• Menopause involves distinct changes in hormone levels and bodily functions.
• Using hormone therapy can help relieve some symptoms related to menopause. Experts want to find out all the risks and benefits of using hormone replacement therapy.
• Data from a recent trial suggest that short-term hormone therapy for menopausal symptoms does not have long-term cognitive effects, either harmful or beneficial.

Menopause involves the definitive cessation of menstruation. There is a distinct drop in estrogen that occurs at menopause.

An article recently published in PLOS Medicine reported data from the Kronos Early Estrogen Prevention Study (KEEPS) continuation study.

Researchers found that compared to placebo, women who received hormone treatment for menopausal symptoms did not experience better or worse cognitive outcomes 10 years after treatment.

The results suggest that short-term menopausal hormone therapy is not harmful to cognitive function, but also does not appear to provide cognitive benefits.

The researchers wanted to learn more about the long-term effects of short-term hormone therapy. They note that this type of therapy is used close to the menopausal transition period. The transition period before the last menstruation is sometimes called perimenopause.

The research discussed in this article involved women who participated in a previous study called the Kronos Early Estrogen Prevention Study (KEEPS). This original research focused on healthy people, recently postmenopausal women with a weak cardiovascular disease risk who had an intact uterus.

Women participating in the original research received a placebo, a transdermal patch estradiolor orally conjugated equine estrogens. Participants receiving these hormonal options also received progesterone. The original study continued for 4 years.

The results of the current article discuss the results of the KEEPS continuation study, which followed participants approximately 10 years after the original study ended. A total of 275 participants had data related to cognitive outcomes from the original study and the KEEPS study.

For the KEEPS study, researchers collected data on medical history, mood, and cognitive outcomes. They also conducted several cognitive tests to examine participants’ memory, mental flexibility, and visual and auditory attention.

The KEEPS study also noted which participants had continued or used another menopausal hormone treatment since the original study ended.

Results from the KEEPS study revealed similar cognitive outcomes in women who received placebo or hormone replacement therapy in the initial trial.

Participants’ baseline data in the original study and their performance throughout the original study were better indicators of cognitive function at long-term follow-up.

Thus, the results suggest that the use of hormonal therapy in early menopause does not affect long-term cognitive function in women at low risk of cardiovascular disease.

Overall, the data contribute to a better understanding of the relationship between short-term menopausal hormone therapy and cognitive function.

G. Thomas Ruiz, MDa board certified OB-GYN and principal OB-GYN at MemorialCare Orange Coast Medical Center in Fountain Valley, California, who was not involved in this study, commented on his findings at Medical news today:

“This study looked at cognitive effects differently than many papers. Most studies approach the issue from the perspective that HRT (hormone replacement therapy) improves cognitive abilities. No study has definitively demonstrated this. But it’s good to know that there are no negative cognitive effects when using HRT either. It should be noted that long-term HRT is linked to a lower risk to develop Alzheimer’s disease.

The data has some limitations. First, the follow-up study included only a fraction of the women in the original study.

However, the researchers were able to include baseline data from these “non-participants” to help examine differences between groups. The researchers acknowledge that there may be a risk of healthy survivorship bias regarding participants who chose to participate in both studies.

KEEPS study researchers were unable to fully examine all of the effects of the lower number of participants in the KEEPS study, such as the cause of death for nonparticipants. The KEEPS study also faced challenges related to the COVID-19 pandemic.

Second, the original study had specific inclusion criteria that limited the scope of the data. For example, this excluded women with uncontrolled high blood pressure or who smoked. The average age of the participants was also 52, and the researchers only included women with a low risk of cardiovascular disease.

Additionally, most of the population studied in the KEEPS study was white. Thus, the results cannot be generalized and greater diversity might be useful for future research.

Some data relied on participant self-report, which is not always reliable. The researchers used self-reported age rather than age data from the original KEEPS trial. Additionally, they did not provide specific details about participants’ use of hormone therapy between the end of the original study and the start of the KEEPS study.

The approximately 10-year follow-up data was for a single assessment only, so additional long-term follow-up may be useful. It may also take longer to achieve true cognitive effects.

The researchers noted that there could be several reasons why no cognitive effects were observed. For example, the dose and duration of hormone therapy used in the initial research may not have been large enough to affect cognitive function.

Finally, the current article focuses on cognitive findings, but a future publication will cover data collected from brain scans.

Despite these limitations, the study highlights the potential safety of menopausal hormone therapy in the short term, which may increase its use in the future.

Rikki Baldwin, D.O.said an obstetrician-gynecologist at Memorial Hermann, not involved in this research. MNT:

“I hope this study will help clinicians and patients feel more comfortable using hormone therapy to treat menopausal symptoms.” There should be a detailed discussion regarding the timing, dosage, route and duration of treatment. But the use of hormone replacement therapy should be considered as first-line treatment in appropriate patients.

Doctors and other experts can advise on hormone replacement therapy for menopause and determine whether it is appropriate in individual situations. As the researchers note in this article, the timing of menopausal hormone therapy is likely a critical piece of the puzzle.

Baldwin said short-term hormone replacement therapy for menopause has potential benefits, including reducing or resolving hot flashes, insomniaAnd mood changes.

“It is not FDA approved, but has been shown to improve bone health,” Baldwin noted. “Anecdotally, hormone therapy was also said to improve cognitive health. The potential risks, as demonstrated by previous studies, are the worsening of cardiovascular diseases, thromboembolic eventsand treatment failure,” she added.

Ruiz noted the following regarding the benefits of short-term hormone replacement therapy for menopause:

“The short-term benefits are resolution of vasomotor symptoms and other symptoms such as insomnia and emotional lability. There may be improvements in libido. The urogenital tract functions better in the presence of estrogen, including the bladder and vaginal mucosa (…) Like any therapy, not everyone should use HRT due to medical contraindications to treatment. A woman should discuss HRT with her gynecologist to see if HRT is right for her.