1 / 33

The Cycle

Mystery. Menstrual. The Cycle. Steven L. Young MD, PhD Obstetrics & Gynecology UNC School of Medicine. Mystery Cycle?. Don’t Panic!. Overall Objectives. Identify normal cycle characteristics Understand the physiologic function of the menstrual cycle.

dewitt
Download Presentation

The Cycle

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Mystery Menstrual The Cycle Steven L. Young MD, PhD Obstetrics & Gynecology UNC School of Medicine

  2. Mystery Cycle? Don’t Panic!

  3. Overall Objectives • Identify normal cycle characteristics • Understand the physiologic function of the menstrual cycle. • Review the structure, sites of production, action, and physiologic function of major reproductive hormones. • Understand how hormone action determines the menstrual cycle.

  4. Normal Cycle Characteristics Interval: 24-35 days (mean: 28 days) Duration: 2-7 days (mean: 5 days) Volume: Mean of 35 ml (> 80 ml abnormal) Composition: Nonclotting blood, endometrial debris, dead and living endometrial cells

  5. Menstrual Cycle Length 14 12 10 % INCIDENCE 8 6 4 2 40 22 24 26 28 30 32 34 36 38 DAYS

  6. 80 70 60 50 DAYS 40 Median Median Mean Mean 30 20 10 0 15 25 30 45 10 35 50 60 20 40 55 CHRONOLOGICAL AGE Menstrual Cycle Length:mean, median, 5th and 95th percentile by age

  7. Overall Objectives • Identify normal cycle characteristics • Understand the physiologic function of the menstrual cycle. • Review the structure, sites of production, action, and physiologic function of major reproductive hormones. • Understand how hormone action determines the menstrual cycle.

  8. Why a Menstrual Cycle? • Only seen in primates • Reproduction Monthly Fertility • Ovary Monthly Mono-Ovulation • Uterus Preparation for Embryo Implantation • Synchronization of Ovary & Uterus

  9. 2 6 8 12 16 20 22 10 14 18 24 26 28 4 Ovarian Cycle Ovulation Luteal Follicular CYCLE DAY

  10. 2 6 8 12 16 20 22 10 14 18 24 26 28 4 Endometrial Cycle Ovulation Secretory Proliferative CYCLE DAY

  11. 2 6 8 12 16 20 22 10 14 18 24 26 28 4 Synchronization Ovulation CYCLE DAY

  12. Overall Objectives • Identify normal cycle characteristics • Understand the physiologic function of the menstrual cycle. • Review the structure, sites of production, action, and physiologic function of major reproductive hormones. • Understand how hormone action determines the menstrual cycle.

  13. The Characters

  14. Testosterone & Inhibin Reproductive Endocrine Circuits hypothalamus hypothalamus GnRH GnRH pituitary pituitary Estradiol, Progesterone, & Inhibin FSH LH FSH LH Uterus & Breast Testis Prostate ovary sperm oocyte

  15. GnRH • Decapeptide that stimulates LH and FSH production • Released into portal blood vessels for direct action on pituitary. • Must be released in pulsatile fashion to stimulate LH and FSH synthesis and release.

  16. Hypothalamic-Pituitary Anatomy

  17. LH & FSH Production Require Pulsatile GnRH

  18. GonadotropinsFSH, LH, and hCG • Glycoprotein heterodimers Share same alpha subunit with each other and TSH. • Stimulate ovary FSH - folliclular development, estrogen LH - androgen, ovulation, progesterone • LH (and probably FSH) are released in pulses corresponding to GnRH pulses. • LH and hCG bind the LH receptor, but hCG has a much longer serum half-life.

  19. Steroids: Estradiol & Progesterone • Derived from C27 Cholesterol • Estradiol (C18) • Causes endometrial proliferation • Feeds back to pituitary (low levels supress LH release, high levels trigger LH release) • Induces female secondary sexual characteristics • Breast development, body fat distribution • Progesterone (C21) • Causes Endometrial Differentiation • Stops endometrial proliferation • Allows embryo implantation • High levels suppress pituitary FSH & LH

  20. CholesterolC27 DHEA-S Androstenedione Steroid Inter-conversion Pregneneolone 17-OH-Preg C21 C19 Progesterone 17-OH-Prog Estrone C18 Testosterone Estradiol Cortisol Aldosterone

  21. Inhibins • TGF-b family glycoprotein heterodimer produced primarily in ovarian granulosa cells (Inhibin B) and in luteal cells (Inhibin A) • Inhibits pituitary FSH secretion, also functions in ovary

  22. Testosterone hypothalamus (arcuate nucleus) - Pulsatile GnRH (portal vessels) + pituitary gonadotrophs - - FSH LH (+FSH) external genitalia, prostate + + Inhibin Sertoli Leydig Testosterone sperm Testis

  23. - Granulosa hypothalamus (arcuate nucleus) +/- Pulsatile GnRH + pituitary gonadotrophs - +/- FSH (+LH) LH Inhibin E2 + + Theca uterus Androgens oocyte

  24. Overall Objectives • Identify normal cycle characteristics • Understand the physiologic function of the menstrual cycle. • Review the structure, sites of production, action, and physiologic function of major reproductive hormones. • Understand how hormone action determines the menstrual cycle.

  25. Key Events in Cycle • Menstruation (shedding of endometrium) defined as day 1 • Proliferative or Follicular Phase • Ovulation (about d14.5 of cycle) • Secretory or Luteal Phase • Endometrium receptive for embryo implantation (d20-24 of cycle).

  26. Key Points: d1-5 of cycle Ovarian view = Early Follicular •  FSH drives Growth of a follicular cohort • Growing follicles:  FSHR, E2, & inhibin & vascularity of theca layer Uterine view = Menstrual / Early Proliferative •  E2 causes endometrial proliferation and hypertrophy (from 1mm single layer to 4-5 mm at ovulation). Pituitary View • FSH rises beginning a few days before d1 due to falling levels of inhibin A and P and E2 from failing corpus luteum

  27. Key Points: d5-13 of cycle Ovarian view = Late Follicular Phase. By day 5-7 falling FSH levels result in selection of the follicle most sensitive to FSH (dominant follicle). The dominant follicle produces increasing amounts of E2 and is destined to ovulate and while all other follicles become atretic. Uterine view = Proliferative Phase. Increasing E2 throughout the proliferative phase causes endometrial proliferation and hypertrophy (from 1mm single layer to about 4-5 mm). Pituitary View. As inhibin and E2 rise, FSH is decreased. At moderate E2 levels there is increased LH storage but inhibited release.

  28. Key Points: d14 (Ovulation) Ovarian view The dominant follicle has been able to make more and more E2 since acquiring increased FSH receptors and later LH receptors. A small amount of progesterone production stimulates a significant FSH surge which helps to further increase E2. In response to the LH surge, the oocyte is released and completes meiosis I. After ovulation the granulosa cells and some thecal cells form a corpus luteum which secretes E2 and P. Pituitary View. High E2 (>200 pg/mL) sustained over > 50 hrs causes massive release of LH.

  29. Key Points: d15-28 Ovarian view = Luteal phase. Corpus luteum has lifespan of 14 +/- 2 days unless rescued by logarithmic increases in hCG. CL produces E + P + inhibin. CL fails and increasing FSH recruits a new follicular cohort. Uterine view = Secretory. P causes a series of morphological and biochemical changes (differentiation) to allow the endometrium to become receptive to embryo implantation. Without pregnancy, P + E fall with CL atresia, resulting in sloughing of the functionalis layer of endometrium - menstruation. (day 1 of new cycle) Pituitary View. CL-derived E + P + inhibin suppress FSH production. As CL fails, FSH rises.

  30. Menstrual Cycle: menses to ovulation

  31. Ovarian Steroidogenesis:2 Cells, 2 Gonadotropins Early to Mid-Follicular B.M. Follicle Stroma FSH-R LH-R Theca Cell Granulosa Cell Estrogens Cholesterol Androgens

  32. Ovarian Steroidogenesis:2 Cells, 2 Gonadotropins Late Follicular through Ovulation B.M. Stroma Follicle LH-R FSH-R LH-R Theca Cell Granulosa Cell Estrogens + Progesterone Cholesterol Androgens Cholesterol

  33. Menstrual Cycle: ovulation to menses Not Pregnant Pregnant

More Related