Bisphosphonates

Bisphosphonates are chemical analogs of pyrophosphate which bind strongly to bone to exert anti-resorptive effects which lead to improved bone density. They become incorporated at the site of bone resorption (pits) where they: (1) change physico-chemical characteristics of the bone and reduce the rate of its dissolution; (2) reduce the rate of formation of new pits; and (3) exert cytotoxic effects on osteoclasts. Bisphosphonates are poorly absorbed orally and have to be taken on an empty stomach. Three types of bisphosphonates are widely used — etidronate, alendronate and risedronate. All three increase the bone mineral density at clinically relevant site (radius, spine, neck of femur) and decrease the incidence of fractures. When taken for two years positive changes in bone density of 3-8% have been reported. Alendronate is available as a once a week dose (70 mg) which makes administration even simpler. For many women with osteoporosis, bisphosphonates may be the treatment of first choice.

Phytoestrogens

Phytoestrogens have a structure resembling estrogen and are found in plants. They have mixed estrogenic/antiestrogenic properties, the estrogenic effect being 500-1000 times less than that of estradiol. There are several different classes of phytoestrogen, but most prominent in the human diet are phenolic ones — flavones, isoflavones, lignans, coumestans. Isoflavones are the most common form of phytoestrogens and are found in a variety of fruits and vegetables but are particularly abundant in leguminous plants and especially soy. The phytoestrogens found in foods are ‘precursors’ because they undergo complex transformation in the gut, being metabolized by the bacteria, and then in the body. The end result is appearance in the blood of the active constituents: daidzein, genistein and equol. The daily consumption of isoflavones in Japan and other Asian communities has been estimated at 25-45 mg/day, but it is much less in the typical ‘Western’ diet. Observational studies and laboratory experiments have linked high consumption of phytoestrogens with low incidence of CVD, osteoporosis and cancer of the breast, colon, prostate and uterus. Those observational data have various epidemiologic deficiencies and cannot prove a cause and effect relationship.

The only rigorously tested association is between intake of phytoestrogen and hot flashes. Randomized controlled trials have shown that phytoestrogens (in the form of soy flour) have modest activity in curtailing the severity of hot flashes. It seems, therefore, sensible that menopausal women should be encouraged to increase their intake of phytoestrogens, which not only may relieve their hot flashes, but may also have wider health benefits. Daily intake of 20-60 g of soy protein or soy flour has been most widely used in clinical studies, but this may not be easily achievable in day-to-day life. Phytoestrogen tablets and isolates are less effective. According to two studies ipriflavone (synthetic isoflavone) prevents bone loss in postmenopausal women with low bone mass. Other studies investigating the effects of phytoestrogens on lipid metabolism and the cardiovascular system demonstrated a decrease in cholesterol and improved vascular function. No good data is available on phytoestrogens and cancer.

Herbs

Medicinal herbs are crude drugs of plant origin used for treatment of diseases, often of a chronic nature, or to promote good health. Herbs for treatment of menopausal symptoms have been available long before the discovery of hormone replacement therapy. A number of such herbs are currently widely advertised by the health food industry, which claims improvements in hot flashes, mood and general well-being. Some examples are ginkgo (Ginkgo biloba), gingseng (Panax gingseng), St John’s wort (Hypericum perforatum) and valerian (Valeriana officinalis). Of these, only St John’s wort has been properly researched and has been shown to be effective in mild to moderate depression. Its side-effects include gastrointestinal symptoms, allergic reactions, dizziness, confusion, tiredness/ sedation and a dry mouth. St John’s wort interacts with many medications in a way which may reduce or potentiate their efficacy and/or plasma concentration, because it reduces the cytochrome P450 enzyme system. Medications the activity of which is diminished by St John’s wort are warfarin, cyclosporin, oral contraceptives, anticonvulsants and digoxin. The effect of triptans (i.e., sumatriptan) and selective serotonin reuptake inhibitors (i.e., fluoxetine) is increased, which leads to increased incidence of adverse reactions. Doctors should always ask about self-medication, including the use of herbal products. Natural progesterone creams are not efficacious in prevention or treatment of osteoporosis. Their role in abating hot flashes is still under investigation. Indeed, the Medicines Control Agency issued advice that women using oral contraceptives should not use St John’s wort because the latter might result in unwanted pregnancy.

Diet, exercise, smoking and weight control

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