MENOPAUSE

1. MENOPAUSE DR.FATIN

2. Definitions: Greek words menos = month Pausos = ending MENOPAUSE: Is the permanent cessation of menstruation resulting from the loss of ovarian follicular activity. Natural menopause is secondary amenorrhoea for more than 6 months ( some say 12 months ) in a woman aged 45 years or over without another pathological cause. The average age at which menopause occurs is 51 years. Menopause before the age of 40 years is called premature ovarian failure.

3. THE CLIMECTERIC: In Greek Klimakter = rung of a ladder. It is the period of time usually between 45 and 55 years of age , during which the transition from the reproductive to the non-reproductive state occurs. It is attended by a variety of signs and symptoms and metabolic adjustments due to a major reduction in circulating oestrogen level.

4. Physiological Changes Hypothalamus-Pituitary-Ovarian Axis Changes: During the reproductive life of a woman, gonadotropin-releasing hormone (GnRH) is released in a pulsatile fashion by the arcuate nucleus of the medio- basal hypothalamus. It binds to GnRH receptors on the pituitary gonadotrophs to stimulate cyclic luteinizing hormone (LH) and FSH release. These gonadotropins, in turn, stimulate the production of the ovarian steroids: estrogen, progesterone, and also inhibin.

5. During the reproductive years, estrogen and progesterone exert positive and negative feedback on pituitary gonadotropin production and on the amplitude and frequency of GnRH release. Produced in the granulosa cells, inhibin exerts important negative feedback influence over FSH secretion from the pituitary. This tightly regulated endocrine system leads to ovulatory menstrual cycles that are regular and predictable.

6. The transition from ovulatory cycles to menopause typically begins in the late 40s and in early menopausal transition . Levels of FSH rise slightly and lead to an increased ovarian follicular response with overall higher estrogen levels . There is an increase in serum estrogen levels, produced from an increased number of follicles in the stimulated cohort responding to rising FSH levels.

7. Also, during this time ovarian follicles undergo an accelerated rate of loss until eventually, in the late menopausal transition, the supply of follicles is depleted. These changes, including the increase in FSH levels, reflect the reduced quality and capability of aging follicles to secrete inhibin .

8. As follicular depletion continues, episodes of anovulation become more common . With ovarian failure in the menopause , ovarian steroid hormone release ceases,. Subsequently, GnRH is released at maximal frequency and amplitude. As a result, circulating FSH and LH levels rise up to fourfold higher than in the reproductive years.

9. Causes of menopause: PREMATURE OVARIAN FAILURE ( POF ): Is menopause before the age of 40 years ( some say 45 years ). Such patients exhibit: - Low plasma oestradiol ( E2 ) usually less than 150 pmol/ L - high levels of FSH and LH and - signs and symptoms of suggestive of oestrogen deficiency. POF may be associated with other autoimmune endocrinopathies and in about half of patients other auto antibodies are present, however the precise site of action of an antibody attack on the hypothalamo-pituitary-ovarian axis is unknown. POF may be induced during management of malignant disease in young women through chemotherapy, pelvic radiotherapy, or creating artificial menopause to suppress oestrogen secretion from the ovary in premenopausal women treated with radiation for breast cancer.

10. Principle causes of premature ovarian failure: Primary causes: -Chromosomal anomalies e.g turner syndrome and fragile x. -auto-immune disease e.g hypothyroidism,Addison, myasthenia gravis. - enzyme deficiency e.g galatosaemia, 17α hydroxylase def. Secondary causes: -surgical menopause after bilateral oopherectomy. - chemotherapy or radiation. - infection e.g TB ,mump, malaria,varicella.

11. RESISTANT OVARY SYNDROME: Here a group of patients with premature ovarian failure have the same clinical picture but the biological appearances of the ovary are normal with abundant primordial follicles unlike those with POF in which the ovaries look like those of menopausal women.

12. SURGICAL MENOPAUSE: Causes: -Following bilateral oophorectomy for any reason, this will cause immediate menopause. -Following hysterectomy in premenopausal patients even if both ovaries are conserved, POF may supervene. The median age of menopause here is 47 – 48 years instead of the expected age of 51 years. Because of amenorrhoea due to hysterectomy , menopause here is diagnosed by symptomatology and endocrine tests.

13. SYMPTOMS OF MENOPAUSE: These may begin before the actual cessation of menstruation with the relative fall of oestrogen level and before the level of menopause is reached ( less than 100 pmol/L ). 1-PHYSICAL SYMPTOMS: A-The classical vasomotor symptoms of hot flushes and night sweats: - Occur in at least 70% of perimenopausal women. Their frequency varies from a few to several dozens per day and the duration may be from a few weeks to many years.

15. Hot flushes are a vascular response to a central disturbance of the thermoregulatory centre in the hypothalamus. There is a downshift of the set-point of this centre such that there is a frequent central misapprehension that body temperature is too high, this in turn leads to activation of the physiological mechanisms such as cutaneous flushing and perspiration which result in heat loss by radiation and by the loss of the latent heat by vaporization.

16. - At night these attacks may lead to frequent awakening of the patient and result in certain psychological symptoms such as irritability and short term memory impairment. B- Tiredness C- Insomnia D- Vaginal dryness which leads to dyspareunia and affects the womens' relationship with their partners. With oestrogen deficiency vaginal epithelium becomes thin and poorly moisturised.

18. E- Urinary symptoms: menopausal women often complain of dysuria, frequency, and urgency which suggest a urinary tract infection ( UTI ) but associated with a negative urine culture. Stress incontinence may also be present. F- Skeletal system: About 20% of body bone is highly sensitive to oestrogen ( trabecular bone ) as found in the vertebrae, distal radius, femoral neck and the calcaneus.

19. Oestrogen keeps the balance between bone formation and bone resorption and after menopause there will be greater bone resorption than formation. As trabecular bone is a shock-absorbing bone so it becomes more liable to fracture after minimal or moderate trauma. The net result is that after menopause there is a progressive rise in the incidence of fracture of the trabecular sites. Traumatic fracture affects the distal radius and femoral neck, whereas non-traumatic fracture affects the vertebrae.

20. Factors that increase the risk of osteoporosis and fracture with minimal trauma: - Non-modifieable :age, race, family history, history of fracture, early menopause. - Modifiable: decrease ca. and vitamin D intake, smoking, sedentary life style, low body weight, alcohol intake. -Anovulation during reproductive years(eg, secondary excess exercise or eating disorder) -Early ovarian failure or bilateral oopherectomy.

21. Medical conditions associated with an increased risk of osteoporosis like, thyrotoxicosis, Hyperparathyroidism, Chronic renal disease, .Diseases requiring systemic corticosteroid use. -More than 6 months Secondary amenorrhea(excepting pregnancy).

22. Osteoporosis

23. G- Cardiovascular system: Oestrogen has a protective effect against cardiovascular disease in premenopausal women so myocardial infarction is much lower than in men of matched ages. Oestrogen deficiency causes the following atherogenic changes in lipid profile : total cholestrol : ↑ high-density lipoprotein ( HDL ) : ↓ low-density lipoprotein ( LDL ) : ↑ Triglycerides : ↔

24. Oesradiol also is known to stimulate the enzyme nitrogen synthase, whose product, nitric oxide is both a vasodilator and an oxidant for lipoprotein accumulating in the subintima of the vessel wall. Loss of oestrogen can thus result in a promotion of both atherogenesis and vasoconstriction.

25. 2-PSYCHLOGICAL SYMPTOMS: Mood swings Anxiety Loss of short-term memory Lack of concentration Loss of self-confidence Depression

26. Diagnosis of menopause: 1.cessation of menstruation for consecutive 12 months during climacteric. 2.Appearance of menopausal symptoms hot flush and night sweats. 3.vaginal cylology showing maturation index of at least 10/85/5(features of low estrogen). 4.serum estradiol:less than 20 pg/ml. 5.serum FSH and LH: more than 40 mlU/ml(three values at weekly interval

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