More Questions Than Answers When Managing HIV and Menopause

Note: In this article, “women” refers to ciswomen — those who identify as women and were assigned female sex at birth. Menopause also affects transmen and nonbinary people, but published research on the menopause experience has included only ciswomen participants.

Gina Brown was boarding an early morning flight in 2016 when suddenly she started to overheat. “As soon as I stepped on the plane, I immediately was drenched in sweat,” she said. Not knowing what to do, she stood still until a fellow female passenger noticed her alarm and asked a flight attendant to grab her a cup of ice. “Is this the first time this has happened to you?” the woman asked, and Brown nodded. “It’s called a hot flash,” the woman continued, “and you’re going to be okay.”

As soon as Brown returned from her trip, she visited her doctor for blood work and learned that that her hormone levels were decreasing. “I knew something was going on, but [my provider and I] didn’t have a conversation about menopause,” she said. Brown, who 56 years old, has been living with HIV for nearly 28 years, and is part of a growing group of women with HIV now entering menopause.

In 1996, a person diagnosed with HIV at 20 years of age could expect to live only to age 39. Because of antiretroviral therapy (ART), an HIV diagnosis is not nearly so dire. Now, someone with HIV who adheres to their ART regimen is estimated to have a lifespan close to that of the general population.

For women with HIV, this means going through menopause. Though this transition can be challenging for any woman, experiencing menopause with HIV adds another level of complication. On top of adhering to daily ART regimens, they must also deal with the hormonal changes of menopause and the symptoms that come with it. And the limited research in this area suggests that women with HIV and their clinicians may not be prepared.

“Those of us long-term survivors who have been around for a while never expected to be here, and I don’t think providers or the healthcare system expected us to be here,” said Vickie Lynn, PhD, MSW, MPH, 56, who has been living with HIV for 37 years and received an AIDS diagnosis in 1991. Her work focuses on healthcare interventions for people with HIV. “So now that we’re here, I don’t know that we have enough information or research to inform some of our treatment options.” Instead, these women are met with a series of unknowns due to limited studies and conflicting findings.

Earlier Menopause?

The onset of menopause can be difficult to determine in women living with HIV, said Sara Looby, PhD, ANP-BC, a researcher at Massachusetts General Hospital in Boston and an assistant professor of medicine at Harvard Medical School. Her research focuses on metabolic disorders, including bone loss, cardiovascular disease risk, and menopause in women living with HIV. This population is at an increased risk for amenorrhea (missing menstrual periods), due to both behavioral and clinical factors, and sometimes this amenorrhea is mistakenly assumed to be menopause, she explained. A history of smoking, low weight, methadone use, or use of other psychotropic medications are common in women with HIV and can lead to missed periods. Some factors specific to HIV — including a low CD4 count and a history of an AIDS diagnosis — have also been linked to amenorrhea.

This is likely why research studies on the age of onset of menopause with women with HIV can reach conflicting conclusions. Some studies suggest that women with HIV tend to go through menopause 3 to 5 years earlier than women without HIV. Other studies suggest no difference in the age of onset in menopause between women living with and without HIV. But how menopause status has been accessed can vary from study to study, Looby said. Future research needs to consider participants’ complete menstrual and reproductive history, as well as relevant medical, social and behavioral factors, she added, so that the findings are reliably capturing the age of onset of menopause rather than amenorrhea from other causes.

If menopause does occur earlier in women with HIV, there could be additional health implications. Estrogen regulates bone mass, and some research suggests the hormone may be cardioprotective. Estrogen is also thought to increase production of the neurotransmitter serotonin, which could affect mood and cognition. Women with HIV are already at higher risk for bone loss, cardiovascular disease, and depressed mood compared to women without HIV, Looby said, and as estrogen levels fall during menopause, these conditions may be deleteriously affected.

“If it is determined that women with HIV experience menopause at an earlier age, maybe early to mid-40s instead of 51 and older, they may be at increased risk for cardiovascular and bone conditions as well as mood symptoms associated with estrogen loss at an earlier age than women without HIV, which could be highly detrimental to their physical and mental health,” Looby said.

More Frequent and Severe Menopausal Symptoms?

Women with HIV may not only go through menopause earlier than women without HIV, but their symptoms may also be more frequent and more severe. In a 2017 study of both HIV-positive and HIV-negative Nigerian women, participants with HIV had more menopause symptoms overall and were three times as likely to report severe symptoms compared to women without HIV. A 2005 study conducted in New York found HIV-positive women were 24% more likely to report menopause symptoms compared to HIV-negative women in the study.

Looby’s own research has also found a similar pattern. In a study comparing 33 women with HIV to 33 women without HIV — all were close to menopause and matched for age, race, body mass index, and menstrual patterns—women with HIV reported more severe hot flashes and more days with hot flashes. These women also reported that their hot flashes interfered to a much greater degree with daily activities and quality of life compared to participants without HIV.

But studies of women with HIV who are entering menopause are rare, and most include only small numbers of women. As a result, many women with HIV do not know what to expect entering menopause. “I always say, ‘I wish somebody would do some real research on HIV and menopause, because I want to know if it is worse for us or if it is same,” said Brown, who works as the director of strategic partnership and community engagement at the Southern Aids Coalition in Powder Springs, Georgia. “I would think it’s worse for me.”

More frequent and severe symptoms can have downstream effects, with some evidence suggesting that women with HIV who experience severe menopause symptoms are less likely to stick to their ART regimen. “There’s a clear picture emerging that menopausal symptoms in this group really matter,” said Shema Tariq, PhD, FRCP, a HIV physician-scientist at the University College London Institute for Global Health in England. “They really impact women’s well-being, as well as impacting their ability to look after their long-term condition.”

Providers Are Wary of Treating Menopause Symptoms in Women With HIV

The little research we do have about women with HIV experiencing menopause suggests that this population could greatly benefit from treatment prescribed in women without HIV for menopause symptoms and conditions, including hormone replacement therapy (HRT). Women with HIV regularly experience night sweats and hot flashes during the menopause transition and may have more severe symptoms than women not living with the virus. If women with HIV also frequently enter early menopause (entering menopause before the age of 45), then this group meets two indications for hormone replacement therapy.

Despite the potential benefits of HRT in this population, some studies suggest this intervention is underutilized. In Tariq’s Positive tRansItions through Menopause (PRIME) study, which explores how menopause affects more than 800 women living with HIV, only 8% of respondents reported using HRT. In a Canadian study that has not yet gone through peer review, 11.8% of perimenopausal and postmenopausal women reported ever using HRT, about half the rate of women in North America without HIV.

Provider discomfort with managing menopause-related care in women with HIV is one reason for such low HRT use in this population, Tariq said. In a survey of 88 general practitioners in the United Kingdom, nearly all (> 95%) respondents said they were comfortable managing menopause in a general population, but just 46% said they felt comfortable managing menopause in women with HIV. Their top concerns included the potential for drug-to-drug interactions between ART and HRT, missing an HIV-related diagnosis, and risks of menopausal hormone therapy in HIV. Nearly half of respondents (46%) said only specialists should be providing menopause-related care for women with HIV.

But specialists may also feel conflicted about managing menopause-related care in women with HIV, said Tariq. “If you’re looking at people who manage HIV, you’re looking primarily at infectious disease physicians and HIV physicians. We’re not trained as gynecologists. We’re not used to prescribing HRT,” she said. “And the problem is gynecologists aren’t used to managing HIV. They get nervous about prescribing anything when they see antiretroviral medication because all that people think of is a drug-drug interaction.”

This leaves women with HIV seeking care and treatment for menopause in a difficult situation, where they are “just being ping-ponged around between different healthcare providers,” said Susan Cole-Haley, 53, an HIV-activist in London who has been living with the virus for 23 years. “So many women with HIV have multiple health conditions and multiple healthcare providers, which can just make it really problematic and really exhausting in terms of getting help.”

Many Unknowns

Providers may also be uncomfortable with prescribing hormone therapy because of alarming research in the early 2000s which found that hormone replacement therapy increased the risk of breast cancer and cardiovascular disease. Later analyses have found no increased cardiovascular disease risk in women who were younger than 60 or were less than 10 years beyond the onset of menopause. Still, the “media frenzy” around the initial findings “has put off a whole load of patients and a whole load of clinicians from even thinking of HRT,” Tariq said.

Providers may be even more hesitant because people with HIV already have a higher risk for heart disease, both due to behaviors like smoking as well as HIV-specific factors. (Research has yet to tease out whether these cardiovascular effects are a result of the virus, a result of the antiretroviral therapy, or a result of both factors.) In addition, there have been no prospective studies looking directly at the efficacy and safety of hormone replacement therapy in women with HIV, so providers generally rely on the guidelines for the use of menopausal hormone therapy for women without HIV. While researchers from Canada and the United Kingdom have compiled recommendations for HRT in women with HIV, there is great need for a large-scale clinical trial to establish consistent guidelines for the use of HRT for women with HIV globally, Looby said.

There are also hormonal preparations and drug-to-drug interactions to consider, though none of the interactions identified so far rise to the level of contraindications. Because of how the liver metabolizes ART and HRT, hormone doses may need to be adjusted, or perhaps administered transdermally via a patch versus a pill form. (Estrogen delivered via skin patch may have reduced cardiovascular disease risk compared to other methods of delivery, some studies in women without HIV suggest.) These expected interactions are based on data from contraceptives, noted Elizabeth King, MD, whose research at the Women’s Health Research Institute at BC Women’s Hospital in Vancouver, Canada focuses on menopause and HIV. Studies have not been done on drug-drug interactions between ART and HRT specifically, she said, and formulations for HRT are a bit different from contraceptives.

While these unknowns do need to be discussed in shared decision-making around starting HRT in women with HIV, they should not dissuade providers from considering the treatment, King said. “If women are having extremely troublesome symptoms, then withholding therapy that is potentially beneficial because of worries about some of the things we do not know — I don’t know if that is any better,” she said.

Many women with HIV may not want to start HRT — as was the case for Lynn. “I’ve taken a lot of medication in my time, and I really try to avoid it as much as possible,” she said. Uncertainties around drug interactions were the main concern for Dawn Averitt, 53, founder of the Well Project, an HIV nonprofit focused on women and girls. Averitt has lived with HIV for 34 years. “What if some of the things that I’m dealing with could be managed by HRT?” she said. “Or what if taking it exacerbates problems in a way that nobody knows to look for?” In this case, providers may work with patients to discuss nonhormonal treatment options for menopause symptom management.

While some women with HIV may not want HRT, “It’s important that women have that option, and from what we are seeing right now, not a lot of women are even being offered the therapy,” King said.

There are also other nonhormonal treatments available for managing menopause symptoms, including selective serotonin reuptake inhibitors (SSRIs) as well as nonmedicinal interventions such as cognitive behavioral therapy, but these also have not been studied specifically in women with HIV.

The Path Forward

Tariq and Looby agreed the next step in expanding our knowledge around HIV and menopause should be to better engage women with HIV in research and clinical care around their experience with menopause. This includes studies on the symptoms they regularly experience and how these symptoms affect their quality of life, including their physical, psychological, cognitive, and social health. These studies could also help researchers and clinicians understand what these women with HIV want for their menopause care, whether that be medication, psychotherapy, and/or peer support groups. These interventions, whether pharmaceutical-based or not, can then be assessed based on outcomes in women with HIV, Tariq noted.

Another important factor is increasing education, on both the patient and provider side, Looby said. Many women may not know what menopause is, what symptoms look like, and how these hormonal changes can affect their health. If providers keep an open dialogue with female patients around menopause throughout their adult care, that can better prepare women for the menopause transition and alert them to common symptoms they may experience. There also is a great need for provider education, Looby added. Infectious disease specialists may need further education on menopause management, while women’s health specialists may need additional training for managing care for patients with HIV. Ideally, this information could be shared among a team of providers, including infectious disease, primary care, and women’s health specialists, so that clinicians can collaborate in prescribing treatment for women with HIV Looby said.

Lastly, there needs to be more research funding allocated toward answering questions related to menopause and HIV, including the age of onset of menopause in women with HIV, the severity of symptoms, how HIV may influence the menopause transition and vice versa, and regarding the effectiveness of treatment — pharmaceutical and nonpharmaceutical  — for women with HIV going through the menopause transition. “If we don’t have funding for these studies, then we won’t have answers to establish clinical care guidelines necessary to support the health, well-being, and quality of life of women with HIV,” Looby said.

And the number of women living with HIV entering menopause is expected to keep growing, King added. “It was only a couple of decades ago when women were being told they wouldn’t even live to experience menopause, and now we are at a point where this is the highest proportion of menopausal women ever that we have seen in our HIV clinics,” she said. “It speaks to the success of antiretrovirals,” King acknowledged, but that also means identifying new challenges and addressing recognized gaps in care.

“We are charting a new course, in some ways,” she added. “There is a lot of work to be done.”

For more news, follow Medscape on Facebook, Twitter, Instagram, and YouTube.

Source: Read Full Article