Flashcards in Menstruation, menopause Deck (25)
Produced from cholesterol by granulosa cells of ovaries (due to FSH) Oestradiol (E2) is most potent, but oestriol is in pregnancy and oestrone is produced in post menopausal women
P4. Produced by corpus luteum (then placenta if pregnant). Gives negative feedback to hypothalamus (GnRH) and ant. pit (LH/FSH)
Stimulates granulose differentiation/oestrogen production. Stimulated by GnRH
Stimulated by GnRH. Stimulates Thexa cells to secrete androgens, and granulosa cells can convert angrodens to oestrogen. After ovulation, LH stimulates follicle maturation into corpus luteum (secretes oestrogen and progesterone)
Two menstrual phases
Phase 1 is proliferation (under oestrogen control) around 14 days. Secretory phase is progesterone controlled - allows glands and spiral arteries to change morphology and undergo decidualisation. Glycogen droplets embed for pregnancy.
perimetrium, then myometrium, then stratum basalis and then stratum functionalis. Functional is sloughed off (Prostaglandin mediated),and basal allows regeneration.
FSH rises at beginning of cycle (due to feedback from low oestrogen and prog.). As FSG rises, more follicles secrete oestrogen, once threshold exceeded then LH surge, triggering ovulation and corpus luteum development. Empty follicle release prog. If no fert. then corpus luteum dies.
Act on FSH to stop follicle recruitment. B peaks in follicular phase, A peaks in luteal phase.
To summarise, at the start of the menstrual cycle (during bleeding), E2 and P2 are low which allows GnRH induced FSH secretion from anterior pituitary (days 1-7). During days 8-14, FSH is developing a follicle (dominant follicle) which also secretes E2. Once a treshold has been passed in terms of FSH, an LH surge is triggered which triggers ovulation (24-36 hours afterwards). During days 14-28, LH causes the empty follicle to become a corpus luteum which then secretes progesterone and E2, and progesterone then prepares the endometrium for implantation (morphological changes in the glands, decidualisation, glycogen deposits).
If no fertilisation the corpus luteum degenerates and P4 drops. Prostaglandins cause vasoconstriction and ischaemia which leads to menses.
Progesterone and cAMP process. Cells become secretory and glycogen/lipid rich. Cells also secrete prolactin. Uterine NK promote immunotolerance. Decidualisation impaired in miscarriage and endometriosis.
Oestrogen prevents follicular development and leutinisation. Progestion makes c. mucus hostile to sperm. General ADEs: wt gain, libido loss, chloasma (hyperpigmentation), breast tenderness.
CV ADEs: HT, DVT, MI, stroke.
GI ADEs: N&V, LFT abnormalities, gallstones, hepatic tumours
Nervous ADEs: headache, migraine, depression
Maligancy: Increased breast cancer risk, reduced ovarian/endometrial cancer.
Gynae: amenorrhoea, spotting, cervical erosion
Endocrine: mild glucose intolerance, worsens lipid profile
Hazard in smokers, obese women and women with increased CV factors
Progesterone only, less effective but used in breastfeeding women, smokers, CV risk
High dose progesterone to thicken cervical mucus
HPO dysfunction causes
Disordered GnRH release due to stress, strenuous exercise, excessive weight gain, anorexia, jet lag. Endocrine (prollactinaemia, hyper/hypothyroid/Cushing's
Possible causes are retrograde menstruation, inflammation/cytokines, angiogenesis disorders. COCP, GnRH and surgery can help improve symptoms.
Can be treated with levonorgestrel IU (LNG-IUS or Mirena Coil) - effective contraceptive, improves dysmenorrhoea, few side effects.
Can also use tranexamic acid (antifibrinolytic agent), mefenamic acid (NSAID), COCP (but caution on ADEs and risk factors), oral progesterone taken on days 6-26 (but no contraceptive).
Ulipristal acetate (progesterone antagonist) be used for large fibroids, but can cause liver injury
GnRH agonists can cause amenorrhoea, but can only be used for short periods (otherwise causes osteoporosis through lack of oestrogen).
Surgical options: endometrial ablation, hysterectomy
Medulla (blood vessels), cortex (follicles), germinal epithelium
Primordial germ cells at yolk sac, migrate to genital ridge at 6 weeks), then prolferate and differentiate into oogonia (7 million), arresting at prophase 1. Depleted till birth, depletion slows till puberty, slows further till approaching menopause.
Every day, cohort grows and every 3-4 months a primary follicle is selected. By 70 days, antral follicles (2-5mm) forms - can respond to FSH and be rescued. Follicles secrete oestrogen and inhibin (reduce FSH), and once FSH drops, follicles <8mm die off, so only 8-10mm dominant follicles survive. Matures into graafian (20mm). Dominant secretes oestrogen, becomes positive feedback loop for FSH and LH. FSH window allows one oocyte per cycle, but window windened during IVF.
WHO 1 anovulation
WHO1 is "upstairs failure" - > hypogonadotrophic hypogonadism (hypothalamus/pit non functioning). Low FSH, Low E2. Hypothalamic failure can be nutritional/psychologcal, but can be organic in Kallman's syndrome. Pituitary failure can be congenital, Sheehan disease, radiotherapy, trauma, neoplasia
WHO 2 anovulation
"downstairs failure" - Menopause of ovary stops Normogonadotrophic normogonadism. Oligo/amenorrhoea. Causes include PCOS, HPO dysfunction or extra HPO dysfunction (includes obsesity (hormone imbalance), hyperprolactinaemia, hypothyroidism, adrenal disease)
WHO group 3
Ovary not working (so no oestrogen). Hypergonadotrophic hypogonadism. High FSH, low E2.
Can be turners, autoimmune mediated, ovarial pathology (viral infection, endometriosis), iatrigenic, idiopathic. Idiopathic is most common
Ovulation can be detected by:
Mid cycle pain/bleeding, LH surge, day 21 progesterone peak, U/S follicle tracking or endometrial biopsy for post ovulatory change.
Associated with high androgen levels (possibly through LH mediation) and also associated with insulin resistance.
Could be ovarian dysfunction - > excess androgen - > LH-> androgen. Could be pit dysfunction fiving excess LH - > androgen. Could be met. syndrome with hyperinsulinaemia and androgen excess.
PCOS androgen effects
Causes follicular arrest in small antral phase, follicles escape atresia AND selection, so more and more get stuck. Also causes acne, hirsutism, baldness