Second Act: What Happens to the Ovary After Menopause?

For as long as most doctors can remember, the female ovary was set to expire one day. Indeed, once a woman went through menopause and her fertile years were over, the organ was considered finished—a spent shell that had done its job. In fact, one of the nation’s leading reproductive biologists, Francesca Duncan of Northwestern University, has stated that she used to think of the post-menopausal ovary as being about as useful as an appendix. Others clearly agree, with surgeons often removing the ovaries during other procedures on exactly that assumption—that nothing of value was being taken out. But it turns out we may have been wrong about the ovary. And the manner in which we found out we may be wrong says something uncomfortable about how little attention is paid to this part of the female body.

Five years ago, when Duncan and her team set out to study aging cells in human ovaries, they hit a snag. Ethically, researchers can’t take healthy ovaries from young women just to compare them across a lifetime. Because of that, the researchers could only work with ovaries removed for medical reasons from women between the ages of 50 and 75. Duncan has admitted that she was disappointed to be studying tissue that everyone assumed was inert. But when her team looked at those ovaries closely, they saw that the cells were making different proteins as the women aged. If the ovary had completely shut down as expected, it should have looked the same at 50 as it did at 75. But it didn’t. Duncan’s curiosity was sparked, and she realized something else was going on.

To get a clearer picture, the researchers examined mice, whose ovaries, like humans, also wind down when reproduction ends. Duncan and her team compared young mice, mice at the end of their reproductive years, and mice who had passed that point. Published this year, their findings are eye-opening. They discovered that the post-reproductive ovary had not switched off as previously thought. Instead, it had switched jobs. As expected, the follicles that hold eggs and produce hormones faded away once the body stopped being able to reproduce. But surprisingly, the ovary did not become an empty shell. It filled up with immune cells instead, including T cells, infection-fighting scavengers called microphages, and unusually large cells that do not belong in a resting organ. Likewise, the genes running the ovary tissue shifted as well. Instead of making life, it focused on the immune system. Eureka! The ovary stopped being a reproductive organ and started resembling an immune one. The organ once believed to be an empty husk after menopause was quietly reinventing itself.

It is too soon to proclaim that Duncan’s discovery is an entirely positive one, because research is not yet finished. The dramatic transformation of the ovaries was seen in mice, not women, and, of course, mice do not go through menopause the exact same way as women do. Thus far, human work is much narrower than the mice studies, but still important, showing that the post-menopausal ovary keeps changing with age. This means it is not the dead weight that has long been assumed. Whether a woman’s ovary undergoes the same immune shift as the mouse ovary is an open question that researchers are careful not to answer, yet.

Unfortunately, these changes may not be a definitive gift to support the immune system after menopause. Study researchers noted that the aged ovary appears to pump out low-grade, body-wide inflammatory signals that scientists increasingly link to diseases that become present with age. Duncan raised the unsettling idea that this notion could help solve the long-standing puzzle of why women tend to live longer than men yet spend more years in poorer health. If the post-reproductive ovary is quietly seeding inflammation throughout the body, it would be doing the opposite of nothing. It would be shaping how we age.

Thus far, the answers are unknown, and that alone proves that we don’t know all there is to know about the ovary. It is an organ present in roughly half of the human population; without it, we wouldn’t exist, and we are only now discovering that it may remain active for decades after women continue to live after menopause. According to Duncan, the size of that knowledge gap is “a little bit frightening.” She shared that we owe it to women’s health to finally study this stretch of life. Indeed, the human body keeps refusing to be as simple as many insist it is. For decades, modern medicine confidently declared the ovary was useless after menopause and cut it out. An organ we assumed became null and void is instead remaking itself in ways we don’t fully understand. Meanwhile, we understood less than we claimed, especially about women, as the body does extraordinary things we never knew. The real lesson here, despite knowing future study results, is that we must realize the importance of taking lifelong care of our bodies.