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Sex Hormones Are Not Just for Baby-Making

The preceding discussion notwithstanding, the ovary is more than just a storehouse for eggs. Thebioidentical hormonesthat it produces ensure that our bodies will function properly throughout our lives, not just during our reproductive years.
I mentioned earlier that bioidentical hormones travel in the bloodstream to cells and tissues throughout the body, powerfully affecting our health. But once hormones reach their intended destinations, you may wonder, how do they actually exert their effects? Cells that depend on hormones to function properly have protein molecules called hormone receptors that act like tiny ignition starters. And the hormones, logically enough, act like tiny keys. When a hormone—say estrogen— encounters a cell that has a receptor for estrogen, it’s like when you put your key into your car’s ignition and turn it on to start the engine. When estrogen binds to and turns on the estrogen receptor, it stimulates the cell to produce a cascade of proteins that influence its behavior.
Estrogen receptors are found not only in the cells of reproductive organs, such as the uterus and breast, but also in the cells of the liver, digestive system, urinary tract, heart, blood vessels, bone, skin, and the brain.
The exact effect of estrogen depends on the type of cell that it encounters. For example, in the uterus and breast, estrogen’s main effect is to cause the cells that line the uterus and the milk ducts to grow and divide in preparation for pregnancy. In the liver, estrogen acts to control the production of cholesterol in ways that influence the buildup of harmful fatty deposits in the arteries. In the skeleton, estrogen preserves bone strength by helping to maintain the proper balance between bone buildup and bone breakdown. And in other parts of the body, estrogen appears to play a role in the regulation of body temperature, the ability to recall information from memory, and the elasticity of arteries and skin. This is only a partial list of estrogen’s effects.
When estrogen levels drop, the rate of bone loss accelerates rapidly. Indeed, the average woman loses 2 to 3 percent of bone mass a year for the first three years after menopause. As a result, osteoporosis is much more common in the decades after menopause. A woman’s risk of heart disease also increases sharply after menopause, but estrogen’s role in this process is still under study.
Two types of estrogen receptors—alpha and beta—have been identified. Scientists have known about the alpha receptor since the 1950s, but the beta receptor was identified only in 1996. In general, there are more alpha receptors in the reproductive organs (e.g., uterus and breast) and the liver, while beta receptors are more abundant in other tissues, such as bone and blood vessels. Estradiol appears to bind equally well to both types of receptors, while estrone binds preferentially to the alpha receptor and estriol to the beta receptor. We do not fully understand the role of the two types of estrogen receptors, their exact functions, or how they relate to the benefits and risks of our natural estrogen or the estrogen in traditional hormone therapies for menopause.
Nevertheless, recognition of differences in receptors has allowed pharmaceutical companies to manufacture a new class of medicines called selective estrogen receptor modulators (SERMs)—or, to use the more glamorous name, “designer hormones”—that act on one or the other of these receptors to selectively block or stimulate estrogen-like action in various tissues.
One of the first SERMs to be developed was tamoxifen. Known by its trade name Nolvadex and also available as a generic, tamoxifen is prescribed to treat breast cancer and prevent its recurrence in women with a history of the disease and to prevent its development in women at high risk. In the breast, tamoxifen acts as an antiestrogen by binding to the alpha receptor, thus preventing estrogen from accessing it. In other parts of the body, however, tamoxifen acts like estrogen. Another SERM, raloxifene, known by its trade name Evista, is approved for prevention of bone thinning in women after menopause and is being studied as a way to prevent breast cancer. In a recent “head-to-head” trial, raloxifene and tamoxifen provided similar protection against breast cancer but raloxifene had fewer risks. Both of theseSERMs increase hot flashes and the risk of blood clots, however. In the future, watch for additional developments with SERMs, which could eventually be designed to ease symptoms of menopause and protect bone and heart health without adding to the risk of breast cancer.
As with estrogen, receptors for progesterone also come in at least two forms. However, even less is known about their precise roles and functions, or how this information could be used to develop safer or more effective forms ofhormone replacement therapy.
In addition to estrogen and progesterone, generally known as the female sex hormones, the ovaries, along with the adrenal glands, produce small amounts of male sex hormones known as androgens, including testosterone. Testosterone levels in women are only one-tenth as high as in men. Androgens are thought to work in concert with estrogen to maintain a woman’s sex drive, bone and muscle health, energy level, and psychological well-being. Indeed, androgen receptors are found in many of the same cells that have estrogen receptors.
Interestingly, a large proportion of the androgens produced by the ovary and adrenal gland are converted to estrogen by an enzyme called aromatase found in fat and muscle. (Other organs that contain aromatase include the brain, hair, skin, and bone marrow.) After menopause, this conversion actually represents the main source of estrogen in women. Because aromatase is found in fat cells, women who are overweight or obese tend to have higher levels of estrogen than thinner women.
At the same time, because muscle cells are also rich in aromatase, women with more muscle mass are more likely to have higher estrogen levels than their scrawnier counterparts. This is thought to be why heavier women, and women who keep their muscles active with physical activity, may be less likely to suffer from certain symptoms of menopause.
In recent years, medicines called aromatase inhibitors—anastrozole (Arimidex) and letrozole (Femara)—have been approved to treat women with early-stage breast cancer. These medicines work by blocking the aromatase enzyme, thus preventing the conversion of androgens to estrogen in fat, muscle, and other tissues. Together with tamoxifen, aromatase inhibitors form a powerful new arsenal to fight breast cancer. (Not all breast cancer cells have estrogen receptors, though. These medicines stifle the growth of breast cancer cells that have estrogen receptors but do not affect the growth of breast cancers that lack estrogen receptors.)


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