A Cautious View of Menopausal Hormone Therapy

In the ’80s and ’90s, when Mary Hunter (BSN ’80, post-master’s ANP ’11) was working as a women’s health nurse practitioner, she was bombarded with information on what was called “hormone replacement therapy” (HRT). She attended conferences sponsored by pharmaceutical companies, read a never-ending flow of promotional literature and frequently saw drug reps in the gynecology clinics where she worked, all touting the supposed benefits of estrogen.

It was the heyday of HRT – now generally referred to as HT – and an estimated 38 percent of menopausal women were taking it by the early 2000s.

“HRT was promoted to extend life and prevent disease, and there was always a strong implication that it had antiaging effects,” Hunter says. “I was under a lot of pressure by the gynecologists who employed me to prescribe menopausal hormone therapy for almost everybody who was perimenopausal or older.” She became concerned that the promotional materials were glossing over potential risks, particularly for long-term use. Her interest piqued, she became determined to look more closely at HT and the reasons so many women were using it.

Landmark Studies Show Risks of HT Use

Hunter’s concerns turned out to be warranted. Despite early hopes that HT would be protective against some of the diseases of aging, results of large, longitudinal studies published in the early 2000s, including the Heart and Estrogen/Progestin Replacement Study (HERS) and the Women’s Health Initiative (WHI) in the US, and the Million Women Study (MWS) in the UK, suggested that HT was associated with increased risk for a variety of conditions. These and subsequent studies linked the use of estrogen alone or in combination with progestin to increased risk for cancers of the breast, ovaries and endometrium; stroke, blood clots, gallbladder disease, dementia and incontinence. Risks increased with long-term use.

Based on these findings, the American Congress of Obstetricians and Gynecologists (ACOG), now recommends that HT “should be limited to the treatment of menopausal symptoms at the lowest effective dose for the shortest amount of time possible,” while acknowledging that decisions on HT must be made on an individual basis between a woman and her provider. And in 2003, the Food and Drug Administration (FDA) recommended (but did not require) that manufacturers of estrogen and estrogen-with-progestin products for treatment of menopausal symptoms update their product labeling to reflect findings on HT-related risks.

A complete understanding of those risks and how they affect different groups of women remains elusive, however. A series of studies published since the first release of the HERS, WHI and MWS findings suggest that the risks for some conditions may be different for different subgroups of women, depending on a number of factors, including when after menopause HT is initiated, how long it is used and what kind of therapy is prescribed.

All of this has resulted in a plethora of seemingly conflicting news stories and differing opinions among experts and clinicians about when to start HT, how long to continue it and whether to use it at all. Science is, of course, an iterative process, and all the uncertainties and nuances can make it difficult for women to make a decision about HT, but many seem to have eschewed it. By 2009, the prevalence of use ranged from 12.9% in women aged 55 to 60 to 3.9% in women over age 75.

Concerns over Length of Use

Nevertheless, Hunter remains concerned that some of these reports are giving women a false sense of security about HT, and that researchers aren’t paying adequate attention to the risks of using it over the long term.

She notes that women in the oft-cited WHI studies were exposed to hormones for less than five years, while many women stay on it for longer. “WHI’s risk calculations are based on limited duration of use,” she says. “I think the MWS is more instructive because those study data reflect long-term use.”

These distinctions are important, Hunter says, because statistics derived from the WHI are often cited by those who argue that the dangers of menopausal hormone therapy are minimal. She cites the example of the 2006 WHI finding that estrogen-alone therapy was not associated with increased risk for breast cancer. While that study is often used to reassure women, Hunter believes that reassurance is inappropriate when estrogen is prescribed for longer than five years.

It’s a significant concern, because it appears that, despite the overall decline in HT use and trends toward lower-dose therapy (which Hunter notes has not been shown to reduce risks), the length of use appears to be creeping up. A 2012 study by Kaiser Permanente researcher and UCSF clinical professor of medicine Bruce Ettinger found that the average length of HT use rose slightly but steadily between 2002 and 2009.

Asking Women Why They Choose Long-Term HRT

Because decisionmaking around HT affects a lot of women – the 2010 census put the US population of women aged 40 and older at more than 75 million – Hunter wants to know why some choose to use it, particularly over the long-term, despite the consensus that longer use raises the risks.

In 2012, she returned to the UC San Francisco School of Nursing to pursue a doctorate and to look at the phenomenon in a structured way. For her dissertation, she is interviewing women over age 60 who have been using systemic estrogen for more than five years. While most cite hot flashes as a primary reason to use estrogen, Hunter says it’s unclear if that’s the whole story.

She wonders if some women remain on HT longer in part because they believe they’re benefiting from it cosmetically. She notes that, when asked, some of her research subjects say that people tell them they look younger than their age, although they assert they don’t take HT primarily for that reason. This observation is particularly interesting, says Hunter, because it reflects a widespread misperception about estrogen’s effect on skin.

She says, “I find it fascinating that, while sharing my research interest in social settings, even among nurses, someone will usually say, ‘Well, doesn’t estrogen keep your skin looking young?’ But the evidence doesn’t support it.” Hunter also notes that her interviewees have reported that using estrogen helps them maintain other youthful attributes such as physical strength and dexterity, enjoyment of sex and a zest for life.

Proceeding with Caution

While she hopes her current research will eventually shed some light on women’s motivations for how and why they use HT, she also wants to ensure that women and clinicians are informed about the risks as we currently understand them. She advises women to remain cautious when looking at reports in the media and at the research itself.

She cites medical ghostwriting – pharmaceutical companies employing marketing firms to author articles for publication in medical journals under the names of notable physicians – as one example of how consumers and clinicians can be misled. Deceptive article titles and abstracts are another way research can be distorted to fit a particular point of view, she says.

“Be suspicious,” Hunter cautions. “Look for connections between opinions expressed, research reports and possible drug company involvement.”