Ask An Expert: Lupus and Women’s Health with Penelope Howards

By Shelby Crosier

In the United States, an estimated 1.5 million people are living with lupus, a chronic autoimmune disease that causes pain, inflammation, and damage to organs. About 90% of cases are in women, who are most commonly diagnosed between the ages of 15 and 44. Despite its prevalence, lupus has historically been under-studied and difficult to diagnose, leaving gaps in scientific understanding. Penelope Howards, PhD, associate professor of epidemiology, is helping to fill those gaps.

A reproductive epidemiologist by trade, Howards has long focused on pregnancy and reproductive health in people with chronic conditions, including lupus, sickle cell disease, and cancer. Here, she discusses her work with lupus, its complicated effects on fertility and women’s health, and what we still don’t know.

Tell me about your research on lupus.

When I was doing my work with cancer survivors, I realized that one of the very toxic chemotherapy agents was also used to treat people with lupus, but there wasn’t as much attention on them. So that's how I started getting interested in studying people with lupus.

I've collaborated a lot with Sam Lim, a rheumatologist who oversees the Georgia Lupus Registry and GOAL, which is the Georgians Organized Against Lupus study. We secured funding to study fertility in women with lupus, including measuring anti-Müllerian hormone (AMH), which is a marker of ovarian reserve, or how many eggs someone has left, which decreases with age. During the study, we interviewed women and asked them about their experiences of infertility, and we also measured AMH in their blood.

How does lupus affect fertility?

One big thing that can affect fertility in people with lupus is their treatments. In our study, we looked at women who were using cyclophosphamide. When we controlled for age, we found that women with lupus who used cyclophosphamide had lower AMH levels. They were about three times as likely to have an AMH level that was below 1.0 nanograms per milliliter, which is extremely low. The women who used cyclophosphamide, even when they were young, had AMH levels that were about equivalent to people who had not used that treatment and were in their forties. It’s also important to note that people who are taking cyclophosphamide have more lupus complications, which may also affect their reproductive health.

What other effects can lupus have on women’s health?

One important thing to know about lupus is that it can affect multiple organs, including both the kidneys and the heart. Because of that, women with lupus are more likely to have cardiovascular events prior to menopause than people without lupus. Although women with well-controlled lupus can have healthy pregnancies, women with lupus are at greater risk of complications during pregnancy, such as preeclampsia and other hypertensive disorders. It can also influence birth outcomes; women with lupus are more likely to have cesarean sections and have a higher risk of preterm birth.

We don't want the message to be that women with lupus shouldn't get pregnant. It’s more about making sure that there's clear communication about the benefits of timing pregnancy to periods of low lupus activity, providing support for women, and monitoring them in order to identify potential complications early rather than trying to give some kind of message that they shouldn't become pregnant.

What groups of people are most at risk for lupus, and why?

Lupus disproportionately affects people who are assigned female at birth—it’s about eight or nine to one in terms of affecting people assigned female at birth versus assigned male at birth. On top of that, African Americans or people with African ancestry are three times more likely to have lupus than people who are white, and they are more likely to have more severe manifestations of lupus.

As to why these groups are more at risk—I don't think it's entirely clear. It’s not even completely clear what causes lupus, and because of that, it's hard to figure out why it differs across populations. However, there are a lot of inequities that contribute to other adverse health outcomes that may also be affecting lupus.

What do you think everyone should know about lupus and fertility?

I feel that it's time to make sure that people are getting what they need. For cancer survivors, one of the options they have is to use fertility preservation before treatment. That’s where they extract the eggs before they're damaged by their cancer treatment and either freeze the eggs or fertilize the eggs and freeze the embryos. Then in the future, cancer survivors can try IVF if they're not able to get pregnant without it. With cancer, you do fertility preservation before cancer treatment. The problem is that for lupus the best timing is not clear. Also, because fertility preservation affects hormone levels, it could potentially cause a lupus flare, which would not be ideal. But then on top of that, in most states, including Georgia, fertility preservation is not currently covered by insurance, so you have to have some financial resources to proceed with that. This is especially important because lupus disproportionately affects African American people, who already have fewer resources on average.

The good news in our study was that even though women with lupus were more likely to report experiencing a period of infertility than women without lupus, this did not appear to prevent them from meeting their reproductive goals even without using fertility preservation.