocyte only lasts a
few minutes
![Page 47: Physiology of Menstruation](https://reader033.vdocument.in/reader033/viewer/2022061415/554b322ab4c905d3088b50ce/html5/thumbnails/47.jpg)
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
![Page 48: Physiology of Menstruation](https://reader033.vdocument.in/reader033/viewer/2022061415/554b322ab4c905d3088b50ce/html5/thumbnails/48.jpg)
Corpus Luteum
1 Granulosa lutein cells 2 Theca lutein cells3 Connective tissue of the theca folliculi
![Page 49: Physiology of Menstruation](https://reader033.vdocument.in/reader033/viewer/2022061415/554b322ab4c905d3088b50ce/html5/thumbnails/49.jpg)
LUTEOLYSIS
• Luteal regression
• Blood supply diminishes
• E & P secretion drop
• Luteal cells apoptosis -> fibrotic -> corpus albicans
![Page 50: Physiology of Menstruation](https://reader033.vdocument.in/reader033/viewer/2022061415/554b322ab4c905d3088b50ce/html5/thumbnails/50.jpg)
The Luteal-Follicular Transition
• Estradiol, progesterone, inhibin -> nadir• E & P decrease -> increasing GnRH
pusatile • Inhibin A decrease + increasing GnRH
pulsatile -> FSH > LH
![Page 51: Physiology of Menstruation](https://reader033.vdocument.in/reader033/viewer/2022061415/554b322ab4c905d3088b50ce/html5/thumbnails/51.jpg)
UTERUS
• Decidua functionalis
-intermediate zone (stratum spongiosum)
-superficial compact zone (stratum compactum). • Decidua basalis is the deepest region of the endometrium
![Page 52: Physiology of Menstruation](https://reader033.vdocument.in/reader033/viewer/2022061415/554b322ab4c905d3088b50ce/html5/thumbnails/52.jpg)
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.
![Page 53: Physiology of Menstruation](https://reader033.vdocument.in/reader033/viewer/2022061415/554b322ab4c905d3088b50ce/html5/thumbnails/53.jpg)
Proliferative Phase
• Proliferative phase: straight to slightly coiled, tubular glands are lined by pseudostratified columnar epithelium with scattered mitoses.
![Page 54: Physiology of Menstruation](https://reader033.vdocument.in/reader033/viewer/2022061415/554b322ab4c905d3088b50ce/html5/thumbnails/54.jpg)
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
![Page 55: Physiology of Menstruation](https://reader033.vdocument.in/reader033/viewer/2022061415/554b322ab4c905d3088b50ce/html5/thumbnails/55.jpg)
• Late secretory phase:
• serrated, dilated glands with intraluminal secretion are lined by short columnar cells.
• 2 days before menses: PMN infilitration→endometrial stroma collapse
![Page 56: Physiology of Menstruation](https://reader033.vdocument.in/reader033/viewer/2022061415/554b322ab4c905d3088b50ce/html5/thumbnails/56.jpg)
• 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
![Page 57: Physiology of Menstruation](https://reader033.vdocument.in/reader033/viewer/2022061415/554b322ab4c905d3088b50ce/html5/thumbnails/57.jpg)
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.
![Page 58: Physiology of Menstruation](https://reader033.vdocument.in/reader033/viewer/2022061415/554b322ab4c905d3088b50ce/html5/thumbnails/58.jpg)