Should Women Consider Taking Testosterone?

Naomi, 55, a human resources executive in Guttenberg, N.J., had a hysterectomy in her 30s and suffered from hormone depletion for years afterward. "I spent a decade and a half in a fog," she says. "I lost all my sexuality and felt numb at the mere thought of sex. I cried at the drop of a hat and had sweating, pain, swelling and mood swings. My muscles were so weak that I broke my ankle — me, a high-heel wearer."

Fearing the potential side effects, Naomi had resisted estrogen therapy. But then five years ago, when she'd reached a low point and was ready to leave the job she loves, her gynecologist, Dr. Nancy Lebowitz, a clinical instructor at New York's Cornell Medical Center, started her on another form of hormone replacement, which she has remained on ever since.

"Within a week," Naomi says, "the light came back in my life. I felt like a woman of 25. It was amazing. I no longer have those weepy moments or night sweats. I know I sound like an addict, but I'm really not."

Greer, also 55, a pediatric dietician in Dayton, Ohio, received a diagnosis of metastatic breast cancer at age 34. She recovered after chemotherapy, radiation and bone marrow transplants, but was left feeling chronically tired, moody and forgetful, with little interest in sex. Five years ago, Dr. Rebecca Glaser, a local breast surgeon, started her on a treatment, which she continues today, that has improved her mood, memory and libido.

"I feel even-keeled and normal, and my energy level is fantastic," she says. "After so many difficult years, nothing could be better than that."

The therapy in both cases? Testosterone, widely and misleadingly understood to be the "male" hormone. Men produce 10 times more testosterone than women, but in their early reproductive years women have 10 times more testosterone than estrogen coursing through their bodies.

Many experts now believe that it's the loss of testosterone, and not estrogen, that causes women in midlife to tend to gain weight, feel fatigue and lose mental focus, bone density and muscle tone — as well as their libido. "Testosterone is our most abundant biologically active hormone," says Glaser, an assistant clinical professor of surgery at Wright State University's Boonshoft School of Medicine and a leading researcher and advocate of testosterone therapy for women. "Adequate levels of testosterone are necessary for physical and mental health in both sexes."

"Women, before, during and past menopause, and sometimes as early as in their mid-30s, invariably have low testosterone levels," Glaser says. Not all of them will experience its wide variety of symptoms, like low libido, hot flashes, fatigue, mental fogginess and weight gain.

For those who do, and who seek to avoid taking synthetic oral hormones (shown by National Institutes of Health findings to pose an increased risk for breast cancer, heart attack, stroke, blood clots and dementia), bioidentical testosterone (whose molecular structure is the same as natural testosterone) has been shown to be safe and effective.

Some testosterone is converted by the body into estrogen — which partly explains why it is useful in treating menopausal symptoms. For those at high risk for breast cancer, or who have had it, that conversion can be prevented by combining testosterone with anastrozole — an aromatase inhibitor that prevents conversion to estrogen.

Nonetheless, testosterone has been shown to be beneficial for patients with breast cancer. Preliminary data presented at the American Society of Clinical Oncology have shown that, in combination with anastrozole, testosterone was effective in treating symptoms of hormone deficiency in breast cancer survivors, without an increased risk of blood clots, strokes or other side effects of the more widely used oral estrogen-receptor modulators tamoxifen and raloxifene.

Other benefits cited for testosterone therapy include:

• Relieving symptoms of menopause, like hot flashes, vaginal dryness, incontinence and urinary urgency.
• Enhancing mental clarity and focus. Researchers at Utrecht University in Holland recently found that testosterone appears to encourage "rational decision-making, social scrutiny and cleverness."
• Reducing anxiety, balancing mood and relieving depression combined with fatigue. Dr. Stephen Center, a family practitioner in San Diego who has treated women with testosterone for 20 years, says the regimen consistently delivers "improvement in self-confidence, initiative and drive."
• Increasing bone density, decreasing body fat and cellulite, and increasing lean muscle mass. "Testosterone is the best remedy available for eliminating midlife upper-arm batwings," says Dr. George Yu, a urologic surgeon and aging specialist at Aegis Medical and Research Associates in Annapolis, Md.
• Offering protection against cardiovascular events, by increasing blood flow and dilating blood vessels, and against Type 2 diabetes, by decreasing insulin resistance.

Men and women in the United States have used testosterone therapy since the late 1930s, in many instances for more than 40 years — with only rare adverse results. Yet many patients, and doctors, are unaware of testosterone therapy for women. The number of women in the United States currently on testosterone therapy is estimated to be in the tens of thousands — miniscule compared with the millions prescribed oral estrogen-progestin regimens, like Premarin and Provera.

With a growing recognition of testosterone's benefits for women, those numbers may increase, but it may still be a while before the therapy reaches the mainstream. Advocates say that the very idea requires a rethinking of long-held notions about hormones. And many women have a knee-jerk suspicion that any hormone treatment can increase their risk of breast cancer. However, clinical studies show that testosterone not only does not increase a woman's risk of breast cancer, it may play a key role in warding off the disease.

Some women believe, also incorrectly, that testosterone therapy will produce "masculinizing" traits, like hoarseness and aggression. While the hormone may cause inappropriate hair growth and acne in some women, those side effects can be remedied by lowering the dose.

Testosterone therapy has been approved for a variety of conditions in women as well as men in Britain and Australia. But while the U.S. Food and Drug Administration has approved of testosterone for use in men whose natural levels are low, the agency has not sanctioned it for women, for any reason. In 2005, the FDA denied approval for a women's testosterone patch, citing concerns about long-term safety. Similar concerns have been put forth by the North American Menopause Society, although that group has also acknowledged testosterone's efficacy in treating low libido in women.

Doctors, however, have the legal discretion to prescribe testosterone, off-label, to women, as they see fit and often do so to combat fatigue, mental fogginess and low libido. Glaser thinks this will likely remain the status quo for a while, given the prohibitive cost of conducting the long-term safety studies needed to win fuller FDA approval.

Women can take testosterone as a cream, through a patch or in the form of pellet implants, which have the highest consistency of delivery. Synthesized from yams or soybeans, and compounded of pure, bioidentical testosterone, the pellets, each slightly larger than a grain of rice, are inserted just beneath the skin in the hip in a one-minute outpatient procedure. They dissolve slowly over three to four months, releasing small amounts of testosterone into the blood stream, but speeding up when needed by the body — during strenuous activities, for example — and slowing down during quiet times, a feature no other form of hormone therapy can provide.

To determine a patient's dosage, some doctors measure testosterone levels in the blood or saliva, while others make judgments based on symptoms. The problem, Glaser says, "is that testosterone is difficult to accurately measure in women. Levels vary considerably, not only throughout the month, but also during the day, making a single level unreliable."

Side effects of the insertion procedure, which are rare, include infection, minor bleeding and the pellet "working its way out," Glaser says. Once inserted, pellets can't be removed. Some patients notice improvements within a day or two; others do not perceive benefits for a couple of weeks. If symptoms recur, patients can return for re-evaluation.

Pellet inserts cost about $230 to $500. Since testosterone is not FDA-approved for women, though, it is rarely covered by insurers. Advocates call this unfair, because men with sagging libidos are covered, while women seeking treatment for the same condition, to say nothing of breast cancer or heart disease, are not. Testosterone pellets have long been covered for women in Britain.

Since implantation is a surgical procedure, and the pellets are manufactured by a variety of pharmaceutical compounders, who may have varying safety standards, it's important for women to consult with an experienced, board-certified physician about treatment. But while a growing number of gynecologists, family practitioners, urologists and cardiologists, among others, now treat women with pellet implants, there is as yet no national resource to direct patients to vetted doctors who provide this treatment.