2. Female Hormonal Cycle MENSTRUAL CYCLE Female Hormonal Cycle MENSTRUAL CYCLE by : S. Rouholamin MD

3. Reproductive hormones: GnRH GnRH: decapeptide, by neurons in arcuate nucleus of hypothalamus GnRH: decapeptide, by neurons in arcuate nucleus of hypothalamus Regulate secretion of two hormones: FSH and LH Regulate secretion of two hormones: FSH and LH Pulsatile secretion Pulsatile secretion Extremely short half-life: only 2-4 min Extremely short half-life: only 2-4 min

4. Gonodotropins LH &FSH: by ant pituitary gonadotroph cells LH &FSH: by ant pituitary gonadotroph cells Ovarian follicular stimulation Ovarian follicular stimulation Glycoproteins, alpha &beta subunit Glycoproteins, alpha &beta subunit

5. Prolactin Poly peptide, by ant pituitary lactotroph Poly peptide, by ant pituitary lactotroph Primary trophic factor responsible for the synthesis of milk by breast Primary trophic factor responsible for the synthesis of milk by breast PRL secretion is under tonic inhibitory control by hypothalamic secretion of dopamine PRL secretion is under tonic inhibitory control by hypothalamic secretion of dopamine PRL stimulation: breast manipulation, drugs, stress, exercise, certain foods PRL stimulation: breast manipulation, drugs, stress, exercise, certain foods

6. TSH By ant pituitary thyrotrophs in response to TRH By ant pituitary thyrotrophs in response to TRH TRH:by arcuate nucleus,portal circulation, pituitary TRH:by arcuate nucleus,portal circulation, pituitary TRH: TSH & PRL release TRH: TSH & PRL release Hypo- and hyperthyroidism: ovulatory dysfunction Hypo- and hyperthyroidism: ovulatory dysfunction

7. Oxytocin 9 aa peptide, by paraventricular nucleus of hypothalamus 9 aa peptide, by paraventricular nucleus of hypothalamus Uterine muscular contraction, breast lactiferous duct myoepithelial contraction Uterine muscular contraction, breast lactiferous duct myoepithelial contraction

8. MENSTRUAL CYCLE Normal cycle length is considered 28 days Normal cycle length is considered 28 days varies from female to female (21-35 days) varies from female to female (21-35 days) Ovarian cycle: 1-follicular,2-luteal Ovarian cycle: 1-follicular,2-luteal Uterine cycle: 1-proliferative,2-secreatory Uterine cycle: 1-proliferative,2-secreatory

9. 1 – Follicular phase Development dominant follicle, mature at midcycle, ovulation Development dominant follicle, mature at midcycle, ovulation Average length:10-14 days Average length:10-14 days Variability in length: variations in total cycle length Variability in length: variations in total cycle length

10. 2-luteal phase Ovulation to menses Ovulation to menses Average length: 14 days Average length: 14 days

11. Normal menstrual cycle 21-35 days 21-35 days 2-6 days of flow 2-6 days of flow Average blood loss:20-60 ml Average blood loss:20-60 ml

13. Hormonal variations 1. At the beginning of cycle: levels of gonadal steroids are low 2. Demise of corpus luteum, FSH levels rise, cohort of growing follicles is recruited, rise in estrogen: stimulus for uterine endometrial proliferation

14. 3. Rising estrogen levels: negative feedback on pituitary FSH secretion; growing follicle produce inhibin-B: suppresses pituitary FSH secretion; growing follicle produce inhibin-B: suppresses pituitary FSH secretion; Rising estrogen levels: LH initially decreases Rising estrogen levels: LH initially decreases but late in follicular phase LH levels increased dramatically but late in follicular phase LH levels increased dramatically Hormonal variations

15. 4. At the end of follicular phase (just before ovulation) FSH-induced LH receptors on granulosa cells; with LH stimulation, modulate secretion of progesterone with LH stimulation, modulate secretion of progesterone Hormonal variations

16. 5. After sufficient degree of estrogenic stimulation; pituitary LH surge triggered, proximate cause of ovulation occurs 24 to 36 hours later Hormonal variations

17. 6. Estrogen level decreases through the early luteal phase from just before ovulation until midluteal phase, rise again as a result of corpus luteum secretion Hormonal variations

18. 7. Progesteron levels rise after ovulation; presumptive sign of ovulation 8. Progesteron;estrogen and inhibin-A : suppress gonadotropin secretion and new follicular growth Hormonal variations

20. Cyclic changes of the Endometrium Decidua functionalis: 2/3 superficial, proliferate and shed each cycle Decidua functionalis: 2/3 superficial, proliferate and shed each cycle Decidua basalis: deepest region, source of endometrial regeneration after each menses Decidua basalis: deepest region, source of endometrial regeneration after each menses

22. 1-Proliferative phase First day of vaginal bleeding :day 1 of the menstrual cycle First day of vaginal bleeding :day 1 of the menstrual cycle Progressive mitotic growth of decidua functionalis, preparation for implantation of embryo Progressive mitotic growth of decidua functionalis, preparation for implantation of embryo Thin endometrium (1-2 mm); straight, narrow, short endometrial glands become longer, tortuous structures Thin endometrium (1-2 mm); straight, narrow, short endometrial glands become longer, tortuous structures

23. 2-Secretory phase 48 to 72 hours following ovulation, progesteron secretion: eosinophilic protein-rich secretory product in glandular lumen 48 to 72 hours following ovulation, progesteron secretion: eosinophilic protein-rich secretory product in glandular lumen Postovulatory day 6-7,maximal secretory activity: optimal for implantation of blastocyst Postovulatory day 6-7,maximal secretory activity: optimal for implantation of blastocyst Stromal edema in late secretory phase Stromal edema in late secretory phase

24. 2 days before menses:dramatic increases in PMN migrate from vascular system 2 days before menses:dramatic increases in PMN migrate from vascular system 2-Secretory phase

25. Menses Absence of implantations, glandular secretion ceases, irregular break-down of decidua fuctionalis Absence of implantations, glandular secretion ceases, irregular break-down of decidua fuctionalis Destruction of corpus luteum and its productions estrogen and progesteron: cause of shedding Destruction of corpus luteum and its productions estrogen and progesteron: cause of shedding Withdrawal of sex steroids: spiral art spasm, endometrial ischemia, lysosoms breakdown, proteolytic enzymes release Withdrawal of sex steroids: spiral art spasm, endometrial ischemia, lysosoms breakdown, proteolytic enzymes release

27. Ovarian follicular development Fetus:6-7 million in 20 wks Fetus:6-7 million in 20 wks At birth:1-2 million At birth:1-2 million At puberty:300,000 At puberty:300,000 Release during ovulation:400-500 Release during ovulation:400-500 At menopause:rare At menopause:rare

29. Oogonia: only one final daughter cell (oocyte), three polar body Oogonia: only one final daughter cell (oocyte), three polar body Oocyte arrested in prophase (diploten) until time of ovulation Oocyte arrested in prophase (diploten) until time of ovulation

30. with LH stimulation, the ovarian theca cells produce androgens that convert by granulosa cells into estrogens under the stimulus of FSH with LH stimulation, the ovarian theca cells produce androgens that convert by granulosa cells into estrogens under the stimulus of FSH Two-cell two-gonadotropin theory