2. (PROBABLY MORE THAN) EVERYTHING YOU WANTED TO KNOW! July 7, 2015

4.  ENVIRONMENTAL FACTORS stress exercise weight nutrition  HYPOTHALAMUS (neuroendocrine) gonadotropin releasing hormone (GnRH)  PITUITARY GLAND follicle stimulating hormone (FSH) luteinizing hormone (LH)  OVARY estrogen, progesterone, androgen

9. www.pbs.org/wgbh/amex/pill/sfeature/sf_cycle.swf

10.  Primary follicle  granulosa cells  theca cells  antrum FOLLICLE

11. GRAAFIAN FOLLICLE

12. OVULATION

13. CORPUS LUTEUM

14. Maturation of the Hypothalamic-Pituitary-Axis: 1. Pulsatile Gonadotropin releasing hormone 2. Development of Positive Feedback (estrogen)

15. 2. Development of positive feedback A. Prior to puberty: negative feedback only : EstrogenCausing LH B. After puberty, also have positive feedback Estrogen Causing LH

16. WHAT HAPPENS IF YOU BLOCK THE

18. Painful menses (cramps, diarrhea) Prostaglandins: cause smooth muscle contractions 1. Increased levels in dysmenorrhea 2. Higher levels in ovulatory cycles 3. Higher levels in secretory phase Treatment 1. Prostaglandin inhibitors: ibuprofen 2. Birth control pills

19. When: week preceding until 1st few days of menses Why: change in hormone levels or predisposition: abnormal response to normal hormone changes What: tension, irritability, mood swings, anxiety, headaches, dysphoria, breast tenderness Severe PMS: premenstrual dysphoric disorder (DSM 4) Severe dysphoria/depression 2-10% of women Treatment Medical: SSRIs (e.g. prozac), calcium, Vit B 6, alprazolam, Birth control pills

20.  Conflicting studies  Role of pheromones: influence biology & behavior  Underarm pheromones: early follicular: shortens mid-cycle: lengthens luteal: no change  Why: 1)group mothering 2)puberty onset

21. No further estrogen: What happens to FSH levels? Symptoms: hot flashes vaginal dryness osteoporosis 1960s: feminine forever: estrogen 1970s: HRT (Est & Prog) WHI: Women’s Health Initiative (2001) HRT: breast cancer, heart disease, strokes Today: estrogen if symptomatic up to 5 years

22. SEX HORMONES, SOUNDS SEXY!!! ONLY IF YOU’RE INTO CHOLESTEROL

24. HOW IS ESTROGEN MADE?

25. My ovaries make estrogen! How do I break the news to her they also are androgen factories?

26. OVARY: ESTROGEN & ANDROGEN PRODUCTION

28. Clinical Features:Androgen excess: acne, hirsutism Anovulation: menstrual disturbance (amenorrhea, oligomenorrhea, DUB Diagnosis: Clinical history Hirsutism Increased androgens Endrocrine Abnormalities: Increased LH (abnormal estrogen secretion) Increased androgens (testosterone; androstendione) Estrogen secretion (no preovulatory increase; non- cyclical production of estrone from androgens) Pathogenesis: Ovarian dysfunction: dysregulation of enzyme in androgen synthesis in theca cells; role of insulin

29. Figure 5. Gross and cut appearance of typical polycystic ovaries. Multiple small follicular cysts are apparent in the cut section.

30. OVARY: ESTROGEN & ANDROGEN PRODUCTION

31. Since you seem to know so much, what do I do: I haven’t had a period in months. Of course I know a lot; I took Women’s Medical Issues! I think you have ___ but go to Health Services to be sure.

32. Jane is a 19 year old sophomore. She comes to Health Services in September concerned because she has not had a period since June. What information do you want to know about Jane?

33. Michelle is a 19 year old sophomore. She comes to Health Services in September because she has not had a period since July. Michelle always uses condoms with her boyfriend. Her cycles are pretty regular although occasionally she skips one. She runs for 30 minutes several times a week. While Michelle wishes she was thinner, she is not trying to lose any weight at present. Her summer was pretty stressful at home and she’s quite happy to be back at Wilder. What information to you want to gather on physical? What laboratory tests do you do?

34. Rachel is a 20 year old junior who presents to Health Services with no menses in the last 4 months. Her weight has fluctuated up and down 5 pounds at most and she exercises a couple days a week. Rachel is sexually active only with her girlfriend. She does not have acne and has not noticed any growth of facial hair. The only stress she has in her life is worrying about her period since she is usually regular. Her physical examination is normal, including weight for height. What laboratory tests would you do?

35. Rachels’s FSH level is very high. What does that mean? What is likely to happen if she is given progesterone to induce a period and why?

36. CASE 4 HISTORY: Last period 3 months ago Not sexually active Lots of exercise because has gained weight Upset because of hair on chin & acne Physical Exam: Overweight (weight for height) Acne on face, chest, back; hair on chin

37. SEX HORMONES July 7, 2015 “If Shakespeare had been a chemist, he would have loved estrogen, a hormone fit for comedy, tragedy and a sonnet or two”. Natalie Angier New York Times

38. Menopause cessation of estrogen  What happens to FSH?  Symptoms: hot flashes vaginal dryness (osteoporosis)  Treatment: estrogen but estrogen increases breast ca heart disease uterine cancer

39.  BRAIN: memory; prevents Alzheimers?  BREASTS: causes cancer  BONES: prevents osteoporosis  LIVER: improves lipids; causes blood clots  UTERUS: causes cancer  VASCULATURE: prevents heart disease by: 1)dilates vessels 2) prevents plaques 3)lipids

40.  2 RECEPTOR SITES FOR ESTROGENS  ONE SITE ACTIVATES WORK OF ESTROGEN (agonist)  ONE SITE BLOCKS WORK OF ESTROGEN (antagonist)  DESIGNER ESTROGENS TAKE ADVANTAGE OF DIFFERENT RECEPTORS: TAMOXIFEN (NOLVADEX) RALOXIFENE (EVISTA)

41. TAMOXIFEN  PREVENTS BREAST CA  CAUSES UTERUS CA  PREVENTS OSTEOPOR  HARMS LIPIDS  CAUSES HOT FLASHES  RISK OF CLOTS RALOXIFENE  PREVENTS BREAST CA  PREVENTS UTERUS CA  PREVENTS OSTEOPOR  IMPROVES LIPIDS  CAUSES HOT FLASHES  RISK OF CLOTS

43. India: birth control since 1990s legal since 2009 Weekly pill: 98 to 99 % effective Desynchronizes: ovulation and endometrium Anti-estrogen for breast and uterus Why not used in US?

44. ANY CELL WITH AROMATASE CAN MAKE ESTROGEN FROM ANDROGEN. FAT CELLS CONTAIN AROMATASE Heavier women have decreased risk of osteoporosis Heavier women may have irregular menstrual cycles Heavier post-menopausal women make more estrogen Obesity increases the risk of breast cancer By interfering with normal positive & negative feedback

45.  Synergistic with LH to increase androgen production of theca cells  Decreases liver production of sex hormone- binding globulin (increasing the biologically active free testosterone).

46.  Obesity (BMI >30: Kg/m2): diet, exercise  Menstrual irregularity: OCP (84 day cycles), cyclic progesterone, insulin sensitizers (metformin: contra-indicated with alcohol)  Hirsutism: OCP, anti-androgens spironalactone 50-100mg BID, mechanical treatments)

47. Pink viagara: dyspareunia in menopausal women vaginal dryness ‘only non-estrogen’ available for vaginal dryness Causes: hot flashes, blood clots unstudied re breast cancer