Current discourse on women's health in nephrology largely focuses on reproductive health and pregnancy, overlooking other sexual functions impacted by chronic kidney disease (CKD). The majority of women with CKD are beyond the typical child-bearing age. This population is predisposed to gynecologic problems such as decreased libido, menstrual cycle abnormalities, and early menopause, which may be directly impacted by their kidney disease or its treatment. Some of these common women's health issues outside of reproduction were touched upon during the recent Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference on Women and Kidney Health (1). However, the main focus of this conference was on pregnancy and fertility, reflecting the lack of attention that matters outside this arena receive.
Women's health in CKD is a topic that is well outside of the comfort zone of many practicing nephrologists. In a 2019 survey of 154 nephrologists from the United States and Canada, only 55% reported having fellowship training in women's health. A significantly smaller percentage felt confident counseling on common women's health issues, like contraception, menstrual disorders, or menopause, compared with counseling on issues related to pregnancy (2). This is not surprising given the relatively sparse literature on this subject.
Many of the investigations into the prevalence and pathophysiology of sexual dysfunction and premature menopause in CKD were done in the 1970s through early 2000s. These investigations laid the groundwork for what we know today. In women with CKD and end stage kidney disease, there is disruption of the hypothalamic-pituitary-gonadotropin axis due to loss of pulsatile gonadotropin-releasing hormone (GnRH) (3, 4). This results in low follicle-stimulating hormone (FSH) and luteinizing hormone secretion by the pituitary and thus low estradiol production by the ovaries. The etiology of the loss of pulsatile GnRH is not fully understood, but excess prolactin, catecholamines, and endogenous opioids may contribute (3, 5, 6).
The consequences of this hormonal dysregulation are widespread. In a survey of 659 women with CKD, 84% reported sexual dysfunction, based on the female sexual function index score, and only 35% reported being sexually active (7). This significantly impacts the quality of life of patients with CKD. While similar findings in the male population have spurred research on interventions for erectile dysfunction in CKD, sexual dysfunction in women with CKD remains an under-investigated area in nephrology. Another survey showed that women with CKD tended to experience menopause, on average, 4.5 years before those without CKD, putting them at increased risk of cardiovascular disease and osteoporosis (8–10). In a cross-sectional study that made national news in 2023, Faubion et al. (11) estimated that missed work days due to menopause symptoms in the general population cost the United States a whopping $1.8 billion yearly.
Barriers to research of sexual dysfunction in CKD are many: varying definitions of sexual dysfunction, stigma, and multifactorial etiologies, to name a few (12). Premature menopause, although still multifactorial, is a relatively easier target. However, laboratory diagnosis of menopause is difficult in advanced CKD due to amenorrhea in the setting of low FSH levels, as opposed to the high FSH characteristic of menopause (13). As a result, many studies on menopause in CKD rely on self-reported questionnaires of menopausal symptoms. In spite of these obstacles, several treatment options have been explored. Restoration of menstruation was noted in amenorrheic premenopausal women with kidney failure after successful kidney transplantation, hormone replacement, or bromocriptine use (14–16). The lack of adequately powered randomized clinical trials on the safety of hormone replacement or prolactin-lowering medications in CKD means that there are no guidelines for their use. The Kidney Disease Outcomes Quality Initiative (KDOQI) Clinical Practice Guidelines for Cardiovascular Disease in Dialysis Patients from 2005 suggested that guidelines from the North American Menopause Society may be followed (17). However, these have changed since 2005 due to more data about cancer risk in the general population on long-term hormone-replacement therapy, and KDOQI recommendations have not been readdressed since.
The remarkable paucity of research and lack of funding in nephrology for women's health outside of reproduction are glaringly apparent (18). Time and time again, reports and reviews have shown the burden of sexual dysfunction and premature menopause on women with CKD, highlighted the gaps in data, and demonstrated the need for a trans-disciplinary approach to investigation. In recognition of this, the National institutes of Health started the Office of Research on Women's Health in 1990 and continues to mandate that investigators include sex as a variable in basic research and female trial participants in grant submissions (19). However, we as a nephrology community must pursue additional efforts to close these gaps of knowledge. Academic centers may be able to help shine the spotlight on this topic by providing more fellowship training on women's health outside reproduction. This could spur more participation in interdisciplinary conversations to better align patient priorities with research directions.
References
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Kidney Disease: Improving Global Outcomes (KDIGO). Controversies Conference on Women and Kidney Health. February 2–5, 2023. https://kdigo.org/wp-content/uploads/2022/06/KDIGO-Women-and-Kidney-Health-Conference_Scope-for-Public-Review.pdf#:~:text=This%20KDIGO%20Controversies%20Conference%20will%20convene%20a%20global,developed%20hypertensive%20disorders%20of%20pregnancy%20or%20pregnancy-related%20AKI
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Kramer HM, et al.; HELP Study Group. Hemodialysis and Estrogen Levels in Postmenopausal (HELP) patients: The multicenter HELP study. Am J Kidney Dis 2003; 41:1240–1246. doi: 10.1016/s0272-6386(03)00357-3
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Lim VS, et al. Hyperprolactinemia and impaired pituitary response to suppression and stimulation in chronic renal failure: Reversal after transplantation. J Clin Endocrinol Metab 1979; 48:101–107. doi: 10.1210/jcem-48-1-101
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National Kidney Foundation. NKF KDOQI Guidelines. 2005; http://kidneyfoundation.cachefly.net/professionals/KDOQI/guidelines_cvd/menopause.htm
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Bird CE. Underfunding of research in women's health issues is the biggest missed opportunity in health care. The Rand Blog. Rand Corp. February 11, 2022. https://www.rand.org/blog/2022/02/underfunding-of-research-in-womens-health-issues-is.html
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National Institutes of Health. Amendment: NIH Policy and Guidelines on the Inclusion of Women and Minorities as Subjects in Clinical Research. November 28, 2017. https://grants.nih.gov/grants/guide/notice-files/NOT-OD-18-014.html
