Menopause PDF

Menopause The menopause is defined as the woman’s final menstrual period and the accepted confirmation of this is made retrospectively after 1 year of amenorrhoea. The cause of the menopause is cessation of regular ovarian function. The average age of the menopause remaining at a median age of betw...

Menopause The menopause is defined as the woman’s final menstrual period and the accepted confirmation of this is made retrospectively after 1 year of amenorrhoea. The cause of the menopause is cessation of regular ovarian function. The average age of the menopause remaining at a median age of between 51 and 52 years, with 95% of women attaining menopause between the age of 45 and 55 years. An elevated serum FSH in association with a low serum oestradiol may be suggestive of the menopause, but as this combination of levels can occur during a normal menstrual cycle, this test can be misleading. Two raised FSH levels (>30 IU) at least 6 weeks apart are required to make a diagnosis. Hormonal changes in menopause Non physiological menopause Premature ovarian insufficiency If menopause occurs before the age of 40 years It is thought to occur in approximately 1% of women under 40 years and 0.1% under 30 years. For young women who wish to conceive, gamete donation is the only option. POI is usually diagnosed following either primary or secondary amenorrhoea. Women who have a diagnosis of POI can experience unpredictable spontaneous ovarian activity, resulting in irregular vaginal bleeding and the small risk of pregnancy. Principal causes are Primary Chromosome anomalies (e.g. Turner’s, fragile X) Autoimmune disease (e.g. hypothyroidism, Addison’s, myasthenia gravis) Enzyme deficiencies (e.g. galactosaemia, 17a-hydroxylase deficiency) Secondary Chemotherapy or radiotherapy Infections (e.g. tuberculosis, mumps, malaria, varicella) Iatrogenic menopause – medical treatments and menopause after cancer treatment If GnRH is given in a constant high dose, it desensitizes the GnRH receptor and reduces LH and FSH release. Drugs that are GnRH agonists (e.g. buserelin and goserelin) can be used as treatments for endometriosis and other gynaecological problems. This will induce a temporary menopause with a relatively rapid onset, which can be managed with the introduction of hormone therapies and other drugs to relieve some of the unwanted menopausal symptoms – known as add-back therapy. Iatrogenic menopause – surgical menopause Women may be placed into surgical menopause aiming to permanently treat benign gynaecological conditions such as menstrual disorders, fibroids and endometriosis. Bilateral salpingo-oophorectomy (BSO) may also be performed prophylactically for women at high risk of inherited malignancies such as breast and ovarian cancer, with BRCA 1 and 2 gene mutation screening. How women are affected by the menopause Effects of the menopause by time of onset Immediate (0–5 years) Vasomotor symptoms, (e.g. hot flushes, night sweats) Psychological symptoms (e.g. labile mood, anxiety, tearfulness) Loss of concentration, poor memory Joint aches and pains Dry and itchy skin Hair changes Decreased sexual desire Intermediate (3–10 years) Vaginal dryness, soreness Dyspareunia Urgency of urine Recurrent urinary tract infections Urogenital prolapse Long term (>10 years) Osteoporosis Cardiovascular disease Dementia Central nervous system Vasomotor symptoms The colloquial term applied to vasomotor symptoms is ‘hot flush’, and when a hot flush occurs at night it is termed ‘night sweat’. The exact aetiology of a vasomotor symptom is unknown but is thought to be loss of the modulating effect of oestrogen on serotinergic receptors within the thermoregulatory centre in the brain, resulting in exaggerated peripheral vasodilatory responses to minor atmospheric changes in temperature. Hot flushes occur in up to 80% of women, with less than 30% seeking help. Perhaps the most distressing effect of vasomotor symptoms is through the occurrence of night sweats. The woman may be asleep at the time of the sweat, but during the episode she can be fully woken or her level of sleep can be converted from deep rapid eye movement (REM) sleep to a shallower sleep that is less refreshing. Such disturbances lead to tiredness, exhaustion, poor performance during the day and impaired quality of life. While hot flushes tend to appear unpredictably, additional triggers include alcohol, caffeine and smoking. Women with a high body mass index (BMI) tend to get worse vasomotor symptoms. Psychological symptoms menopause is associated with low mood, irritability, lack of energy, tiredness and impaired quality of life from the early perimenopausal period.  Endometrial effects The initial irregular or scanty vaginal bleeding is due to the reduction in oestrogenic endometrial stimulation with failing ovarian function, ultimately resulting in periods completely stopping when the endometrium is no longer stimulated. Episodic and infrequent ovulation with fluctuations in oestrogen levels leads to unpredictable progestogenic levels, which usually has the effect of inadequate regular endometrial shedding. This can then lead to some women experiencing irregular heavy bleeding. The urogenital tract and vulvovaginal atrophy Once oestrogen levels start to fall in the perimenopausal years, many women, particularly those who are sexually active, may become aware of vaginal dryness, irritation, burning, soreness and dyspareunia. incontinence and prolapse,. The incidence of urinary tract infections is also increased, Examination of women with postmenopausal urogenital atrophy normally demonstrates dryness affecting most of the surfaces of the vagina along with pallor and, in extreme cases, small petechial haemorrhages. Older women may also have shrinkage and fusion of the labia along with narrowing of the vaginal introitus. Bone health the skeleton is maintained by a constant process of remodelling, with bone being laid down by osteoblasts and resorbed by osteoclasts. The balance of the rates of resorption vs. deposition is affected by many different factors, one of which is oestrogen. Bone density naturally increases during childhood, reaching a peak between 20 and 30 years of age. Males generally achieve a greater peak bone density in comparison to females. After peak bone mass attainment in women there is a steady decline until the menopause, then an accelerated phase of bone loss until 60 years, followed by further steady decline until death. After the age of 60 in women, the likelihood of osteoporotic fractures of the hip and spine increases. Osteoporosis is defined as ‘a skeletal disorder characterized by compromised bone strength predisposing to an increased risk of fracture’. It is more frequent in women than men with an approximate ratio of 4:1 Risk factors for osteoporosis Family history of osteoporosis or hip fracture. Smoking. Alcoholism. Long-term steroid use. POI and hypogonadism. Medical treatment of gynaecological conditions with induced menopause. Disorders of thyroid and parathyroid metabolism. Immobility. Disorders of gut absorption, malnutrition, liver disease. Cardiovascular system Approximately 30% of all deaths occur as a result of ischaemic heart disease and stroke. During the menopausal transition there are several changes in the female physiology that can influence individual risk of CVD. These include lifestyle issues such as nutrition and exercise, changes in the distribution in fat from a more gynaecoid (fat on breasts and hips) to android (abdominal fat deposition) and changes in serum lipid levels that include increases in triglycerides, total cholesterol and low-density lipoprotein (LDL) cholesterol with reduction in high-density lipoprotein (HDL) cholesterol. Oestrogen also has a supportive effect on the vessel wall that favours vasodilatation and prevents atherogenesis; effects that are reduced after the menopause. Management Diet and lifestyle regular exercise, stopping smoking and reducing alcohol consumption. Normal BMI Reduction of calorie intake Fewer, less severe vasomotor symptoms Beneficial effects on bone loss Reduction in incidence of breast cancer Reduction in incidence of endometrial cancer Reduction of CVD Stopping smoking Prevention of lung cancer Reduction of CVD Beneficial effects on bone loss Non-hormonal approaches  Hormonal replacement therapy Types of hormones contained in HRT Oestrogens If oestrogen is given without progestogenic opposition, there is a risk that in time endometrial hyperplasia and cancer may develop. Systemic oestrogen-only HRT is suitable for women who no longer have a uterus following a hysterectomy. Oestrogen with progestogen The administration of progestogen is necessary to protect the endometrium in women who have not had a hysterectomy. It is normally given cyclically in preparations over a 28-day cycle, of which 16–18 days will provide oestrogen alone and 10–12 days will provide oestrogen and progesterone combined (cyclical HRT). This results in regular monthly menstruation and is suitable for women during the perimenopause or early postmenopausal years. Oestrogen and progesterone may be given continuously (continuous combined HRT) to women who are known to be postmenopausal or over the age of 54 years. These are usually preparations with the same dose of daily oestrogen combined with a smaller dose of progestogen taken every day. These regimes normally result in about 90% of women not experiencing vaginal bleeding. Testosterone has traditionally been given to women with disorders of sexual desire and energy levels who have failed to respond to normal HRT. The two main routes of HRT delivery are oral and transdermal. The oral route is convenient and cheap but does influence lipid metabolism and the coagulation system through its effects on the liver during first-pass metabolism. The transdermal route, either given as patches applied to the skin on the trunk or as measured amounts of gel, is also effective, with the advantage of delivery of oestradiol directly into the circulation, avoiding the above potentially adverse effects on the liver and the coagulation system. Oestradiol is also available as small vaginal tablets and a vaginal ring, and oestriol as measured dose vaginal creams that are important in the management of lower genital tract symptoms. Progestogen in the form of levonorgestrel may be administered as an intrauterine releasing system (IUS), Mirena®. This device not only provides contraception and control of troublesome bleeding, but also provides endometrial protection for up to 5 years Tibilone a synthetic hormone preparation. Options for osteoporosis prevention and treatment: 1-Nonhormonal treatment: a- Lifestyle modification includes:.Supplementary calcium –daily intake of 1-1.5 g. can reduce osteoporosis.. Exercise-weight bearing exercises, walking, jogging..Vitamin D –supplementation of vitamin D3 (1500-2000 IU/day) along with calcium can reduce osteoporosis and fractures. Exposure to sunlight enhances synthesis of cholecalciferol vitamin D3 in the skin..Cessation of smoking and alcohol , high coffee intake ,reducing medications that causes bone loss(corticosteroids).Nutritious diet – balanced with calcium and protein is helpful..Evaluation of bone density(hip) should be done periodically. b-Phytoestrogen containing isoflavones are found to lower the incidence of vasomotor, osteoporosis and cardiovascular disease.it reduce the risk of breast and endometrial cancer. c-Biphosphonates: are pyrophosphate analogues which interfere with osteoclastic resorption e.g. Alendronate used to prevent and treat osteoporosis and hip and spine fractures. 2-Hormonal treatment: -ostradiol 2mg or equivalent needed to increase rather than maintain bone mass. -combined oestrogen –progestogen. -tibilone. Key benefits of HRT vasomotor symptoms; sleep patterns; performance during the day. Prevention of osteoporosis: increased bone mineral density; reduced incidence of fragility fractures. benefit of HRT on the incidence and mortality of colon cancer, Lower genital tract: dryness; soreness; dyspareunia , cystitis and occasionally dysuria; CVD: preventative effect if started early in menopause. Contraindications and potential side-effects Absolute contraindications: suspected pregnancy; breast cancer; endometrial cancer; active liver disease; uncontrolled hypertension; known current venous thromboembolism (VTE); known thrombophilia (e.g. Factor V leiden); otosclerosis. Relative contraindications: uninvestigated abnormal bleeding; large uterine fibroids; past history of benign breast disease; unconfirmed personal history or a strong family history of VTE; chronic stable liver disease; migraine with aura. Side-effects associated with oestrogen: breast tenderness or swelling; nausea; leg cramps; headaches. Side-effects associated with progestogen: fluid retention; breast tenderness; headaches; mood swings; depression; acne. Risks of hormone therapy Breast cancer Useful figures to quote are that the background risk of breast cancer in the 50–59 year age group is 22.5 per 1,000 women for 7.5 years use of HRT and there may be an additional 2–6 cancers with combined HRT use, which reduces after stopping HRT. Cardiovascular disease and stroke As discussed above, most of the effects of HRT on the cardiovascular system when given to younger women are beneficial. However, when given to older women the effects may become deleterious. Stroke incidence has a similar age effect, with the increased incidence greater in the older woman, thought to be an increase of an additional 2 women per 10,000 women per year when on HRT. Venous thromboembolism The influence of HRT on the clotting system is similar to that of the oral contraceptive. The background incidence of all VTE in women over 50 is low (approximately 15–20 per 10,000) and HRT doubles this risk. There is evidence to suggest that transdermal HRT, through its avoidance of effects on the liver, may not have such a great effect on VTE incidence.