Menopause marks a period of significant hormonal changes for women that can impact a range of organs and body systems, including the musculoskeletal system, and it can significantly impact quality of life. “Previous studies suggest there is a clinical relationship between hormonal status and rheumatoid arthritis (RA) disease activity among women,” explains Kaleb Michaud, PhD. “For example, RA symptoms often improve or subside during pregnancy.” This may be due to estrogen levels increasing during pregnancy. Conversely, estrogen levels typically drop around the time of menopause. When this occurs, RA symptoms may worsen.

Some women first experience RA symptoms around the time they start menopause. Other research has shown that early menopause is associated with a greater risk of developing RA when compared with normal or late menopause.

 

Taking a Closer Look

For a study published in Rheumatology, Dr. Michaud teamed up with lead author Elizabeth Mollard, PhD, APRN-NP, and others to investigate the association of menopause with functional status outcomes in women with RA. They used data from the National Data Bank for Rheumatic Diseases (now referred to as FORWARD), one of the largest patient-reported databanks in the United States. Participants completed a survey upon entering the study and follow-up questionnaires every 6 months. These surveys included the Health Assessment Questionnaire (HAQ), which measures pain and disability while performing normal activities and other important parameters, like drug-related adverse effects. Positive scores on the HAQ indicated worsening functional status and greater functional decline; negative scores reflected better functional status and less functional decline.

To be eligible for the study, women needed to receive an RA diagnosis before menopause and to have completed at least 2 HAQs between 2003 and 2017. More than 8,000 patients met the inclusion criteria. Univariate and multivariable analyses were performed to account for potential confounding variables.

Findings from the study revealed that women who were pre-menopausal had less functional decline than women who were post-menopausal. The ever-use of hormonal replacement therapy, ever having a pregnancy, and longer length of reproductive life were associated with less functional decline. “Our results were robust and strong, even after we adjusted for other significant factors, including age,” says Dr. Michaud.

After menopause, the trajectory of functional decline worsened and accelerated in women with RA, according to Dr. Michaud (Figure). “Functional decline was also worse for women who became menopausal at an earlier age,” he says. “Overall, our data indicate that menopause has a significant impact on the level and rate of functional decline in women with RA.”

 

Examining Implications

Clinical guidelines recommend that healthcare providers make efforts to counteract the increased health risks that come with menopause. “When women become menopausal, it’s an important time for clinicians to educate women on the importance of optimizing their health,” Dr. Michaud says. “Clinicians should consider being more aggressive treating and controlling RA symptoms.” Close collaboration with patients is necessary to finding the most appropriate treatments at all stages of RA to prevent joint damage and other related health problems while maintaining optimal physical functioning.

Dr. Michaud notes that more research is needed on the relationship between functional decline and hormonal changes. “Collectively, menopausal women are an understudied group of patients,” he says. Data are needed on RA symptoms and functional status throughout the menstrual cycle and other hormonal life events to improve clinicians’ understanding of the involvement of hormones in RA disease status and functional decline.

References

Mollard E, Pedro S, Chakravarty E, Clowse M, Schumacher R, Michaud K. The impact of menopause on functional status in women with rheumatoid arthritis. Rheumatology (Oxford). 2018 Jan 29 [Epub ahead of print]. Available at: https://academic.oup.com/rheumatology/advance-article-abstract/doi/10.1093/rheumatology/kex526/4810410?redirectedFrom=fulltext.

Harlow SD, Karvonen-Gutierrez C, Elliott MR. It is not just menopause: symptom clustering in the Study of Women’s Health Across the Nation. Womens Midlife Health. 2017 Jul 27 [Epub ahead of print].

Bengtsson C, Malspeis S, Orellana C, Sparks JA, Costenbader KH, Karlson EW. Association between menopausal factors and the risk of seronegative and seropositive rheumatoid arthritis: results from the Nurses’ Health Studies. Arthritis Care Res (Hoboken). 2017;69:1676-1684.