Endocrinology of the Female Reproductive Axis

Transcription

1 Endocrinology of the Female Reproductive Axis girlontheriver.com Geralyn Lambert-Messerlian, PhD, FACB Professor Women and Infants Hospital Alpert Medical School at Brown University Women & Infants BROWN

2 Learning objectives 1. Diagram the main components of the female reproductive axis 2. Describe basic immunoassay methods for measurement of reproductive hormones 3. List the primary hormones secreted in pregnancy

3 Overview of the female reproductive axis Gonadotropin releasing hormone Gonadotropin hormones Follicle stimulating hormone Luteinizing hormone (Gonad) Inhibin Modified from Hiller-Sturmhöfel and Bartke, Alcohol Health & Research World, 1998

4 Ovarian Physiology FSH Kaipia & Hsueh, Ann Rev Physiol, 1997

5 Normal menstrual cycle FOLLICULAR PHASE Day 1 FSH Thorneycroft, Am J Obstet Gynecol, 1971

6 Developing ovarian follicle GRANULOSA CELL THECA CELL ANTRUM Sherwood, Fundamentals of Physiology, 1991.

7 Steroid biosynthesis in ovarian follicles Granulosa cell Theca cell Griffin and Ojeda, Textbook of Endocrine Physiology, 2004

8 Estradiol Follicular phase of the menstrual cycle

9 Inhibin B Inhibin B is secreted during the follicular phase of the menstrual cycle FSH Estradiol Groome et al, JCEM;1996

10 Feedback regulation of the menstrual cycle Fauci et al. Harrison s Principles of Internal Medicine, 17 th edition

11 Mid-cycle LH FSH Estradiol

12 Ovulatory LH surge Development of the corpus luteum Sherwood, Fundamentals of Physiology, 1991.

13 Steroid biosynthesis in corpus luteum

14 Luteal phase of the menstrual cycle LUTEAL PHASE Progesterone Estradiol

15 Menstrual Cycle Summary Sherwood, Fundamentals of Physiology, 1991.

16 Inhibin A is secreted by the corpus luteum Inhibin A Groome et al, 1996; JCEM

17 Immunometric (sandwich) assay Y Y Y Y Amount of signal Sample or standard concentration FSH FSH Y Y Y Y Y Y ANTIBODY

18 Competitive immunoassay Exogenously added, labelled hormone % Binding of radioactivity Sample or standard concentration Y Y Y Endogenous hormone in the sample ANTIBODY

19 Sample reference data Menstrual cycle Follicular Ovulatory Luteal Menopause FSH (miu/ml) LH (miu/ml) < Estradiol (pg/ml) X 3.67 = pmol/l Progesterone (ng/ml) X 3.18 = nmol/l < < 30 < < Inhibin A (pg/ml) < 10 Inhibin B (pg/ml) < 16 Women and Infants Hospital

20 Hormone monitoring for fertility treatment 37 year old woman with history of infertility History of irregular menstrual cycles and infertility Normal anatomy Treated with high dose exogenous FSH to stimulate ovaries Serial estradiol levels (pg/ml) Day Day Day Day 7 1,272 What do these results indicate? Does this woman have a good chance of pregnancy success?

21 Hormone monitoring for fertility treatment 37 year old woman with history of infertility History of irregular menstrual cycles and infertility Normal anatomy Treated with high dose exogenous FSH to stimulate ovaries Serial estradiol levels (pg/ml) Day Day Day Day 7 1,272 What do these results indicate? About follicles have developed Does this woman have a good chance of pregnancy success? YES!

22 Hormones in Pregnancy Fetal-placental unit

23 Placental hormones Human chorionic gonadotropin Estradiol Progesterone

24 Sample reference data hcg in pregnancy Weeks from hcg (miu/ml) conception , ,000-20, , ,000 2 nd trimester 20,000-60,000 3 rd trimester ,000 Women and Infants Hospital

25 Monitoring pregnancy viability 30 year old woman Pregnant by home urine test Presents with some vaginal bleeding at ER Gestational age estimate = 4 weeks Serial hcg (miu/ml) Day 1 3,000 Day 2 4,720 Day 3 7,590 Is this a viable pregnancy?

26 Monitoring pregnancy viability 30 year old woman Pregnant by home urine test Presents with some vaginal bleeding at ER Gestational age estimate = 4 weeks Serial hcg (miu/ml) Day 1 3,000 Day 2 4,720 Day 3 7,590 Is this a viable pregnancy? YES! hcg should rise by a minimum of 53% every 48 hours in early pregnancy Barnhart et al., Obstet Gynecol, 2004

27 Progesterone in pregnancy ng/ml Yen and Jaffe, Reproductive Endocrinology, 1991

28 Estrogens in pregnancy Gabbe, Niebyl and Simpson, Obstetrics, 1991.

29 Estriol synthesis in pregnancy Estradiol Estrone Sulfatase Aromatase

30 Summary Female reproductive hormones annsrunningcommentary.com Vary with menstrual cycle day, pregnancy and menopause Require samples timed to cycle day and clinical information for proper interpretation Are useful tools to evaluate fertility and pregnancy health