Heart disease tends to hog the spotlight for sex differences in health — it’s the number one killer of men and women, but it affects an especially high number of women and people of color. And advocacy efforts such as the American Heart Association’s Go Red For Women campaign has brought well-deserved attention to these underrepresented groups. According to a new study published Journal of the American Society of Nephrology, though, demographic differences sometimes work in women’s favor. In this case, the female sex hormone estrogen may protect the kidneys.

Prior animal studies have shown female mice and rats are less likely to experience renal, or kidney, damage compared to males, lead study author Dr. Judith Lechner, of the Medical University of Innsbruck in Austria, told Medical Daily. She added that when researchers surgically removed their ovaries, the females lost this advantage. The key seems to be estrogen, the hormone that, while present in men, is not as pronounced as it is in women.

“Since such literature reports argued for a role of female sex hormones in kidney disease, we thought that actions of the hormones on normal renal tissue might provide protective effects, making kidneys less susceptible to damage,” Lechner said.

To put this theory to the test, Lechner and her colleagues examined whether hormonal changes due to a woman’s menstrual cycle might affect the health of kidney cells. They recruited 11 healthy, unmedicated, and naturally ovulating women aged 25 to 44. They also enrolled six postmenopausal women aged 57 to 64 and eight men aged 24 to 73 to act as controls.

Participants submitted daily urine samples so that study authors could measure for enzymes that are excreted when kidney cells are damaged. And the results showed increases in these enzymes during ovulation and menstruation; levels were lower in postmenopausal women and in men.

"This result suggests that cyclical changes of female hormones might affect renal cell homeostasis, potentially providing women with an increased resistance against kidney damages,” Lechner said. Homeostasis helps regulate temperature and balance acidity and alkalinity levels. “Thus, recurring changes of sex hormone levels, as brought about by the natural menstrual cycle, might be involved in periodic tissue remodeling not only in reproductive organs, but to a certain extent in the kidneys as well,” she added.

Lechner hypothesizes that estrogen might help to replace damaged cells. During cycle phases of high estrogen exposure, kidney cells might be induced to grow, she explained, “while at time points of decreasing estrogen levels damaged or simply older cells might be discarded into the urine.”

That said, the study is not saying that estrogen is the sole reason fewer women develop kidney disease and failure. Their enzyme levels match men’s once they go through menopause, which definitely argues for the importance of the female hormones — but this could also be a matter of age.

“Certainly the ovulating women are younger than the post-menopausal women,” Dr. Marie Csete, president and chief scientist of Huntington Medical Research Institutes in California, told Medical Daily, “but is this just an estrogen effect or are other more complex factors of aging promoting the changes they found?” Csete was not involved with Lechner’s study.

What Lechner can say for sure is that her team found the connection thanks to an unusual study design. Typically, experimenters looking at female sex hormone effects compare single samples from menstrual phases of high and low hormone exposure, she said, like the luteal phase after ovulation and the early follicular phase when ovaries get ready to release an egg. Instead, Lechner relied on daily samples over multiple menstrual cycles.

“That meant a lot of work, but we were very enthusiastic about the results,” Lechner said.

Overall, the study authors simply wanted to learn more about the underlying mechanisms of women’s resistance to kidney failure. There are lingering questions, such as the influence of age, that they plan to investigate further. But for now, they believe their findings provide important clues for improved patient care in the future.

Lechner concluded: “In this respect, we hope that our research will contribute to develop new strategies for the benefit of men and women alike.”

Source: Seppi T, Lechner J, et al. Sex Differences in Renal Proximal Tubular Cell Homeostasis. Journal of the American Society of Nephrology . 2016.