Gyna : physiology of menstruation

sizes of primordial follicle , preantral follicle preovulatory follicles

50u,200u, 18-24mm

premordial follicle

primary oocytes arrested in prophase 1

surrounded by single layer of pre granulosa cells

describe follicular growth

FSH stimulate increased growth so inc E2 production that stimulates formation of more FSH receptors more follicular growth (vicious cycle)

what is zona pellucida in preantral follicle and its effect

a hyaline membrane is formed around oocyte and limits further inc in size

describe membrane granulose on preantral follicle

pre granulosa cells are cuboidal and proliferate forming layers of granulose cells

what are liquor folluci on preantral follicle

fluid spaces start to appear between the granulose cells (liqour follucli)

what are theca interna cells on premordial follice

surrounding parenchymal cells (theca interna)

describe follicular selection

the high E2 (and inhibin) inhibit FSH so decrease aromatization and increase local androgen so atresia of most follicles

antral (dominant) follicle

is immune aganist atresia as it has large number of FSH receptors

fluid spaces between granulosa cells join together to form large antrum full of estrogen

mid cyclic surge

presistant high E2 >200 for 50hrs stimulate positive feedback

cause LH surge

cause FSH smaller surge (2nd surge)

effect of lh surge

stimulate androgen production theca cells to 1-ensure atresia of non dominant follicles

2-increase libido midcycle

3- ovulation within 36 hours

preovulatory follicle

oocyte resumes the prophase of meiosis 1 so have haploid half number of chromosomes and first polar body

layers of mature graffian follicle

Theca externa

Theca interna

Membrana granulosa

antrum follicle

cumulus oophorus

Corona radiata

Zona pellucida

Perivitelline space

Ovum

Ovulation timing

Occurs \~36 hrs after LH surge

Process of ovulation

Dominant follicle ruptures → oocyte + follicular fluid into peritoneal cavity

Theories of ovulation mechanism

(1) Proteolytic enzymes (collagenase, hyaluronidase) (2) Ovarian smooth muscle contraction (PG-mediated) (3) Pressure effect from antrum folliculi

Why is the mid-cycle LH surge short-lived?

(a) Pituitary LH storage exhaustion (b) Loss of estrogen positive feedback

Corpus luteum formation proliferative stage

granulosa & theca cells multiply

corpus luteum formation Luteinization phase

cholesterol deposition → steroidogenesis of E + P

what happens in corpus luteum Vascularization phase

→ mature CL

Granulosa cells in luteal phase Form

lutein cells

Theca cells in luteal phase Form

paralutein cells

Peak estrogen & progesterone in luteal phase

Around day 21

Fate of CL without pregnancy

CL regression → inc E & P → negative feedback → FSH/LH → new cycle

cl degeneration

degenerates from day 22 → corpus albicans → corpus fibrosum → menstruation

commence of new cycle

dec e and p menses release of negative feed back on lh and fsh so they inc and start of new cycle

Fate of CL with pregnancy

Maintained by hCG → continues E2 + P production until 12 weeks (placenta takes over)

proliferative phase of endometrial cycle coincides with

overian follicular phase due to effect of e2 of GF

Endometrial thickness in proliferative phase from start to end

0.5 mm post-menstruation → 5-8 mm by end of phase

Histology in proliferative phase

-Glandular epithelium growth: low columnar → pseudostratified with mitoses

-stromal growth

Secretory phase changes - early

Subnuclear vacuoles → released into endometrial cavity

Secretory phase changes - mid

Peak secretion(implantation window) (7 days after LH surge), large granulated lymphocytes (NK cells) regulate trophoblastic invasion

Secretory phase changes - late

3 layers visible: basalis, spongiosum (gland bodies), compactum (gland necks); glands & arteries tortuous

Progesterone effect on endometrium

Inhibits E-induced proliferation, limits thickness, induces secretory changes

Mechanism of menstruation

CL regression → ↓P → shrinkage/edema → lysosomal breakdown → PG (F2α) → vasospasm/myometrial contraction → ischemia → necrosis/shedding → bleeding

Composition of menstrual blood

75% arterial, 25% venous; no clots (fibrinolysis); contains endometrial shreds, cervical mucus, leukocytes, vaginal epithelium, bacteria

Cessation of menstruation

Vasoconstriction + hemostatic plug

Regeneration of endometrium

From zona basalis (hormone-insensitive)

Cervical mucus in follicular phase

Copious watery discharge, low viscosity, spinnbarkeit +ve (stretch up to 10 cm), fern test +ve, leukocytes ↓

Cervical mucus in luteal phase

Scanty viscid discharge, thick, spinnbarkeit -ve, fern test -ve, leukocytes ↑

Fern test

Dried cervical mucus under microscope shows arborization pattern (E2 effect)

Spinnbarkeit test

Mucus stretched into thread between slides (E2 effect)

Vaginal smear in follicular phase

Estrogenic smear: mature superficial polygonal acidophilic cells with pyknotic nuclei

mat index in follicular phase

maturation index 0-30-70

vaginal acidity and lymphocytes in follicular phase

more acidity less lymphocytes

Vaginal smear in luteal phase

Progesteronic smear: intermediate navicular basophilic cells;

mat index in luteal phase

maturation index 0-70-30

vaginal acidity and lymphocytes in luteal phase

less acidity more lymphocytes

Cause of vaginal acidity in follicular phase

Glycogen → Doderlein's bacilli → lactic acid

Tubal cycle proliferative phase

more vascularity, muscle hypertrophy, more peristalsis

Tubal cycle secretory phase

more secretion, less motility

Most potent estrogen

Estradiol (E2)

Estrogen sources

Ovary (follicles, CL), placenta, adrenal cortex

adipose tissue conversion

Estrogen metabolism

99% bound (SHBG), metabolized in liver

Estrogen effect on bone

stimulate osteoblasts, growth spurt, epiphyseal closure, anti-osteoporosis

estrogen effect on breast

duct and fat growth

estrogen effect on pitutary gland

-ve feedback on GnRH (except +ve >200 pg/ml for 50 hrs) ↑Prolactin release but blocks actio

estrogen effect on blood vessels and renal system

Vasodilatation

Salt/water retention

estrogen effect on carbohydrates

anti insulin action

estrogen effect of lipids and ISHD

inc HDL dec LDL

protective

estrogen effect on protien

Protein anabolic

estrogen effect on coagulation

↑Coagulation factors ↓fibrinolysis (↑thrombosis risk)

estrogen effect on binding globulins

increase all

Estrogen genital actions

Vaginal, cervical, uterine, tubal proliferation & vascularity

progesterone types

natural micronised and 17 oh progesterone

Progesterone sources

CL, placenta, adrenals

Progesterone action on temp

inc Basal body temp

progesterone effect on breast

alveolar development

progesterone effect on pitutary

-ve feedback blocks ovulation

progesterone effect on smooth muscle

relaxation (GIT, ureter)

progesterone action of resp system

inc resp depth

Progesterone genital actions

Induces secretory changes in endometrium

Effect of estrogen + progesterone on myometrium

Both → hypertrophy

E increases contractility

P relaxes

clinical uses of estrogen

contraception , mestrual irregularities , ERT , infertility , infections

clinical uses of progesterone

contraception , mestrual irregularities , PRT , abortions CLI

actions of unopposed complications

endometriosis, endometrial hyperplasia, endometrial carcinoma.

gonadotrophins molecular

glycoprotiens having similar a and different b

source of gonadotrophins

FSH LH by ant pitutary (basophils)

HCG by trophoblasts

FSH actions in female

Stimulates follicular development, granulosa cell steroidogenesis, induces granulosa FSH & LH receptors

FSH actions in male

Stimulates spermatogenesis (via Sertoli cells)

LH actions in female

Theca cell steroidogenesis, LH surge → ovulation, luteinization of granulosa → CL maintenance

LH actions in male

Stimulates Leydig cells → testosterone production

hCG actions in female

Maintains CL until 12 weeks, stimulates steroidogenesis

hCG actions in male fetus

Stimulates fetal testicular descent

Clinical uses of FSH/LH

Hypothalamic-pituitary failure, clomiphene-resistant anovulation, unexplained infertility, controlled ovarian hyperstimulation in ART, male infertility

Clinical uses of hCG

Trigger ovulation (5,000-10,000 IU IM mimics LH surge), luteal phase support (CL insufficiency, threatened abortion)

pitutary anatomy

lies in sella turcica, covered by diaphragma sella, connected via stalk.

that is released from ant pituraty

GH, prolactin, FSH, LH, TSH, ACTH.

what is released in post pituraty

oxytocin, ADH (formed in hypothalamus).

pitutary lies behind ..... and on each side there is ......

optic chiasm

cavernous sinus

GnRH characteristics

Decapeptide, pulsatile every 60-90 min

neurotansmitters control on GnRH

inc by noradrenaline dec by dopamine, serotonin, β-endorphins, melatonin

GnRH feedback loops

Long loop (ovarian steroids), short loop (Gn), ultrashort loop (GnRH inhibits itself)

GnRH therapeutic uses in pulsatile manner

Pulsatile: ovulation induction

GnRH therapeutic uses in continious manner

Continuous: receptor downregulation → ↓FSH/LH → ↓E; Clinical: ART, contraception, precocious puberty, hirsutism, E-dependent tumors (fibroids, endometrial hyperplasia/cancer, AUB-O)

Normal hormone levels of estrogen and progesterone

30-75 pg/ml

>10 ng/ml

normal hormonal levels of testosterone in female

0.2-0.8 ng/ml

normal hormonal levels of FSH and LH

5-30 mIU/ml , 5-20 mIU/ml

normal prolactin levels

2-20 ng/ml