Menopause Hormone Therapy and Contraception

1. Menopause Hormone Therapy and Contraception Iwona Jagielska

2. Menopause • Permanent cessation of menstruation resulting from the loss of ovarian follicular activity • Natural menopause is recognized to have occured after 12 consecutive months of amenorrhea, for which there is no other obvious pathological or physiological cause • Menopause occurs with the final menstrual period (FMP) which is known with certainty only in retrospect a year or more after the event • Typically occurs between 45 and 55 years of age • An adequate biological marker for the event does not exist!

3. Menopause- the meaning • 1/3 of a woman’s life occurs in postmenopausal • 2/3 of women suffer from menopausal symptoms • in 40 % of women over 60 years old are fractures • Annual spending on treatment of osteoporosis and its consequences exceed $ 10 billion worldwide • 50 % of women die of cardiovascular disease

4. The aging of the ovaries • Reducing the production of inhibin • Increase secretion of E2 and FSH ↓ in the early follicular phase • Shortening the follicular phase • Premature ↑ concentrations of P and progressive luteal insufficiency • LH peak earlier • ↓ quantity and quality of oocytes • The decrease in proliferation and apoptosis enhancement • Abnormal nuclear and cytoplasmic maturation of the oocyte

5. Clinical division of menopause 50 rż 65 rż 35 rż premenopause postmenopause senility perimenopause • 35 years of age—50.-----------65 years of age

6. Premenopause •  The term premenopause is often used ambiguously to refer to the one or two years immediately before the menopause or to refer to the whole of the reproductive period prior to the menopause. The group recommended that the term be used consistently in the latter sense to encompass the entire reproductive period up to the FMP. [Source: WHO] • Progressive reduction of the secretion of steroids , particularly progesterone , and 17 - β - estradiol which is associated with impaired maturation of the follicles • It follows luteal failure responsible for the reduction of the secretory phase of the cycle and the severity of premenstrual symptoms

7. Menopause hormone • FSH> 20 U/l ( 10-20-30 x )‏ • E2<20 pg/ml • FSH/LH>1 LH 4 – 8 x The highest concentrations of FSH and LH achieve in 2-3 years after menopause

8. Estradiol postmenopausal • The rapid decrease in concentration to 13 pg/ ml • Source: ovary and testosterone and androstenedione ( slightly) in the aromatization extraglandular

9. Androgens postmenopausal • The main androgen in postmenopausal women ANDROSTENDIONE D4 • The concentration is reduced to the level observed after castration • The main source of postmenopausal: • adrenal cortex TESTOSTERONE • The concentration decreases approx. 1.3 , with a decrease in daily production 25% compared with the period of childbearing • After menopause, the ovaries make up approx. 50 % of the total pool of testosterone ( premenopausal approx. 25%)

10. Age of menopause • USA 54.1 years • Italy 50.9 years • Netherlands 49.5 years • Poland 49.7 years

11. Factors delaying menopause • Many children • Drinking small amounts of low-percentage alcohol • Vegetarian diet • Combined contraceptive pills

12. Climacteric syndrome • The climacteric is sometimes, but not necessarily always, associated with symptomatology. When this occurs, it may be termed the "climacteric syndrome." [Source: IMS] • „Neurovegetative and psycho- syndrome occurring during menopause underpinned by changes in the hormones and neurotransmitters level and probabely also changes of the blood supply to the different areas of the brain” (Sherman BM et al. 1979)

13. Menopausal hormone therapy Estrogenes ( estradiol, estriol, conjugated estrogenes) Gestagenes Androgenes

14. Types of Menopausal Hormone therapy (HT) 1.Estrogen therapy  -most highly effective prescription medication for treating menopause symptoms and in light of recent research is still safe and effective for many women when used for fewer than five years -exclusively for women after hysterectomy! -associated with an increase in the risk of uterine cancer (endometrial cancer, cancer of the lining of the uterus). 2. Combination estrogen /progesterone treatment -Treatment with progesterone along with estrogen substantially reduces the risk of uterine cancer(endometrial cancer) so that the risk of developing this cancer is equivalent to that of women not taking estrogen.

15. Individualization of therapy by selecting : • Route of administration -percutaneously -orally -intramuscularly • vaginally • sublingually • Regimen (continous, phase) • Dose • Type of preparation • The start and the time scale of conduct • Type of examinations • Frequency of visits at the gynecologists

16. Menopausal hormone therapy- route of administration • 1.Oral • 2. Percutaneus (patches, gel) • 3.Intramuscular injections • 4.Transdermal • 5.Subcutaneous implants • 6.Vaginal • 7.Nasal • 8.IUDs

17. Percutaneous way-in case of • 1. Diseases of the biliary tract and gastrointestinal tract • 2. A significant degree of obesity • 3.Hypertension • 4. Hypertension • 5.Hypothyroidism • 6. Smoking • 7. Hypertriglyceridemia

18. The oral route of administration • 1.Affects the levels of : cholesterol , HDL, LDL , VLDL • 2.Cardioprotective effect • 3. Comfortable application • 4.Patient acceptance

19. Dosage • Starting with a low dose To increase only when needed • Low dose:<=1mgE2/24h p.o. • <=25mcg/24h

20. Type of hormone therapy in premenopause • -Progestagene in the second stage of the cycle • -MHT (there are problems vasomotor) • -Oral contraception ( if needed)

21. Type of therapy • 1. Sequential therapy: premenopause, perimenopause • 2. Continous therapy: year after menopause- no later than 55- 56 years of age • With FSH: > 30 IU/l and E2< 30 pg/ ml

22. Ideal progestin • -strong affinity for PR • -lack of estrogenic activity • -lack of androgenic activity • -lack of mineralo -/ glucocorticoid activity • -antimineralocorticoid activity • -the best: natural progesterone

23. Ideal MHt • 1.Prevents endometrial hyperplasia • - by causing regular bleeding • - by causing athrophy • 2. Normalizes bone turn- over • - prevents osteoporosis • -shows no negative effect on the lipid profile • (prevention of ischemic heart disease)

24. Contraindications to MHT • 1.undiagnosed vaginal bleeding • 2.active liver disease • 3. arterial embolic disease - thrombotic ( heart attack ) • 4.venous thromboembolism • 5.hormone-dependent tumors ( breast cancer, endometrial cancer, ovarian cancer, melanoma, meningioma) • 6. untreated hypertension • 7.late-onset cutaneous porphyria

25. Significance MHT in the treatment of osteoporosis • 1.reducing osteoclasts activity • 2. preventing rapid loss of bone density in postmenopausal women 80-90 % • 3. reducing the risk of bones fractures by 50 % • 4. smaller percentage of fractures of the hip and spine • 5. preventing decrease of growth

26. MHT and nervous system • 1. effects on brain function of the amount , morphology and function of the neurons • 2. effect on neurotransmitters • 3.effect on gial cells • 4. effect on the protein present in Alzheimer's disease\ • 5. effect on the cognition • 6. effect on mood and behavior • 7. Alzheimer’s disease • 8.Parkinson’s disease

27. Reasons for the increase of survival of women diagnosed with breast cancer and • 1. breast cancer recognized in the early stage • 2.women using MHT= „healthy user effect” • 3. MHT could initiate the growth of already existing hormone-dependent tumors • 4. HRT may lead to slower-growing tumor growth and / or inhibit the growth of tumors, particularly invasive

28. Recommendations of the Polish society of gynecologists to use MHT • The discomfort of menopause • Atrophic changes in the system, the genitourinary system, • Prevention of osteoporosis postmenopauzalnej and its treatment • Premature menopause - HRT - before reaching the average age for menopause is approx.. 51years

29. Diagnostic tests required prior to initiation of therapy • 1. General medical examination • 2. Gynecological examination • 3. PAP test • 4. Mammary glands examination • 5.Mammography • 6. Transvaginal ultrasound • 7.Hormone laboratory tests • 8.Densitometry

30. MHT- monitoring • 1. The first medical examination after 2 - 3 months • 2. Then every 6-12 months • 3. Additionally, in the event of abnormal bleeding • 4.The area of examinations: • - every year: mammography/breast ultrasound • gynecological examination • PAP test every year/ every second year • -in some cases: hormones, lipid profile

31. MHT • 1. Not for every woman!! • 2. The need for individualization of therapy • 3. Therapy of low-dose , short-term • 4.Monitoring

32. Contraception

33. Contraception- methods 1.Natural methods 2.Barrier methods 3.Intrauterine 4.Vaginal 5.Hormonal DHA oral contraception (OC) Transdermal Vaginal ring IUD ( intra uterine device) The Implant ( intradermal) „The Shot” (intramuscular) Postcoital contraception

34. Natural methods • 1. Abstinence • 2. Basal Body Temperature (ovulation raises body temp and temperaturę will drop if fertilization does not occur) • 3. Evaluation of vaginal discharge and mucus • 4. Withdrawal/ Pullout

35. Natural methods • Advantages • Disadvantages • total reversibility • understanding your body • high security • Low efficiency • Comparable to Placebo • Decreased libido ( due to stress)

36. Barrier methods • Male condom • Female Condom • Diaphragm (a soft, silicone dome that covers the cervix) • Cervical cup ( a soft, silicone cup holding spermicide designet to fit over the cervix) • Spermicides (chemicals that go to the vagina before sex, most work for 1 hour)

37. Condomes • Advantages • Disadvantages • reduces the risk of transmission of sexually transmitted diseases • safe • Low efficiency

38. Intrauterine devices (IUDs) • Copper • Hormonal • Over 99% effective • T shaped plastic that releases progestin-levonorgestrel locally into the uterus • thickening cervical mucus to prevent sperm from entering your uterus • • Inhibiting sperm from reaching or fertilizing your egg • • Thinning the lining of your uterus • Mirena( for 5- years)/ Jaydess (for 3-years) • Causes a local inflamation • 10 years • 99.2 % effective • Copper on IUD acts as spermicide, IUD blocks egg from implanting

39. Mirena/ Jaydess • The most effective form of birth controll • Long – term effect • Local activity • Does not impair libido • No effect on the increased risk of thromboembolic • Quick reversibility (ovaries still run) • Decrease the risk of endometrial hyperplasia • Disadvantages: - price, often-functional cysts, discomfort during installation • Jaydess( especially for nulliparous women and with small cervix)

40. Vaginal Devices- NuvaRing(etonogestrel/ethinyl estradiol vaginal ring) • A small, flexible vaginal ring ( should be introduced for 3 weeks and then replaced with a new) • Does not require a „fitting” by a health care provider • 99%effective • Ability to become pregnant returns quickly when use is stopped • Libido decreases less than OC • NuvaRing is absorbed through the portal circulation system in the vagina

41. NuvaRing-disadvantages • Increases blood clotting • „In some studies of women who used NuvaRing, the risk of getting a blood clot was similar to the risk in women who used combination birth control pills. • Other studies have reported that the risk of blood clots was higher for women who use combination birth control pills containing desogestrel (a progestin similar to the progestin in NuvaRing) than for women who use combination birth control pills that do not contain desogestrel” • Increases frequent vaginitis • Symptoms (head aches)- as the OC • Women with pelvic organ prolapse-may fall out of the vagina ( if this happens, it can be washed and within 3 hours re-inserted into the vagina)

42. OC:Single- dose pill- „Mini pill” • Contains only desogestrel in a low dosage • It should be taken continously • No bleeding • Influence on endometrium ( decidualisation)- no ovulation • Low risk of blood clotts • Used by breast- feeding women • Recommended in women with varicose veins , smoking (more than 15 cigarettes) and hypertension • Disadvantages: tendencies to to depression severity, lowers libido

43. OC- Two component pill(estrogen + progestinI-/II-/III- generation • The lower dose of ethynyl-estradiol , the lower the risk of venous thromboembolism, and a higher risk of vaginal spotting • Antiandrogenic • Drug selection depends on many factors such as heavy bleeding or acne etc…

44. Dosing regimens 21+7 ( 7 –day break) 24+4 ( continously)- 21+ 7 continously( 7 placebo pills) 26+2: over 40. years old; with strong bleeding

45. Three-phase contraception pills • binary but comprise three variants concentrations for taking 21+ 7 • assumption: imitate an ovarian cycle • rarely used , because of increased dosage of hormones • therefore mainly used to eliminate heavy bleedings

46. Transdermal Patches • 21 +7 • 3 patches- changed weekly, no patch on 4th week • Upper outer arm/ upper torso 9 excluding breasts), buttock, abdomen • For unsystematic women • < 80 kg • lack of first-pass metabolism • Disadvantages: allergic reactions, possibility of peeling the patch • Advantages: women on diet- slimming drinks can cause difficulties with absorbing the pills

47. Depo Provera(medroxyprogesterone acetate) • 1x/ 3 months (intramuscularis) • For breast feeding women • into the woman's arm or buttocks • Disadvantages: gaining on weight after long term using decreases libido, depression, bad invertable,

48. Subdermal Implant- Norplant • Little cut on the shoulder • Effective for up to three years • Rapid return of fertility • Consists of 6 capsules implanted under the skin of the upper arm • Disadvantages: waight gain, menstrual irregularity, surgical implantation and removal

49. Postcoital contraception • Hormonal methods: Estrogenes, OC, Danazole,Ru 486The mechanism of action depends on the time of application: 1 phase of the cycle- suppression of ovulation, phase 2- impact on the endometrium, !can not cause the interruption of the current pregnancy! • Mechanical methods: IUD

50. Postcoital contraception • EllaOne: contraceptive pill containing 30 mg of ulipristal acetate, a progesterone receptor modulator. It is effective for up to 5 days after unprotected sex • Escapelle :prevents a pregnancy before it is established by preventing or delaying the release of an egg from the ovary (by preventing ovulation) with the help of a hormone called Levonorgestrelprevents a pregnancy before it is established by preventing or delaying the release of an egg from the ovary (by preventing ovulation) with the help of a hormone called Levonorgestrel, the same hormone found in many regular contraceptives. It doesn't work if you are already pregnant and will not harm an already established pregnancy. The sooner you take Escapelle, the more effective it is • Postinor: levonorgestrel: the tablet should be taken no later than 72 hours after intercourse.