The menstrual cycle involves two main phases - the follicular phase and luteal phase. In the follicular phase, hormones stimulate the growth of follicles in the ovaries and thickening of the uterine lining. This culminates in a surge of LH which causes ovulation of an egg. In the luteal phase, the corpus luteum forms and produces progesterone and estrogen to prepare the uterus for potential implantation. If implantation does not occur, hormone levels fall and menstruation begins, restarting the cycle.

1. The Menstrual Cycle www.freelivedoctor.com

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3. The Menstrual Cycle: Two Phases Ideally 14 days each Follicular and Luteal Describe changes in the ovary Proliferative and Secretory Describe changes in the endometrium www.freelivedoctor.com

4. Hormones in the Menstrual Cycle www.freelivedoctor.com

5. Follicular phase Begins with the onset of menses and ends on the day of the luteinizing hormone (LH) surge During late luteal phase/ early follicular phase: withdrawal of estrogen and progesterone in late luteal phase In early follicular phase, ovary is least hormonally active  low serum estradiol and progesterone release from negative feedback effects of estrogen + progesterone  increase in GnRH pulse frequency in early follicular phase Increased GnRH pulse  30% increase in serum FSH concentrations FSH release from the pituitary stimulates growth of 5-15 primordial follicles By late follicular phase, a single dominant follicle has been selected. www.freelivedoctor.com

6. Follicular Phase The developing dominant follicle produces estrogen in a 2-cell process Theca interna cells produce androstenedione in response to LH stimulation Granulosa cells convert androstenedione  estradiol when stimulated by FSH Estrogen causes the uterine lining to thicken / proliferate GnRH pulse frequency increase  rise in LH Rise in LH also stimulates androgen synthesis  androgens are converted to estrogens www.freelivedoctor.com

7. Follicular Phase Serum estradiol concentrations peak approximately 1 day before ovulation Midcycle (~day 14) there is an LH spike in response to this estrogen surge Ovulation occurs as increase in LH level causes the follicle to rupture and release mature ovum www.freelivedoctor.com

8. LH Surge Involves a poorly-understood neuroendocrine phenomenon in which there is a switch from negative feedback control of LH secretion by estradiol and progesterone to positive feedback Rising estradiol levels at the end of the follicular phase result in a 10-fold increase in serum LH concentration www.freelivedoctor.com

9. LH Surge: Effect on the Ovary In response to LH: Oocyte in the dominant follicle completes 1 st meiotic division Increase in local secretion of plasminogen activator and cytokines required for ovulation Oocyte released from follicle at ovarian surface ~ 36 hrs after LH surge. Even before oocyte is released, granulosa cells around it begin to “luteinize” and produce progesterone. Progesterone slows LH pulses/ decreases LH pulse frequency www.freelivedoctor.com

10. Ovulation LH spike stimulates ovulation, the release of the ovum from the follicle After ovulation, the luteal phase begins, and remnants of the follicle left behind in the ovary develop into the corpus luteum www.freelivedoctor.com

11. Ovulation Ovum usually passes into adjoining fallopian tube and is swept down to the uterus by the cilia lining the tube Takes 3-4 days for ovum to travel down tube to the uterus Fertilization must occur within 24 hrs of ovulation or ovum degenerates www.freelivedoctor.com

12. Luteal Phase After ovulation, granulosa and theca interna cells lining the wall of the follicle form the corpus luteum cyst (stimulated by LH) The corpus luteum synthesizes estrogen and large amounts of progesterone  Progesterone stimulates the endometrium to become more glandular/secretory in preparation for implantation of fertilized ovum www.freelivedoctor.com

13. Luteal Phase If fertilization occurs: developing trophoblast synthesizes human chorionic gonadotropin (hcg) hcg maintains the corpus luteum so it may continue producing estrogen and progesterone to support the endometrium By ~ 8-10 weeks gestation, the placenta is developed, and takes over production of estrogen and progesterone www.freelivedoctor.com

14. Luteal Phase If fertilization does not occur: corpus luteum is not maintained by hcg Corpus luteum degenerates after ~ 14 days Estrogen and progesterone levels fall Withdrawal of progesterone causes secretory endometrium to slough FSH levels slowly rise again in absence of negative feedback ↓ MENSTRUATION www.freelivedoctor.com