Combination Therapy

Night sweats. Hot flashes. Depression. Brittle bones. All of these debilitating symptoms have been linked with HIV disease, its treatment, or the ongoing physical and psychological burden of fighting the chronic illness. But these ailments also are common symptoms of menopause, the natural process during which women cease menstruating. For HIV-positive women in their late 40s to mid 50s'when the first signs of menopause are most likely to arise, according to the National Institutes of Health'the combination of the two conditions can be confusing, overwhelming, and unfortunately often left unaddressed by their health care providers, says Susan Cu-Uvin, MD, director of Miriam Hospital's Immunology Center in Providence, R.I. Cu-Uvin and her colleagues, however, are working hard to reverse that trend through the center's HIV Menopause Clinic. Believed to be the nation's first devoted to HIV-positive women, it offers caregivers and their patients a unique opportunity to focus on a medical issue that too often is pushed to the back burner during routine HIV checkups, says E. Milu Kojic, MD, the clinic's director. But as HIV-positive women live longer lives with successful antiretroviral therapy, conditions related to the natural aging process, like menopause, are going to become more prominent and demand more attention, she says. 'The median age of women in our HIV clinic is now 42, and if they are going to live longer, we know they are going to hit perimenopause [when patients may still menstruate, but begin having such symptoms as hot flashes, mood changes, and irregular periods] and menopause,' explains Cu-Uvin, who founded the menopause clinic. 'We realized that talking about menopause during an HIV appointment did not provide time enough to really address the issue.' That is exactly the problem Boston resident Shirley Royster, 57, ran into when she started experiencing menopausal symptoms. Although she suspected her fatigue, mood swings, and irregular menstrual periods were related to the onset of menopause, she was hard-pressed to find time to discuss it with her HIV caregiver'and was unable to get a clear answer when she did. 'I asked whether she thought the issues were caused by menopause or HIV, and she did not know,' says Royster, who has known she is HIV-positive since 1985. 'She could not even guide me to any place where anyone else knew. I would definitely have taken advantage of the menopause clinic if it had existed in Boston; it would have been the first place I would have gone to.' Delving for Data Helping guide HIV-positive women through menopause is only one of the clinic's two major goals, says Cu-Uvin. The other is to gather data about how menopause affects HIV-positive women, interacts with HIV disease and its treatment, and potentially further exacerbates such HIV-related conditions as cardiac risks, bone loss, and depression. To date, virtually nothing is known about the effects of menopause on HIV-positive women, Kojic says. 'The obvious reason for this,' she explains, 'is because in the past there just were not enough HIV-positive women living long enough to have enough numbers to study. But now there are, which makes the clinic even more exciting.' One of the biggest concerns'and most sinister unanswered questions'is whether HIV and menopause will work symbiotically to hasten bone loss in HIV-positive women. 'We know from preliminary data that HIV-infected men and women have lower bone density than people who are not HIV-infected,' either because of HIV disease, its treatment, or both, says Geetha Gopalakrishnan, MD, an endocrinologist who operates the bone center at the menopause clinic. 'And we know that menopause definitely increases the risk of bone loss in women. The combination of the two, one would anticipate, would place menopausal, HIV-infected women at an even higher risk. But no one has really looked at this issue; we are not sure if there are higher risks or not.' Scientific information also is scarce in many other research and treatment areas, Cu-Uvin adds. 'For example, will menopause occur earlier in women with HIV compared to women without HIV? We do not know,' she says. 'When patients ask, 'What kind of symptoms will I have? Will I have more or less?' I do not have the answers for those. But as we collect data and keep track of the patients, maybe we will be able to learn the answers to some of those questions.' Even more serious, potentially, is that it is unclear whether HIV-positive menopausal women place their sex partners at a higher risk for HIV infection through sexual contact, Cu-Uvin says. 'We know that the vaginal lining becomes thinner when you are in menopause,' she says. 'As this thins out, is it easier to experience microtrauma because the mucosa is not as healthy? Do menopausal women shed more HIV than premenopausal women? Would hormone replacement therapy lessen genital shedding? We just do not know the answers to any of these.' Jim Campbell, president of the Boston-based National Association on HIV Over Fifty, which promotes HIV education, prevention, and health care programs for people over age 50, is particularly concerned about HIV infection risks, since studies show most older Americans are sexually active'and rarely practice safer sex. According to an AARP study, he says, 96% of people over 60 who were sexually active said they do not use condoms. If there is an elevated risk of menopausal women passing HIV to their sex partners'or if HIV-negative menopausal women are at a higher risk for HIV infection themselves'there could be exploding rates of HIV among older adults, Campbell warns. 'Already, the incidence of new infections among people over 50 is growing at a rate of one percentage point per year,' he notes. 'It's growing at an alarming rate.' Treatment Uncertainties While there seem to be more questions than answers facing Cu-Uvin and her colleagues at this point, there are some broader issues that should be addressed in all menopausal women, regardless of serostatus, they say. The most prominent of these is whether to use hormone replacement therapy to help prevent bone loss, curtail hot flashes, and control several other symptoms related to the falloff of estrogen production in the body. Several studies released during the past two years suggest that HRT'particularly combination estrogen-progestin therapy but also, to a lesser degree, estrogen supplements alone'can significantly boost the risks for breast cancer, heart attacks, strokes, gall bladder disease, and blood clots. The national Women's Health Initiative study was halted in 2002 after it was shown that women taking estrogen-progestin treatments were at a roughly 25% increased risk of breast cancer. Another large-scale government study of estrogen-only replacement therapy was called off in March 2004 because the hormone boosted risks for strokes and dementia. Research also has shown that combination HRT boosts heart attack risks by nearly 30%. Whether these risks are even greater for HIV-positive women'particularly ones with elevated heart attack risks caused by high cholesterol and triglyceride levels'is unknown. 'Most of our patients are not on HRT, and we are addressing a lot of issues, like osteoporosis, without HRT,' says Gopalakrishnan. 'But when women come into the clinic, we are able to set aside time to talk with them about the risks and benefits of all their treatment options.' This includes addressing the use of over-the-counter products, particularly such herbal remedies as black cohosh, soy supplements, dong quai, wild yam, and scores of others that are recommended by other menopausal women to treat such symptoms as hot flashes and night sweats. Virtually none of these products have been tested in HIV-positive women, and many could react poorly with anti-HIV medications or other drugs used to treat HIV-related conditions, Kojic warns. Research already has shown such commonly used over-the-counter products as Saint-John's-wort and garlic supplements can greatly diminish the effectiveness of antiretroviral drugs. Therefore, all HIV-positive women considering any supplement or herbal remedy should first discuss its use with their physicians, Kojic advises. It is precisely the need for these sorts of in-depth conversations that Cu-Uvin says was the impetus behind the formation of the menopause clinic, which operates the first Thursday of each month and can accommodate 10 to 12 women per session. 'We wanted to have dedicated time and a place where we could talk with women specifically about these issues,' she says. 'I think we are right at the cusp of the future'of bringing much more attention to an issue that has not gotten the attention it deserves.' Royster wholeheartedly agrees. 'Even five years ago people did not think about things like this'or if they thought about them, there was no place to go,' she says. 'This clinic is almost a dream come true. I hope it is just the beginning, and more clinics will be opened, and the issue of HIV in women over 50 will be taken more seriously.'