The Roles of Sex and Gender in Psoriatic Arthritis

By Jill Tyrer | Dec. 17, 2024

If more physicians and patients recognized how women and men experience psoriatic arthritis (PsA) differently, then women might get earlier diagnosis and treatments, and ultimately better outcomes, according to Laura Coates, MD, PhD, of the University of Oxford. She discussed sex-related differences in PsA and their implications at November’s American College of Rheumatology annual scientific conference, Convergence.

Women typically are aware of PsA symptoms and start seeking help from their primary care doctors two to three years before they actually receive a diagnosis. Despite that, getting a correct diagnosis can take several years after symptom onset for both men and women, she says. Women may get X-rays in response to their complaints, but PsA evidence doesn’t show up on early X-rays and doctors may not know what to look for, even though psoriasis usually precedes joint symptoms.

There are other sex-related symptom differences in PsA:

• In women, PsA typically involves five or more joints (polyarticular), where men usually have four or fewer joints (oligoarthritis) affected.
• The spine is usually involved in men, but not in women.
• Women tend to have more tender joints and more swollen joints than men.
• Men typically have more skin involvement — psoriasis
• Enthesitis (inflammation where tendons and ligaments attach to bones) affects women more
• Dactylitis (swollen, sausage-like fingers and toes) and higher levels of inflammation markers in the blood appear more in men
• Both sexes are just as likely to have finger- or toenail involvement, with pitting and crumbling.

These differences are present in early disease and they persist as the disease progresses, Dr. Coates adds.

PsA Impacts and Treatment Goals

Clinical trials have not historically looked at sex-related differences, Dr. Coates says, but she and her colleagues were able to determine that when it comes to factors that are important to those living with PsA, women are typically much more impacted.

According to patient-reported outcomes, “Women report higher impacts in pain, fatigue, anxiety and quality of life. [Health Assessment Questionnaire reports are] consistently worse across studies,” she says. The impact on sleep is “much, much higher” for women, and anxiety and depression are also greater in women than in men.

Still, when patients were asked, “Do you think your disease is reasonably controlled?” women had higher disease-impact scores, but they also were happier, Dr. Coates says.

The point is that women and men with PsA should be treated with a strategy called “treat-to-target,” in which the patient and physician work together to achieve a level of disease control that enables the patient to live well with it and achieve their treatment goals, even if they are not in complete remission.

The sex-related differences might not affect the medication or treatment choice, Dr. Coates says, but they may affect how she approaches treat-to-target. For a man, the treatment goal might look very different because they experience the disease and perceive remission and treatment goals differently.

Furthermore, because women start talking to their doctors about symptoms several years before diagnosis, rheumatologists are “missing a massive opportunity” to catch their disease early, Dr. Coates says. “Men are not presenting early and that’s also a problem because they’re probably having [damage from the disease], but they not seeking treatment.” That shows a need to educate both patients and doctors, she adds.

Still, she says, “What we know is pretty limited. We can see patterns of disease, but we have no idea what’s driving it. We haven’t studied it.  We don’t understand how hormones influence the immune system.”

But there does seem to be a connection. She described one patient whose mild disease got much worse with menopause. Rather than try a stronger PsA medication, she tried hormone replacement therapy, and her symptoms receded.

“There’s much more [research] to do around menstrual cycle, pregnancy and menopause,” Dr. Coates says.

Treatment Responses and Pain

Sex-related differences also apply to how men and women respond to treatments and pain, says Lihi Eder, MD, PhD, of the University of Toronto.

“A one-size-fits-all approach [to treatment] may not be appropriate,” she says. For example, sex differences have been found to be such a significant factor in cardiology that treatment guidelines have been revised and many medications are now known to pose a greater risk to women. Much more research into these differences is needed in rheumatology, Dr. Eder says. “We need to better understand why these differences happen. We assume that what works for males works for females and that might not be true.”

Gender Differences

We know there are biological differences in how each sex experiences pain, in hormones and in the immune system. But there are also differences in gender: how being a man or women in a given society could influence a person’s behavior — how they interact with their physician, how they access care, their coping mechanisms, their adherence to medications and more.

Women who quit taking their medication say it’s because their joint symptoms aren’t improving or they are having a hard time with side effects. When men don’t take them, it’s just usually because they are worried about potential side effects or they just don’t like taking drugs.

“These are different in men and women and certainly could influence their treatment response and other aspects,” Dr. Eder says.

Men and women also experience pain differently. In general (not just in PsA), women have higher pain scores and a lower threshold for pain. They also have different patterns of pain, including more diffuse pain, like centralized pain or possibly inflammatory pain.

The differences are partly based in social norms and expectations, but they also appear to be biological. In mice studies, pain in male mice depends on immune cells in the spinal cord. In female mice, T cells seem to control pain, Dr. Eder says.

PsA clinical trial results show that men are more likely to have a positive treatment response than women to biologic medications, and JAK inhibitors like tofacitinib (Xeljanz) are the only psoriasis drugs to which men and women seem to have similar responses. JAK inhibitors are not considered first-line or even second-line medication for PsA, and Dr. Eder suggests that methotrexate might make more sense for women, although there is little evidence to support that so far.