Postmenopausal period

Because the perimenopausal and postmenopausal periods are marked by many biologic and endocrinologic changes, women should inform their health care provider when they experience any signs and symptoms in order to discuss the most appropriate therapeutic approach. 

This is a proposal to help the clinician to counsel individual women. This process of individualization is crucial and is the best guarantee of a wise use of the different alternatives presently available for an efficient management of the postmenopausal period. Guidelines are only indications of the best choice for a majority of women, but, as health agents of our patients, we have the responsibility of determining how suitable they are for a given woman and introduce the appropriate corrections. In this context SERMs are an early alternative for osteoporosis prevention and treatment that provide an additive protective effect on the breast and are neutral on cardiovascular risk. 

Finally, sex steroids are also implicated in the pathophysiology of depression. Estrogen deficiency states, which occur in the postpartum and postmenopausal periods, are thought to play a role in the etiology of depression in some women. Likewise, severe testosterone deficiency in men is sometimes associated with depressive symptoms. Hormone replacement therapy in hypogonadal men and women may be associated with an improvement in mood and depressive symptoms. 

Androgens are sometimes given in combination with estrogens for replacement therapy in the postmenopausal period in an attempt to eliminate the endometrial bleeding that may occur when only estrogens are used and to enhance libido. They have been used for chemotherapy of breast tumors in premenopausal women. 

Estrogens can prevent accelerated bone loss during the immediate postmenopausal period and at least transiently increase bone in the postmenopausal woman. 

A 2-year randomized controlled study in 90 women compared the effects of oral tibolone doses of 1.25 mg/day and 2.5 mg/day on bone loss in the early postmenopausal period all took calcium 1000 mg/day. Vertebral and femoral bone density rose in both treated groups but fell in the control group, and bone turnover markers (urinary excretion of hydroxyproline/creatinine and plasma osteocalcin concentrations) were similarly affected favorably in the treated groups, as was the incidence of hot flushes/ flashes (5). Studies such as this still leave open the question of the advisability of continuing tibolone treatment over a longer period. While tibolone has indeed been shown to benefit mineral bone density, few data are available to show whether it lowers fracture incidence nor is it clear whether there is a link between tibolone and breast cancer (6). 

Estrogen replacement (see p. 264) is the most effective therapy for the prevention of postmenopausal bone loss. When initiated in the immediate postmenopausal period, estrogen prevents osteoporosis and reduces the risk of hip fracture. Raloxifene, a second-generation selective estrogen receptor modulator (see p. xxx), increases women s bone density without increasing the risk for endometrial cancer. In addition, raloxifene has recently been reported to decrease the risk of estrogen receptor-positive breast cancer. 

The incidence of ovarian cancer is higher in North America and Northern Europe than in Japan [3], The strongest patient related risk factor for ovarian cancer is increasing age. The vast majority of epithelial ovarian carcinomas are diagnosed in the postmenopausal period, with a mean age at diagnosis of 59 years. 

In addition to differences in rates of bone loss in the postmenopausal period, there are differences in the sites of loss and the type of bone affected. There is generally a rapid loss of trabecular bone, particularly during the first 5 yr, which predisposes to compression of the vertebrae, the commonest site of osteoporotic fracture. There is also a progressive, but slower, loss of cortical bone arising from resorption at the endosteal surface and resulting in thinning of the cortex. This is the cause of frequent fractures of the neck of the femur. Loss of one type of bone may ensue relatively independently of loss of the other. 

Postmenopausal bone loss is effectively inhibited by prophylactic administration of estrogen (Recker et al, 1977), but estrogen administration to osteoporotic patients (the conventional treatment) fails to restore lost bone. Estrogen appears to act primarily by putting a brake on bone resorption, i.e., it inhibits the action of parathyroid hormone, the primary stimulus to osteoclastic bone resorption. The mechanism of this inhibition is unknown receptors for estrogen have not been found in bone. A high intake of calcium during the postmenopausal period (up to 1500 mg/d) also is inhibitory (Heaney, 1981), presumably because it raises the level of ionized calcium in the serum sufficiently to suppress parathormone synthesis. 

Despite the limitations imposed by the physiology of the skin, several marketed controUed release transdermal dmg dehvery systems are available in the United States for example, scopolamine [51-34-3] for the treatment of motion sickness, nitroglycerin [55-63-0] for angina, estradiol [50-28-2] for the rehef of postmenopausal symptoms and osteoporosis, clonidine [4205-90-7] for the treatment of hypertension, fentanyl [437-38-7] as an analgesic, and nicotine [54-11-5] as an aid to smoking cessation. These systems are designed to dehver dmg for periods of one to seven days. 

An overall osteoprotective effect is associated with soy diets, the major active component being the isoflavones although the contribution (if any) of soy protein has to be clarified. The spine, rather than the femur, appears to be the most consistently protected bone site. The average daily intake in Japanese women is around 50 mg/day and appears to be sufficient to have a long-term protective effect on the spine. In non-Asian, postmenopausal women, the demonstrated effective dose is 80-90 mg/day. In future clinical studies, investigating the effect of isoflavones on bone metabolism, larger scale, randomized, controlled, intervention trials for longer time periods (1-3 years) will be necessary with a standardized source of soy protein/isoflavones and... 

Several studies have evaluated the long-term efficacy and safety of bisphosphonates in postmenopausal women. One study evaluated the use of alendronate over a 10-year period and found no difference in adverse effects between women who received alendronate for 10 years and women who discontinued alendronate after 5 years. Women who discontinued alendronate after 5 years continued to experience sustained increases in bone mineral density compared with baseline values and a reduction... 

Menopause is the permanent cessation of menses following the loss of ovarian follicular activity. Perimenopause is the period immediately prior to the menopause and the first year after menopause. Indications of postmenopausal hormone therapy include the short-term treatment of menopausal symptoms (i.e., hot flushes, night sweats, and urogenital atrophy). 

Healthy lifestyle is mandatory for all postmenopausal women together with adequate correction of detected risk factors. That is why this intervention is in the center of the diagram and concerns 100% of the women in this period. Then a decision must be made as to whether the woman s risk profile calls for any intervention beyond lifestyle improvement. The use of surrogate markers or risk scores can be useful in evaluating individual patients. 

Women with osteoporosis, either densitometric or established, and some cases of osteopenia with increased fracture risk require pharmacological intervention. Any intervention for osteoporosis is expected to be long lasting. Thus it is difficult to expect that interventions in young postmenopausal women could be maintained for the remainder of one s fife. The susceptibility to side effects changes either with the process of aging or the repeated use of a given product. Sequential treatment schedules, adapted to the risk profile of each period, would probably be more suitable. 

Experimental. A second study was conducted with nine postmenopausal women age 51-65 yr. The subjects were fed standardized meals for 19 weeks. The mean composition for the 7-day menus of natural foods as % of total calories was 15% protein, 50% carbohydrate, 35% fat with a P/S ratio of 0.7, 10 g/day crude fiber, and less than 300 mg/day cholesterol. In addition, the diets supplied 1289 mg calcium, 1832 mg phosphorus, 2561 mg sodium and 5099 mg potassium daily. The diets met the RDA for all other nutrients. Calorie levels were adjusted to maintain body weight. The experimental meals were fed during the last six weeks of this 19-week period. No more than one liquid meal was consumed by each subject in one week. Fasting and postprandial samples of blood and urine were collected as in the previous study. Diuresis was induced by scheduled consumption of water. 

Postmenopausal osteoporosis represents a period of accelerated loss of bone mass. The lower the preexisting bone mass, the earlier the clinical signs become manifest. 

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