MENOPAUSE

1. MENOPAUSE • PROF ROSHAN ARA QAZI • CHAIRPERSON • OBGYN LUMHS JAMSHORO

2. Definitions • Menopause: Is a permanent cessation of menstruation due to an intrinsic ovarian failure resulting in follicular inactivity. • Climacteric (Perimenopause): The few years that precede menopause. It represents the transition from reproductive to non-reproductive state.

3. Types of Menopause Natural Menopause: A retrospective diagnosis is established when menstruation stops for 12 months in the absence of an organic or a pathological cause. This usually occurs at the age of 45-50 years. If it occurs before the age of 40 years Premature Menopause.

4. Induced Menopause: • Surgical: after Bilateral Oophorectomy. • Radiological: after irradiation of the ovaries. • Chemotherapeutic: after exposure to chemotherapy during treatment of malignant diseases. The use of GnRh analogues > 6 months leads to menopausal symptoms, however these symptoms are reversible.

5. Pathophysiology Endocrine Changes: • Decrease in Inhibin production by the ovary. • Decrease in Oestradiol blood level. • Increase in Follicle Stimulating Hormone (FSH) production by the pituitary gland (> 30 lU/ml) • Increase in Lutenizing Hormone (LH) production.

6. Oestrogens decreases markedly and is unopposed i.e. no Progesterone. • Estrone (E1) is the main oestrogen after menopause due to peripheral conversion of Androstenedione to Estrone in the fat  Thus obese women are liable to endometrial hyperplasia & cancer.

7. The menstruation may stop abruptly but more commonly after a period of Oligo- or Hypo-meorrhoea. • During this climacteric period, bleeding from a proliferative endometrium (because of anovulation) may be irregular and acyclic. In such cases, endometrial carcinoma should be excluded before attributing it to the natural physiological hormonal changes.

8. Morphological Changes Characterized by Atrophy (Oestrogen Lack): • The ovaries look small and fibrous. • The uterus becomes smaller and the cervix flushes with the vaginal vault. • The vagina looks pale with loss of rugae and acidity. The vaginal smear becomes atrophic. • The labia majora becomes smaller and the vulval orifice gaps. • Ligaments become weak with tendency to prolapse • The breasts become smaller and flabby.

9. Symptoms • Collectively known as the Menopausal Syndrome and are related to Oestrogen deficiency. • About 50% of women do not develop these symptoms. • Duration and severity vary among different women. • May occur before, during, or after cessation of the menstruation.

10. Vasomotor Symptoms (Hot Flushes): A wave of heat over the chest, neck, and face followed by cold sweating is the most characteristic symptom occurring for few seconds or minutes. Frequency varies and may occur at night disturbing the sleep. Palpitation, headache, and dizziness may also occur. The attacks are due to vasodilatation followed by vasoconstriction. Gastrointestinal Symptoms: constipation, and abdominal distension.

11. Urinary Symptoms: frequency, dysuria, stress incontinence with predisposition for recurrent urinary tract infections. Vaginal Symptoms: atrophy and dryness leads to dyspareunia. Decrease in vaginal acidity predisposes to senile vaginitis. ± Hirsutism, Uterine Prolapse. Nervous and Psychological Symptoms: Anxiety, irritability, mood changes, lack of concentration, and insomnia.

12. Special Investigations • If any doubt exists about the diagnosis of Menopause  measurement of serum FSH level is done. Elevation of FSH level to 20 mIU/ml indicates early ovarian failure. If FSH ≥ 40 mIU/ml or LH ≥ 25 mIU/ml  Menopause. • Few years later, levels of FSH & LH drop due to pituitary exhaustion.

13. Remote Health HazardsOsteoporosis Osteoporosis or decreased bone mass density (BMD) is due to Oestrogen lack with increased risk of fractures from a minor fall. It affects: vertebrae, femoral neck, distal radius, and calcaneus. Risk factors: are smoking, caffeine consumption, sedentary life, genetic (white race), familial, and low body weight. 50% of women over the age of 50 years will experience an osteoporosis-related fracture in their lifetime.

14. Osteoporosis Asian women experience fewer menopausal symptoms than Western women as their traditional diet contains high level of Phytoestrogens(200 mg daily compared with < 5 mg daily in western diet( derived from natural plants (Soya beans, Cereals, Fruit & Vegetables). Most patients are asymptomatic until the disease is advanced and multiple vertebral fractures have occurred. Therefore, there is a need for early screening, diagnosis, and intervention to prevent fractures.

15. Osteoporosis Clinical features of a patient with multiple vertebral fractures include a progressive loss in height, increased kyphosis, loss of shoulder elevation, forward flexion of the neck, approximation of the rib cage to the pelvis, and a change in the center of gravity.

16. Osteoporosis While there is a slow decline in bone mass for both sexes with age, women experience a rapid acceleration of bone loss following menopause. Bone density drops about 1% annually after menopause for most women, but about half that (0.5% annually) for men after age 50. The more rapid loss of bone strength leaves women at increased risk for fracture approximately 10 years earlier than men.

17. Osteoporosis • Dual-energy X-ray absorptiometry (DXA) of the spine and hip are the gold standard of BMD measurement. • DXA is a low dose X-ray of two different energies used to distinguish between bone and soft tissue  giving a very accurate measurement of bone density.

18. Osteoporosis Non-pharmacologic treatment: • Change lifestyle. • Diet Modification. • Weight-bearing Exercises. • Smoking Cessation. • Avoid Alcohol intake. • Physical Therapy. • Providing assistive devices if necessary.

19. Pharmacologic treatment: • Calcium supplementation 1200 mg/day. • HRT: can be used for no more than 5 years. • Bisphosphonates: e.g. alendronate 5-10 mg, risedronate (5mg). It inhibits bone resorption. • Raloxifene (SERM): 60 mg/day it has a combined oestrogen-like effect (on bone) and anti-oestrogenic effect (on breast and uterus). It can be used for osteoporosis if HRT is contraindicated or refused. • Calcitonin: a nasal spray 200 mg/day inhibits bone resorption by decreasing osteoclasts activity. • Phytoestrogens: plant substances found in food similar in it’s action to oestrogen e.g. Soya beans.

20. Remote Health Hazards Cardiovascular Diseases Cardiovascular diseases Because of losing the protective effect of Oestrogen  hypercholesterolaemia, increase in Low Density Lipoproteins (LDL) and decrease in High Density Lipoproteins (HDL)  myocardial infarction, atherosclerosis, hypertension, and stroke.

21. Management of Menopause • Examination: General, Breast, and Pelvic to exclude a disease that may contraindicate the use of Hormone Replacement Therapy. • Assurance about the physiological nature of the symptoms may be the only treatment needed. • Regulation of diet and exercises. • Sedatives, Tranquilizers, or Antidepressants if needed. • Hormone Replacement Therapy (HRT).

22. Premature Menopause Menopause occurs at age earlier < 40 years. Etiology: • Constitutional. • Hypergonadotrophic hypogonadism: Ovarian failure e.g. Turner syndrome or Ovarian destruction by radiotherapy / chemotherapy, or Surgical removal. Diagnosis: Serum FSH > 40 mlU/ml.

23. Delayed Menopause Menopause is delayed beyond age of > 55 years. Etiology: a. Constitutional. b. Oestrogen producing ovarian tumors or uterine fibroids. Management: as a case of postmenopausal bleeding, due to liability to develop endometrial cancer.

24. HORMONE REPLACEMENT THERAPY (HRT)

25. Oestrogens Aim: • To control hot flushes. • To prevent osteoporosis & angina. The natural compounds are preferred: • Estradiol valerate 1-2 mgm/day. • Conjugated Oestrogen (Premarin) 0.625 mgm/day.

26. The Oral route is easy, cheap, and convenient. However, it’s hepatic first pass reduces the biological activity (converted to Estrone) and can activates certain liver enzymes. • The Transdermal route (by skin patches) or administration by subcutaneous implants, and vaginal cream avoid the above mentioned side effects. • Must be combined with a Progestin when given to women with an intact uterus to avoid endometrial hyperplasia or carcinoma. However Oestrogen alone is prescribed for hysterectomized patients.

27. Progestagens Aim:  To prevent endometrial hyperplasia / endometrial cancer when given at least 14 days/cycle. Mechanism: • It decreases the endometrial estrogen receptors. • It has a direct anti-mitotic effect on the endometrial glands.

28. Synthetic compounds with progestational activity: • Testosterone derivatives: • Norgestrel 0.05 mgm/day. • Norethisterone acetate 1 mgm/day. • Gestodine 50 mcg/day. • Progesterone derivatives: • Micronized progesterone 200 mgm/day. • Medroxyprogesterone acetate 2.5 mgm/day.

29. Indications of HRT Although all menopausal women suffer from Oestrogen lack, not all of them need HRT. World­wide, only about 20% of menopausal women use HRT for 1-2 years: • Symptomatic menopausal women to relieve menopausal symptoms. • Premature or induced menopause. • To prevent osteoporosis for a minority of women with one or more risk factors. Beneficial effects occur only during treatment and stop with cessation of treatment.

30. Contraindications of HRT • Absolute: Breast and endometrial cancer, active liver diseases, uncontrolled hypertension, and thrombo-embolic diseases. • Relative: Uterine fibroid, endometriosis, and migraine

31. Regimen of HRT Sequential Regimen: Oestrogen alone for 2 weeks followed by a combination of Oestrogen and Progestagen for another 2 weeks  Withdrawal bleeding occurs in 80% of cases. Combined Regimen: Daily continuous combination of Oestrogen + Progestagen allows using a lower dose of progestagen resulting in less bloating, weight gain, and mastalgia  Withdrawal bleeding occurs in 20% of cases. Oestrogen alone: Used only in absence of uterus (Hysterectomized women).

32. Regimen of HRT

33. Benefits of HRT • Relieves menopausal symptoms. • Prevents urogenital atrophy and osteoporosis. • Decreases risk of colonic cancer and Alzheimer disease.

34. Long-term Risks of HRT • Slight increased risk for Breast Cancer if used for more than 5 years. • Slight increased risk of Thromboembolic disease during the 1ST y of use. • Increased risk of Endometrial Cancer with Oestrogen-only regimen.  For those reasons, use of HRT should not exceed 5 years.

35. Follow-up of HRT clients • Periodic Mammography / 1-2 years. • Pap smear yearly. • Bone densitometry. • Pelvic Ultrasonography. • Endometrial biopsy for abnormal bleeding pattern to avoid delay in the diagnosis of endometrial carcinoma.

36. Counseling • The decision to use HRT should be made jointly by the patient and her doctor with full consideration of all known and possible benefits and risks. • Use HRT for the Shortest possible duration in the Smallest effective dose.

37. Thank You