Menopause Found to Not Worsen HAE Severity in Most Women

A majority of women with hereditary angioedema (HAE) remain stable or even experience a reduction in disease severity after menopause, a small study reports.

Improvements were mostly observed in women whose HAE was sensitive to estrogen fluctuations before the time marking the end of their menstrual cycles. Only about 15% of menopausal women with HAE reported worsened symptoms, the study found.

Although small, the study provides insights into how HAE symptoms change after menopause, according to the investigators.

“A prospective study conducted during the transition to menopause period would be an interesting next step to better understand the changes brought about by menopause,” the researchers wrote.

The study, “Hereditary Angioedema with and Without C1-Inhibitor Deficiency in Postmenopausal Women,” was published in the Journal of Clinical Immunology.

HAE is a genetic disease that is mostly caused by mutations leading to a deficient anti-inflammatory protein C1-Inhibitor (C1-INH). However, it also can result from mutations in genes that do not affect C1-INH.

The disorder, characterized by sudden but temporary swelling in the deeper layers of the skin, also may be triggered by allergic reactions, illness, medications, stress, or hormonal fluctuations brought on by menstruation, pregnancy, and menopause. However, little is understood about how menopause itself impacts HAE with or without C1-INH deficiency.

Menopause is signaled by 12 months since a woman’s last menstruation.

To address that knowledge gap, researchers at multiple hospitals in France investigated how HAE activity had changed over time in 65 postmenopausal women, using retrospective data collected between June 2016 and June 2017.

The women had a median age of 62 at the time of the analysis, and had been through menopause at age 50.2, on average. The majority of patients (87.7%) had HAE with C1-INH deficiency, and most of these (49.2%) were classified as having moderate HAE. In contrast, 62.5% of patients with normal C1-INH were deemed asymptomatic. 

Overall, 70.7% of patients had estrogen sensitivity, meaning they experienced either HAE onset or worsening after estrogen fluctuations related to puberty, contraception use, menstruation, and pregnancy.

Regarding menopause, about half of the patients (50.7%) had severe menopausal symptoms, including hot flashes, joint pain, fatigue, sleep problems, and vaginal dryness. A total of 13 patients received hormone therapy for an average of 8.6 years; while all were estrogen-sensitive, only three experienced a worsening of attacks with such menopausal treatment.

“This study highlights that management of menopause in women with HAE is suboptimal and should encourage clinicians to improve the quality of life for these patients,” the research team wrote.

Following menopause, a majority of patients either experienced no change in HAE severity (46.1%) or a reduction in disease severity (38.5%); only 15.4% worsened. Of note, more women who were estrogen-sensitive before menopause experienced an improvement in HAE severity after menopause, although the differences were not significant.

Further research is required to better understand the effects of menopause on HAE, the researchers said.

Among the limitations of the study are its retrospective nature, relatively small size, lack of a primary comparison endpoint between patients, and the potential of memory bias when assessing the pre-menopausal stage.