Balancing the Benefits and Risks of Menopausal Hormone Therapy

New studies changing previous perceptions of risk

A woman receives counseling from her provider via telehealth

For the right woman with the right history at the right time, menopausal hormone therapy can be beneficial for quality-of-life issues as well as mitigation of some disease risks. But how can providers best counsel their patients on whether or not to start therapy in light of conflicting and sometimes controversial studies in the literature?

According to Anna Camille Moreno, DO, family medicine physician and assistant professor in the Department of Obstetrics and Gynecology, the answer is highly individualized and based on each patient’s personal needs and risk factors.

“When patients ask me about hormone therapy, I ask a lot of questions myself to help stratify their risk factors,” says Moreno. In addition to questions about past pregnancies and birth control methods, her questions include:

  • Do you have troublesome vasomotor symptoms?
  • Do you have bothersome vaginal and urinary symptoms pertaining to vaginal atrophy?
  • Have you recently received a new diagnosis of anxiety or depression?
  • Do you have a history of breast, endometrial or uterine cancer? Is there a family history of breast cancer in your family?
  • Do you have active or chronic liver disease?
  • Do you have gallbladder disease?
  • Do you have fibrocystic breast disease?
  • Do you have uterine fibroids?
  • Have you ever experienced blood clots in the veins of legs or in the lung? This includes blood clots during pregnancy or when taking birth control pills.

Moreno, whose interdisciplinary women’s health practice focuses on mid-life care, including menopause, perimenopause, hormone therapy, and associated medical issues, points to the 2002 results from the landmark Women’s Health Initiative (WHI) as the starting point for many physicians when counseling patients on risk factors.

The WHI results indicated that post-menopausal women taking combination (estrogen and progestin) hormone therapy for menopause symptoms had an increased risk for breast cancer, heart disease, stroke, blood clots, and urinary incontinence. Although women had a lower risk of fractures and colorectal cancer, these benefits were not found to outweigh the risks. As a result, many women stopped taking hormone therapy.

Although the WHI was a groundbreaking study, Moreno notes that it’s important to understand the context of the findings. For example, she says, the average age of WHI participants was 62.5 when they started the hormone therapy, which is significantly older than the average age of 51 for menopause onset. Subsequent secondary analyses demonstrated that risks were influenced by a woman's age and time since menopause, with lower absolute risks and hazard ratios for younger women than older women.

“The WHI report is still often used to inform patient care,” she says, “but newer studies are changing perceptions. Several recent studies suggest hormone therapy decreases overall all-cause mortality, with women living longer within 10 years of initiated therapy. There’s also an overall decreased risk of cardiovascular disease, dementia, and fractures, as well as colon, uterine, and ovarian cancer. So for the right individual at the right time, hormone therapy can be safe and effective. Our job as physicians is to address a patient’s need for it and counsel them on outcomes and benefits, not just the associated risks.”

For women who are unable to take hormones because of hormone-sensitive cancers or other risk factors, Moreno says nonhormonal options are improving, but cautions that only FDA-approved medications should be prescribed, and providers should counsel patients to avoid anti-aging clinics that prescribe non-regulated hormones.

Some of the newer options include:

  • Paroxetine, a selective serotonin reuptake inhibitor
  • Desvenlafaxine, an antidepressant in the class of selective serotonin and norepinephrine reuptake inhibitors
  • Fezolinetant, a small-molecule, selective neurokinin-3 receptor antagonist currently in phase 3 clinical trials

Moreno encourages physicians to be proactive when counseling women in their mid-life years. “With all of the recent studies and available data, I think it’s an exciting time to not just discuss menopausal and perimenopausal symptoms with patients, but to address them. We shouldn’t ignore symptoms or wait five years for them to possibly improve when we can help improve a woman’s quality of life and possibly help prevent disease with the right hormone therapy.”