Stroke in Women: The Roles of Depression and Hormone Exposure

Author: Leah Lawrence

MedCentral

It is well known that stroke kills more women than it does men, but associations between depression and stroke, as well as hormone exposure and stroke, are still emerging for this patient population. These links were addressed in detail at a pre-conference session of the American Heart Association/American Stroke Association’s 2024 International Stroke Conference (ISC).

Post-Stroke Depression Risk in Women

Women are between 20% and 70% more likely to experience post-stroke depression than men, according to M. Patrice Lindsay, RN, PhD, FWSO, lead for Engagement and Stroke Strategies with the Heart and Stroke Foundation of Canada. Although it is somewhat well known that women have worse outcomes and health-related quality of life after stroke, more attention needs to be paid to the fact that depression appears to be a contributing factor, she told the ISC audience.

There is more and more evidence showing that women have a high risk for post-stroke depression, Dr. Lindsay noted. She cited one study that showed that post-stroke depression was reported in about 30% of men compared with closer to 40% of women. A study of sex differences in post-stroke depression in the elderly showed that at 1.5 years post-stroke, women were 20% more likely to develop post-stroke depression than men.

Several predictors of post-stroke depression have been identified, including being female, a prior history of mental health issues, younger age at stroke onset, stroke severity, lower education status, and a lack of social support.

“Despite this, it is not being well-treated or well-recognized,” Dr. Lindsay said.

To illustrate her point, Dr. Lindsay asked the audience how many automatically refer a stroke patient for a mental health evaluation. When only a minority of hands were raised, she emphasized that this referral should be a regular part of stroke recovery.

Physicians can open these conversations by asking women who have experienced stroke about their mental health status. Questions can be as simple as asking what a day in their routine life looked like before the stroke and what it looks like now. Providers can look for physical signs of depression and evaluate sleeping and eating patterns. Ask about the patient’s hopes and fears, and don’t shy away from addressing issues related to sexuality and intimacy, which often can contribute to mood changes, suggested Dr. Lindsay.

She further explained that since mental health conditions are the result of a complex interaction of psychological, biological, and social factors, multimodal interventions should be considered. This means pharmacological and nonpharmacological options.

“Tailor recommendations and assistance to fit a woman’s means, not to leave them out if they lack financial means or time due to responsibilities,” Dr. Lindsay advised, adding that mental health and education about resources and coping strategies should be addressed not only with the patient but also with their families and caregivers.

Finally, Dr. Lindsay acknowledged the difficulty of accessing mental health resources in many areas, citing that in Canada the waitlist to see a community-based psychologist that patients pay is between 6 to 12 months. She encouraged providers to advocate for better access to stroke rehabilitation and recovery, including more mental health services in communities.

Mary Ann Bauman, MD, agreed that access to mental health care is not always easy. “The recommendation for an automatic referral for mental health evaluation is an excellent idea, but in practice, is often limited by insurance coverage, cost, or patient resistance,” she said. Dr. Bauman is the current American Heart Association president for the Western States region board of directors and a primary care physician.

However, primary care providers are in a unique position to identify depression after stroke because the trust relationship has already been established, Dr. Bauman said.

“We usually see patients more frequently than specialists, and so they are more likely to open up when asked about depression symptoms,” she said.

Hormone Exposure and Stroke Risk in Women

Malveeka Sharma, MD, MPH, discussed the rising evidence for hormone exposure and stroke risk in women. Dr. Sharma is an assistant professor of neurology at the University of Washington, Seattle.

Exposure to endogenous hormones, both progesterone and estrogen, occur naturally at different levels in different individuals and fluctuate within a female’s menstrual cycle and throughout their lives (eg, during pregnancy and perimenopause), she noted. Interestingly, she cited a recent observational study found that women with higher exposure to endogenous hormones – either because of pregnancies or longer period from menarche to menopause – had a smaller burden of white matter disease, indicating some protection for the brain with age.

According to Dr. Sharma, women also have varying exposure to exogenous hormones throughout their lifetime. In the United States, for example, it is estimated that almost 65% of women aged 15 to 49 years are currently using a method of contraception. In Europe, about one-third of perimenopausal women and 13% of postmenopausal women are taking hormone replacement therapy (HRT). These exogenous hormones are typically in either progestin or combined progestin/estrogen preparations.

“Exogenous estrogen in formulations for oral contraception or in HRT does impart increased risk for stroke, but there is a lot of information that we do not understand,” Dr. Sharma said, “such as if there are alternative routes of administration that would be better or if lower doses of estrogen might impart benefit without increasing stroke risk.”

Despite there being more than 100 million women worldwide needing hormonal treatments, there are “limited studies to help guide decision making on risk of starting oral contraceptives and HRT in patients who have had strokes,” she noted.

In terms of clinical implications, that means that for any patient with high risk factors for stroke, such as tobacco use or vascular risk factors, oral contraceptives or HRT with estrogen should probably be avoided, Dr. Sharma said. Additionally, future hormonal treatments should be avoided in those patients who have experienced stroke, if possible.

“With such a large percentage of women relying on hormonal methods of contraception, it is imperative that we determine the best route of delivery/dose to minimize and/or eliminate stroke risk,” Dr. Bauman said. “There are still too many unknowns.”