Overview

1. Overview Dr.M.D.P.GoonaratneMBBS, FRCOG, SLCOG President Elect South Asian Federation of Menopause Societies

3. Menopause • Age • Life expectancy • Fall in ovarian follicular numbers • Estradiol • Inhibin A • Inhibin B • FSH • LH

7. FSH,E2, Inhibins During menopausal transition FSH E INH B INH A Dr. Sanjay Gupte

8. The postmenopausal ovary secretes androstenedione & testosterone. • After menopause androstenedione levels are reduced to one half; out of which most of it is from adrenals. • DHEA & DHEAS secreted by adrenals decline with age

10. Effects of Menopause • CNS • CVS • Bone • UGS • Hair/Fat/Breast

11. Menopausal symptoms Vaso motor hot flushes headache sweating CNS mood changes depression sleep disturbances irritability

12. Hot Flushes Sudden feeling of warmth Intense over face , neck and chest Lasts 30 secs to few mins- average 4 mins. Accompanied by sweating 15-20% severe enough to affect quality of life

13. HOT FLUSHES • 80% in perimenopause • 75% of post menopausal women; up to 5 yrs • 10-20% find them intolerable • in 20% Can persist up to 15 yrs • more abrupt & severe in surgical menopause

14. CHD • 3 - 4 fold Increase in women after menopause • Cardio protective Effect • Effects on Coronary vessels • Effects on Lipoproteins • Anti oxidant effects

15. Effects on Coronary Vessels • Increases NO synthase activity – vaso dilation • Ca antagonistic effect – smooth muscle relaxation • Ca activated K+channels opened • Inhibition of Endothelin-1 • Inhibits smooth muscle proliferation while stimulating proliferation of endothelial cells • Promotes angiogenesis • Alters the proportion of collagen and elastase in ECM

16. Effect of Menopause on Lipoproteins • Total cholesterol increase • LDL increase – small dense atherogenic • Lp(a) increase • TG increase • HDL reduced • HDL2 marked reduction • HDL3 slight increase

18. GUS vaginal atrophy dyspareunia loss of libido urinary incontinence Others loss of hair , thinning facial hair weight gain

19. HRT Menopause Estrogen deficiency Estrogen replacement

20. Conventional HRT • ET • EPT SERMS -agonistic and antagonistic effects Tibolone Phytoestrogens Testosterone

21. Estrogen • Oral - Conjugated equine estrogen - 17β estradiol • Transdermal • Intravaginal –tablets, creams, pessaries, rings • Subcutaneous implants • Nasal

22. Progesterone • 19 nor testesterone derivatives – NETA, Norgestrel • 17 alpha OH progesterone derivatives MPA Levonorgestrel • Oral • Transdermal • Creams, gels , pessaries • IUs • Dydrogesterone • Drospirenone

23. In general, progestogen should be added to systemic estrogen for all women with a uterus to prevent endometrial hyperplasia and cancer. Low-dose vaginal estrogens, administered for the relief of urogenital atrophy, are systemically absorbed, but not at levels that stimulate the endometrium, and so concurrent progestogen is not required. Progestogens, reason for use

24. Mirena (LNG IUS) 52 mg Levonorgestrel 20mcg/day 5 years (7 years bio-availability)

25. HRT Regimens • Continuous • Continuous combined • Cyclical sequential • Continuous sequential • Pulsed estrogen / pulsed progesterone

26. Benefits of HRT Vaso motor symptoms CHD Osteoporosis Urogenital system CNS

27. Synthetic SERMs • Raloxifene • Droloxifene • Lasofoxifene • Basodoxifene

28. Tibolone • Synthetic steroid, analog of Norethynodrel • Tissue specificity • 3 metabolites

29. Tibolone Active metabolites Receptor activation Sulfate inhibition Metabolism No active estrogenic componds 4 – isomer Bone Breast Endometrium (Brain, CVS, Vagina) Tissue stimulation Absence of Tissue stimulation Tissue – specific action of tibolone

30. Phytoestrogens Act like SERMS Isoflavones (Soya, lentils) genistein, daidzein Lignins (seed oils, cereals, fruits) enterodiol, enterolactone Coumestans (bean sprouts, sunflower seeds, red clover)