Drugs that affect gonadal hormones

1. Drugs that affect gonadal hormones

2. Refresh your memory Female Gonadal hormones

3. Ovarian hormones • Estrogen • Progesterone • Small amounts of androgens • Testesterone(<200mcg \d) • Androstenedione • Converted to testosterone and estrone in peripheral • Function: • Normal hair growth • Female libido • Metabolic effects • inhibin • Inhibit FSH secretion • Activin • Increase FSH secretion • Relaxin • Decrease uterine contraction • Increase glycogen synthesis

4. Organ system effects f estrogen

5. Also estrogen elevate the levels of :thyroxine,iron copper why?

6. Clinical uses of estrogen • Primary hypogonadism • Postmenopausal hormonal therapy • Contraception • Hairsutism

8. Contraindications

9. Organ system effects of progesterone

10. Also progesterone is responsible for alveolobular production in the breast Maturation and secretory changes of the endometrium Increase the ventilatory response to PCO2

11. Clinical uses • Contraception • Hormonal replacement therapy • Premenstrual syndrome • Diagnostic test: • Test the estrogen secretion • Progesterone 150mg\d or medroxyprogesterone 10mg\day is given for 5-7 days ,this regimen will be followed by bleeding in amenorrheic pts only when the endometrium is stimulated by estrogens

14. Refresh your memory Menstrual cycle

20. Female contraceptionbefore conception • Pills or implants or IM injection are taken to prevent conception • Combined or mini pills

21. 1-Combined pills • Contain estrogen or its derivatives and progesterone or its derivatives • According to progesterone concentration in the pills we divide the combined pills to 3 subtypes: • Monophasic • Biphasic • Triphasic

23. Preparations available • Orally • Transdermal • Vaginal ring

24. The main advantage of bi and tri phasic administration • Decrease the progesterone administration • Thus decrease the SE’s

26. Estrogen Mechanism of action as contraceptive • Estrogen=proliferative agents

28. Progesterone mechanism of action as contraceptive • Inhibit ovulation 70-80% • Alteration in gonadotropin pulsing • Decrease pituitary gland response to GnRH • Alter cervical mucosa • Increase endometrial secretion • Decrease peristalsis The zygote unable to implant

29. Side effects and C\I of progesterones • Increase the risk of osteoporosis • Increase risk of atherosclerosis • wt gain • Decrease in glucose tolerance

30. How to administer the combined pills? • Take it daily for 21 days then 7 days free why? • To resemble the normal menstrual cycle

31. Benefits • Decrease ovarian cancer • Decrease the endometrial cancer • Estrogen only products increase the risk of endometrial cancer why?

32. Side effects of long term use of OC’s • DVT • PE • Studies fail to approve the increased risk of breast cancer • Gall bladder disease

33. Do OC’s cause infertility ? • Chronic use depresses ovarian function • Ovaries become smaller • Majority of pts return to normal menstrual patterns when the drug is discontinued • 75% will ovulate in the first posttreatment cycle • 97% will ovulate by the 3rdposttreatment cycle • About 2% remain amenorrheic for periods up to several yrs

34. 2- Minipills • Contain only progesterone or its derivatives • Norgestrel and norethindrone are the most widely used progesterone • Minipills must be used continuously without free intervals like combined pills • Used in women when: • Estrogen is not desiered or C\I • Lactating women bec. Estrogen suppress the lactation • Lactating women seeking contraception

35. Emergency Contraception • Plan B / Morning After Pill • 0.75 mg levonorgestrel X 2 - within 5 days of unprotected sex • Mechanism: • Inhibit LH surge • Thickens cervical mucus • Possible interference with fertilization or implantation • WILL NOT HARM AN ESTABLISHED PREGNANCY!!! • Now OTC!!!

36. Medical Abortion • Mifepristone / RU-486 • Inhibits progesterone receptors causing disruption at implantation site or • Methotrexate • Inhibits dihydrofolatereductase (stops rapidly dividing cells) • Used with misoprostil • Prostaglandin analog produces uterine contractions • Cheap, common medication also used for: arthritis, ulcers, constipation, cervical ripening

37. Preparation available • Oral tablet • Implants • Norgestrel implant • Intramuscular injection • Medroxyprogesterone • Vaginal rings • Hormonal Intrauterine devices

38. Day after contraception • Taken after unprotective sexual intercoarse • Exact mechanism of action unknown may be: • Inhibit ovulation • Inhibit transport of fertilized egg • Efficacy 75-80%when taken within 72 hr after fertilization • 3 approaches : • High dose of estrogen and progesterone • Estrogen only • Must be combined with antiemetic drug • Mifeproston +misoprostol

39. Mifeproston • Progesterone receptor antagonist • Also it is aglucocorticoid antagonist • Used as an abortifacient in the first two months of pregnancy • In smaller doses as an emergency contraceptive • Given along with misoprostol once within 72 hr from unprotective coitus

40. Male contraception • The identical agent is • Decrease the spermatogenesis • Difficult to reach bec. Inhibition of 99% of sperms would result in enough sperms for fertilization • No erectile dysfunction • No decrease in libido

41. Mechanism of action of both testosterone and progesterone in male contraception

43. Hormonal antagonist • We have talked about progesterone agonist and cyproterone • Now ,we will talk about Selective estrogen receptor modulators SERM

45. Mechanism of action

47. SERMs uses

48. SERMs special considerations