For over two decades, many women have approached the transition into menopause with a sense of trepidation, particularly regarding the safety of hormone therapy. This hesitation is largely a legacy of the early 2000s, when high-profile study results suggested significant health risks, causing a dramatic decline in the use of these treatments. However, a major new Danish nationwide study published in the BMJ provides substantial evidence to help modernize this conversation, offering new insight for women navigating midlife health.
Understanding the Findings
Researchers followed nearly 900,000 Danish women for an average of 14 years to determine if menopausal hormone therapy (MHT) influenced long-term mortality. The most significant takeaway is that MHT was not associated with an increased risk of all-cause mortality. In fact, the overall risk (hazard ratio) for mortality among users was slightly lower than for those who never used the therapy.
The study also looked at the duration of use, finding no increased risk even for women who utilized the therapy for 10 years or more. Furthermore, the researchers found no "unequivocal differences" in deaths specifically caused by cardiovascular disease or cancer between those who used the therapy and those who did not.
Why Formulation and History Matter
The research highlighted that the way hormones are delivered may play a role in safety profiles. Women using transdermal formulations (such as patches or gels) experienced a 15% reduction in mortality hazard compared to non-users.
The study also provided critical insights for a specific group of women: those who have had both ovaries surgically removed (bilateral oophorectomy) between the ages of 45 and 54. For these women, hormone therapy was associated with a 27–34% decrease in mortality hazard, suggesting that for this group, MHT may offer a significant protective benefit.
A Shift in Perspective
For years, clinical practice was influenced by the 2002 Women’s Health Initiative (WHI) trial, which primarily studied older women (average age 63) who were often many years past their last period. This new research focuses on a more representative "real-world" population of women starting therapy closer to the onset of menopause.
Insight for the Reader
This evidence supports current guidelines recommending MHT for women with moderate to severe symptoms who do not have specific contraindications. It moves the focus away from a "one-size-fits-all" fear and toward a personalized assessment of benefits (such as the relief of hot flashes, night sweats, and sleep disturbances, ‘brain fog’) against a backdrop of long-term safety.
While this data is reassuring, health decisions remain individual. The findings suggest that long-term use is not the "red flag" it was once considered, but rather a manageable part of a woman’s health journey in her 40s, 50s, and beyond.
Mode of use:
In this nationwide cohort study, transdermal hormone therapy (delivered via patches or gels) demonstrated a more favorable safety profile regarding long-term mortality than oral formulations (tablets).
The primary differences identified in the sources include:
Mortality Hazard: Transdermal therapy was associated with a statistically significant 15% reduction in the hazard of all-cause mortality compared to women who never used hormone therapy (Adjusted Hazard Ratio (aHR) 0.85). Conversely, oral formulations showed no significant difference in mortality hazard compared to non-users (aHR 0.98).
Incidence Rates: The incidence of death was lower among transdermal users, at 42.9 deaths per 10,000 person-years, compared to 57.7 deaths per 10,000 person-years for those using oral formulations.
Usage Prevalence: Oral therapy was the most common method used by the participants. Specifically, tablets containing estradiol and continuous norethisterone acetate were the most frequent, accounting for 32.3% of all menopausal hormone therapy used in the study.
The researchers noted that these findings align with and support current clinical guidelines, which suggest that transdermal therapy is associated with the lowest all-cause mortality among women starting treatment. While oral therapy was not linked to an increased risk of death, it did not demonstrate the same significant survival benefit as the transdermal options.
It is important to note that this was an observational study; therefore, it identifies associations but does not confirm causality.
Norwegian version of the article is available here. You can read more about Menopause symptoms here.
Source:
1. Mikkelsen AP, Bergholt T, Lidegaard Ø, Scheller NM. Menopausal hormone therapy and long term mortality: nationwide, register based cohort study. BMJ. 2026 Feb 18;392:e085998.
