Hormone Therapy for Prevention Requires a Nuanced Approach

Should physicians be prescribing hormone therapy (HT) to help prevent certain chronic health conditions for people who are post-menopausal? Holly Thacker, MD, FACP, director of Cleveland Clinic’s Center for Specialized Women’s Health, believes there may be a good case for doing so with some patients.

The first steps, however, should be a physical exam, a careful assessment of when the patient entered menopause, and a conversation that explores the potential risks and benefits of hormone therapy, especially for younger patients and those who have been in menopause less than 10 years, says Dr. Thacker.

Potential therapies include:

• Estrogen only for patients who have had the uterus removed.
• Combination therapy (estrogen plus progestin) for those with a uterus. Estrogen stimulates endometrial proliferation, which can be linked to uterine cancer. Progestin mitigates the stimulating effects of estrogen on the endometrium.

Patients experiencing symptoms of menopause such as hot flashes and vaginal dryness should be counseled on HT for symptom relief – a conversation that may require physicians to dispel fears rooted in 20-year-old headlines about HT.

In addition to symptom relief, however, Dr. Thacker says appropriately prescribed HT for some patients who are younger or who are earlier in menopause may decrease their risks of some chronic conditions, including osteoporosis and bone breakage, cardiovascular disease, diabetes and dementia. And for women who take HT in their 50s, studies have shown a reduction in overall death rates.

For younger women and those who have more recently entered menopause, replacing estrogen for five to 10 years may protect overall function and quality life, says Dr. Thacker.

“Many menopausal experts, including myself, believe that we should be discussing the preventive aspects of hormone therapy,” Dr. Thacker says. “This can be challenging, because we are talking about a preventive treatment that can stimulate the breast and uterus, presenting some risk for cancer, and that in a small percentage of people increases risk of blood clot.

“But I think that women should be counseled that there’s a window of time during which hormone therapy may offer the best potential cardiovascular benefit and potential brain benefit,” she adds.

The impact of research, interpretation and the media on patient care

The history of menopause and its treatments has been punctuated both by information droughts and headline-grabbing controversies. Critical to the latter were the initial results and interpretations of a hormone therapy trial by the Women’s Health Initiative (WHI) begun in 1998, which shocked the public and planted fears that still linger today in some circles.

The WHI was the largest and most expensive trial in the history of the United States to look at primary prevention and menopausal hormones in women. The research included women ages 50 through 79.

“Prior to the WHI, there was much observational data that really strongly suggested that hormone therapy dramatically reduced many diseases and improved longevity,” Dr. Thacker says.

In 2002, the first results were published. Among participants with uteri (who received combination therapy), increased incidence of heart disease and breast cancer were observed alongside a reduction of colorectal cancer and osteoporotic bone breaks. That part of the trial was discontinued, generating headlines that reverberated among clinicians and patients alike.

Two years later, results of the estrogen-only portion of the study showed increased risk for stroke, and that arm also was discontinued. That, too, amplified fear of HT.

These original announcements did not include age-stratified data, which had an impact on interpretation of results. “It was a very scientific study, but somewhat unscientifically interpreted, and it affected a whole generation of women,” Dr. Thacker says.

Later analysis of the WHI trial demonstrated HT in women 50 to 59, or who were with 10 years of the onset of menopause, had beneficial cardiovascular effects and a reduction in all-cause mortality.

In spring of 2022, the U.S. Preventive Services Task Force release its draft recommendation regarding hormone therapy for the primary prevention of cardiovascular diseases, cancer and osteoporosis and bone disease. The draft reaffirms its 2017 recommendation against the use of hormone therapy for prevention of chronic conditions, by either patients with or without a uterus.

Still, Dr. Thacker believes it’s important for physicians to discuss risks, benefits and alternatives with their patients, some of whom may choose HT.

“When the WHI eventually gave us age-stratified data, it showed a 30% reduction in death rate for younger women taking HT,” she says. “There’s nothing else that we use for primary prevention that has any mortality benefit, whereas hormone therapy does.”

In addition, she adds, HT is correlated with better work productivity.

“From an economic standpoint, a longevity standpoint and a quality-of-life standpoint, many women benefit. And especially estrogen alone in patients with hysterectomy: It should strongly be considered for prevention, because where there is no uterus, there are no negative uterine effects,” she adds. “As long as the person doesn’t have active deep vein thrombosis, or you use transdermal estrogen, it’s really just all upside except for the minimal cost of the medicine.”

Most people will benefit, she says, but not everyone will. Still, she adds, patients must have choices and options.

“My goal medically is to get five to 10 years of hormone therapy in most women who are open to it and don’t have risk of blood clot,” Dr. Thacker says.

Advice for clinicians

From a longevity perspective, cardiovascular health, bone, sexual function, sleep and mood are positively influenced by estrogen.

In Dr. Thacker’s practice, preventive use of estrogen alone is considered for any hysterectomized woman under age 60, and potentially older, depending on when they entered menopause. Physicians should be comfortable in prescribing a transdermal estrogen patch to a woman who doesn’t have a uterus or an endometrium, she adds.

Accurately ascertaining the patient’s age of onset of menopause is key. This can be difficult to determine, and goes beyond identifying the date of the last menstrual period.

“It might have stopped because they had an IUD or an ablation,” she says. “Maybe they had a hysterectomy but still have ovaries. It is critically important to know the age of menopause.”

HT may be considered even for menopausal patients who haven’t suffered from typical symptoms, because they may be experiencing other effects from estrogen deficit. “Half of women lose bone, and 80% of women eventually have significant changes to their vagina, urethra and the base of the bladder,” Dr. Thacker says. “One in two women have overactive bladder, bladder leakage or bladder infections.”

Dr. Thacker recommends that physicians who don’t feel comfortable prescribing HT should refer interested patients to physicians who are willing to have the conversation.

“Patients are very appreciative when they improve, either because their doctors treat them directly or refer them to someone who will,” she says. “In women’s health, we’re all about empowering women, but in order to empower them, you have to give them accurate information.”