CLIMACTERIC

1. CLIMACTERIC By: Dr. Nisma Mansouri Assistant Professor Consultant OB & Gynae

2. Content: • Introduction. • Definitions. • Perimenopausal transition: • Age. • Symptoms. • Hormonal changes. • Management. • Treatment. • Menopause: • Age • Hormone production after menopause. • Symptoms of menopause. • Long term issue. • Osteoporosis: • Sign and symptoms. • Diagnostic test • Deferential diagnosis • Hormone replacement therapy (HRT): • Risks • Benefit.

3. CLIMACTERIC • Introduction● To day, life expectancy to reach age 81 years in man and age 84.4 years in woman● Women spend > ⅓ of their lives in the postmenopausal years.● People should live relatively healthy life and compress or prevent our illnesses in to a short period of time.● By health care include family planning cessation of smoking, control of body weight, prevention of cardio vascular disease and osteoporosis, maintenance of mental well – being , cancer screening and treatment of urologic problems.● It is important to all physicians and patients to understand the emotional and physical consequences of decline in ovarian hormones at the short and long term.

4. Definition of the Climacteric: It is an older, more general, and less precise term, indicates the period of time when a women passes from the reproductive stage of life through the perimenopausal transition and the menopause to the postmenopausal years. • Climacteric is not an endocrinopathy but a normal consequence of the aging process.

5. Definitions: The stages of Reproductive Aging workshop was held in 2001. It provides useful clinical definitions of the menopausal transition, perimenopause, menopause and post menopause:

6. Menopausal Transition: Begins with variation in menstrual cycle length and an elevated serum FSH Concentration and ends with the final menstrual period (dived stage – 2 (early) is c.c.c by variable cycle length & stage – 1 (late) is c.c.c by prolonged interral of amenorrhea >, 60 days, +ve hot flashes..

7. Perimenopause: Around the menopause that begins in stage – 2 of the menopausal transition and ends 12 months after the last menstrual period.

8. Menopause: Greak wards Men (month) & pauses (cessation) cessation of period fallowing the loss of ovarian activity and absence of ovarian estrogen secretion. (begin after 12 month of Amenorrhea after the final period. Menopause occures when the number of remaining follicles falls below a critical threshold about 1000 regardless of age.

9. Post menopause: Stage + 1 (early) first 5 years after the final menstrual period cc.c by accelerate bone loss and not flushes. Stage + 2 (late) after 5 years to death.

10. PERIMENOPAUSAL TRANSITION: • Most important period to provide education and prevent and detect chronic diseases including hypertension, heart disease, D.M. and cancer. • Important symptom is disturbance in menstrual pattern (irregularity of period change in length of cycle). Including anovulation and reduced fertility then Amenorrhea

11. Perimenopausal transition : The duration of the follicular phase is the major determinate of the cycle length. Average age of onset 46 . Age of onset 95% of women 39 to 51. Average duration 5 years . Duration for 95% g women 2 – 8 y.

12. Hormone change in perimenopousal transition: • FSH Markel elevated. • inhibin decrease level, (↓ follicular no) • LH normal level • Slightly elevated levels of estradiol.

13. Management of perimenopausal transition: Main problem chronic anovulation and progesterone deficiency may lead to long periods of unopposed estrogen exposure and therefore anovulatory bleeding and endometrial hyperplasia (un complicated by atypia) I. Bleeding : DUB (prolifrative or hyperplasia with out atypia) (history, Examination, investigation → a. Uls pelvis → endometrial thickus > 5mm → ovarian mass. b. Pap smear c. Endometrial biopsy → plastic endometrial suction device → D&C sp – abnormal big irregular Utrus

14. Trestment: • Low – dose oral contraceptive. • Intermittent progestine therapy → oral proster 5 – 10 mg ld first 14 days of each month then fallow up biopsy. II.Hyper plasia with atypia → hysterectomy.

15. MENOPAUSE • The average age 51 + 5 years . • 5% of women after 55 years . • 5% of women between 40 – 45 years . • 10% < < become menopause by age 45 y . • Menopause occurring prior for age 40 years in considered to be premature ovarian failure.

16. Earlier onset of menopause associated with: • Smoking, (no. & duration) . 2. Genetic variation. (family history of early menopause . 3. Nuliparous . 4. High altitudes . 5. Diabetes mellitus . 6. Galactose consumption . 7. Shorter cycle length during addescence (which is also a predictor of higher basal FSH) .

17. Hormone Production after Menopause: • FSH → 10 – 20 fold increase > 40 lU/L . 2. L H → 3 fold increase . 3. Estradiol → ovary no longer screteor , mainly from peripheral conversion of estrone. 4. Progesterone → Very low level. 5. Androgen (androsterodione & testerone) Adrenal > ovaries. (women are more sensitive due to less opposition of estrogen → excessive facial hair growth and decrease breath size) . 6. Dehydroepiandrosterone (DHA) and its sulfate (DHAS) from adrenal.

18. Symptoms of menopause: (1 – 9) During the menopausal years, some women experiences sever multiple symptoms, physical and mental condition, where others show no reactions or minimal reactions that can go unnoticed. • Amenorrhea • Vasomotor instability → Hot flashes: ● Most common change occure during menopause are 75%. ● Self – limited usually resolve without treatment within 1 to 5 years. ● Sudden onset, common more at night a weak from sleep, last 2 – 4 minutes, usually occure several time per day. ● ↑ with stress and environment . • Sleep disturbance. • Genitourinary symptoms: 4 – i – Atropic vaginits → ● Vaginal dryness

19. Dyspareunia (stenosis, ↓ lubricant, ↓ sensation in the clitoral and valuar area) • Prurities (itching) 4 – ii Urinary symptoms: • Atrophic Urethritis. • Urethral Caruncle . • tress and urge urinary in continence . • Urithritis, systites (↑ UTI). 4 – iii Vaginal relaxation: • Cystocele . • Rectocele . • Uterine prolapse . 5. Psychophysiologic effects: • Depression . • Irritability . • Nervousness . • Frequent mood changes.

20. Breast pain . • Skin changes: ↓ collagen → wrinkling of the skin. • Joint pain . • Long – term issues: 9 a. Osteoporosis . 9 b. Cardio vascular disease . 9 c. Dementia (Alzheimer’s disease) .

21. Alzheimer’s Disease: • 3 times as many women as men. • Less frequency (60 % less) in estrogen users .

22. Cardio Vascular Disease: It is leading cause of death fallowed by caretrovascular disease, malignancy, motor accidents . There is good relation between age, lipid heredely, exercise, obesity.

23. Osteoporosis: • Bone is a very active organ . • It is a continuous process called bone remodeling ( resorption by osteoclast and formation by osteoblast). • Osteoporosis is most prevalent bone problem in the elderly, it is decreased bone mass with normal ratio of mineral to matrix, leading to an increase in fractures . • Subsequent risk of fracture from osteoporosis will depend on bone at time of menopause and rate of bone loss following menopause . → 0.7% loss by age of 30 years . → after menopause 1 – 1.5% of total bone mass loss per year. • Estrogen exerts a tonic suppression of remodeling and maintains a balance between osteoclastic & osteoblastic activity . • Post menopausal hormone therapy effectively reduces the osteoporatic fractures.

24. Osteoprosis effected by: • Age . • Calcium intact and absorption . • Exercises . • Smoking . • Estrogen . • Genetic .

25. Sign & Symptom of osteoprosis: • Back pain (major clinical symptom of vertebral compression fractures). • Decreased height and mobility and fractures of vertebral body, humerus, upper femur.

26. Diagnostic Tests: • Single – photon absorptiometry use a I- 125 density in the radius and the calcareous, are relatively in expensive, its dose correlate with vertebral bone density. • Dual – energy x ray absorptiometry (DEXA or DXA): → Provides good precision for all sites of osteoporotic fractures, and the radiation dose is much less than for a standard chart x-ray. • Quantitative computed tomography (CT) for bone density measurements can be performed or most commercial CT systems, however, radiation exposure is higher than DEXA .

27. DEXA D/D: primary , Secondary hyperparathyrodism, multiple myloma , leukemia, lymphoma, hyper thyrodism, metastatic cancer.

28. Treatment of Osteoprosis: Hormone treatment: I,II,III Post menopausal hormone therapy effectively reduces the number off all osteoporotic fractures. • Estrogen therapy: • It stabilizes the process of osteoporosis or prevents it’s from occurring. • Inhibits osteoclastic resorption activity. • Increase intestinal calcium absorption. • Increase 1, 25 – dihydraxy vitamin D (active form) .

29. Increases renal conservation of calcium . • Supports the survival of osteoblasts. • Estrogen > 5 year → ↓ Arm fraction 60% . • Estrogen + Ca + → ↓ 80% verfibal fraction . Dose: 0.3 mg/d. Conjugated estrogen 0.5 mg/d estradial + 15000 mg/d calcium. Protective effect of estrogen rapidly dispirates after treatment is stopped because estrogen with drowal is fallowed by rapid bone loss.

30. II Estrogen – progestational agents: Same result on bone density . III – Testosterone added to estrogen therapy program has been reported to provide no additional beneficial impact on bone or on relief from hot flushes. - Follow up assessment of hormones treated women not all women will maintain or gain bone density on it therapy 12% with no respond. NOTE: Estrogen do not consider as first line therapy for osteoporosis.

31. Selective Estrogen Agonists / Antagonists: • Raloxifene (Evista) & Tamoxifene: • Tamoxafine opposes the action of estrogen in breast tissue, but actually has an estrogenic like effect on the bone in post menopausal women. • First time for Rx osteoprosis. • Side effect is hot flashes . • Reloxifene (Evista) dose not cause uterine cancer as tamoxifen . • Exert no proliferatine effect on the endometrium but producess favorable resposes in bone and lipids. • Usually taken once daily.

32. II Bisphosphonates Alendronate (Fosamax) Risedronate (Actonel) • It enhance osteoclast a poptosis and inhibit bone resorption. The bisphosphonates bind to bone mineral where they remain for many years. • Use for both prevention and treatment of osteoporosis. • Should be taken or an empty stomach with full glass of water at least 30 min. before any other food or liquid intake in order to achieve adequate absorption. • Side effect esophageal injuries.

33. III Tibolone • Prevent bone loss in post menopausal women as effectively as estrogen therapy. • Dose ranging 0.3 – 25mg act through the estrogen receptor . IV Calcitonin: inhibet bone resorption, used in patient for whom hormone therapy is contraindicated, te increase bone density. dose 200 IV intranasel.

34. Calcium Supplement: • A positive calcium balance is mandatory to active adequate prevention against osteoporosis Dose: 1000 mg/d most efficient when single doses do not exceed 500 mg and when taken with a meal .

35. The beneficial impact of estrogen on bone is reduced in the absence of calcium supplementation. Vitamin D: • There is an age related decrease in the ability of the skin and the kidney to synthesize the active form of vitamin D and decreases in the ability of intestine to absorb dietary Vitamin – D. • It is now recommended that individuals over age 70 should add 800 units of vitamin D to calcium supplementation. • A large randomized trial in Finland documented a reduced rate of fractures in elderly women receiving supplementation of Vitamin D.

36. Life style modifications: • Physical activity (weight -bearing) as little as 30 min. a day for 3 days a weak, will increase the mineral content of bone in alden women. • Full combination of pharmacologic therapy, calcium and vitamin D and exercise, the beneficial impact lasts only as long as the therapy is continued. • Cigarette smoking and excessive alcohol consumption are associated with an increased risk of osteoporosis. ( ↑ 40 – 50% #) • A high coffee intake has been reported to be associated with an increased risk of osteoporosis.

37. Hormone Replacement therapy • Benefits of HRT: • Decrease colon cancer. • Decrease fractures (treatment of osteoporosis) . • Risks HRT: • Increase risk of stroke . • Increase risk of thrombo embolic fenomena . • Increase the risk of breast cancer and risk of recurrence. • Dose not protect cardiovascular events. Conclusion: Investigator concluded that the risks of HRT may out weigh its benefits in many women.