Even when it comes to osteoarthritis, men and women differ. And those gender differences matter because better, more timely treatments may come with understanding how men and women develop OA and why.

“Men and women may need interventions that are different. And earlier recognition of issues may be needed more for one gender than another,”  says Barbara A. Rakel, PhD, associate professor in the College of Nursing at the University of Iowa in Iowa City.

In Rakel’s 2011 study of men and women with knee osteoarthritis, for example, women had more pain than men but took similar amounts of medication. “Although we treat men and women similarly,” says Rakel, “that women have more pain should probably drive treatment that’s different than for men.”

Still, gender differences are not easy to tease apart, nor are they entirely understood. Below, researchers describe what they know.

Women Get the Lion’s Share

According to the Centers for Disease Control and Prevention, men have a 45 percent lower risk of knee OA and a 36 percent lower risk of hip OA than women.

“Women have the higher burden of disease,” agrees Mary I. O’Connor, MD, chair of the Department of Orthopaedic Surgery at the Mayo Clinic in Jacksonville, Fla. “We [women] are much more likely to get knee osteoarthritis, for example, particularly after menopause when our risk goes way up.” 

According to a 2010 study review at the University of California, that’s true of hip and hand OA as well. 

Estrogen’s Role

Although cartilage contains estrogen receptors (molecules that respond to estrogen), no data definitively links increased osteoarthritis in women to hormones, says Dr. O’Connor.  Still, some studies have found a possible association including a 2006 University of Michigan study, which found that women with knee OA are likely to have low levels of estrogen.

Studies looking at the effect of hormone replacement (HRT) are equivocal. For instance, a 2006 study at the University of Iowa that examined data involving 26,000 women from the Women’s Health Initiative found that women taking estrogen had significantly lower rates of hip replacement but not knee replacement.

“Women on hormone replacement therapy might be less likely to lose cartilage over time”— as evidenced on x-rays — “and less likely to get hip OA or hip replacements,” says rheumatologist/epidemiologist  and review author Joanne M. Jordan, MD, MPH, director of the Thurston Arthritis Research Center at the University of North Carolina in Chapel Hill. “Yet in another study that looked at HRT for preventing knee pain” — a 1996 multi-institutional study including the University of California-San Francisco and others  — “it didn’t appear effective.”
 

The Gender Within Our Bones

Structure may explain some gender differences, too. A 2007 study at the University of Rhode Island examining 97 healthy men and women found that bone, cartilage thickness and volume were all greater in men than in women. 

“Women lose knee cartilage faster than men,” says Rakel.  Women lose cartilage from their tibia (the larger bone between the knee and ankle) at four times the rate of men, and they lose cartilage from the kneecap at three times the rate, according to a 2009 study at Monash University in Melbourne, Australia.

A 2007 study of sex and age on the change in cartilage volume in adults at the Menzier Research Institute in Hobart, Australia, found that greater cartilage loss in women than in men began at age 40 and increased with age. 

Conversely, a 2009 Osteoarthritis Initiative Study in the Annals of Rheumatic Diseases found that men had a slightly greater rate of cartilage loss.  But that study measured loss only over one year and in only one knee.

Fat’s Gender Signature

Obesity may also play a part in OA’s gender differences. “In our study, we found that women with knee osteoarthritis have an average body mass index (BMI) of  35 and men of 33, a significant difference,” says Rakel. A BMI — a measure of fat in relation to height — above 30 is considered obese.

A 2011 University of Michigan study of 1,066 participants found that obese women with high levels of leptin, a pro-inflammatory hormone involved in regulating appetite and fat storage, were more likely to have knee osteoarthritis than those with lower levels; the opposite was true for men.

Meanwhile, men, obese or not, who had higher levels of insulin resistance were more likely to have OA than men without.  Almost the opposite was true for women.

The difference may be a reflection of body composition, brain responsiveness, or [the effect of] different sex hormones, says epidemiologist Carrie Karvonen-Guiterrez, PhD, an assistant research scientist at the University of Michigan School of Public Health in Ann Arbor: “But both high leptin levels and insulin resistance [suggest] metabolic dysfunction.”
 

Insulin resistance is associated with belly fat, something men are more likely to tote. Leptin levels are related to what’s called subcutaneous fat — the fat that lies just under the skin, which women are more likely than men to have.

Researchers are also looking at whether joint shapes may make a difference in why women get more OA, says Jordan.  Women, for instance, have narrower thigh bones than men, and their bones are placed differently so that some researchers believe that women may experience more joint pressure. “But this has not been verified,” says Jordan.

Severity and Pain

Rakel’s 2011 study of 208 men and women with knee osteoarthritis found that women with knee OA had significantly more pain as they moved, and they couldn’t move as well as men.  At rest, their pain was similar.  “But when we [measured activity], women were moving around as much as men,” says Rakel.  Although researchers can’t explain why, Rakel speculates that women may just need to get around more.

Surprisingly, despite greater pain and disability, x-rays showed that women had less severe OA than men.  Men’s stronger muscles may explain why getting around is both easier and less painful for them than women, despite worse disease, says Rakel.  According to a 2004 study at the University of Pittsburgh, quadriceps (thigh muscle) strength makes function easier in those with knee OA.

Surprisingly, women with OA are far less likely to have knee replacements than men.  “In focus groups, women appear to have more concerns about recovery, are less willing to endure the pain of recovery, and hesitate to disrupt a caregiving role, “ says Kelli Allen, PhD, associate research professor at Duke Medical Center in Durham, N.C.

But gender bias may also play a role. A 2008 study at the Hospital for Sick Children in Toronto found that  physicians were 22 times more likely to recommend knee replacement to men than to women. “So maybe part of the reason women wait long is because they’re not encouraged or told that they should have surgery earlier because of an unconscious bias by the provider,” says O’Connor.

The difficulty is that when women wait, they go into surgery with more pain and dysfunction than men do, says O’Connor. “So, they never catch up with the men’s improvement, even those that get the same [degree] of benefit from surgery that men do.” 

The Difference From Childhood

Researchers are just beginning to examine if cartilage differences between men and women exist from childhood on. In a 2001 Tasmanian study of 92 children, 9 to 18 years old, the boys already had 16 to 31 percent more cartilage than the girls.

“Not all studies agree,” notes Jordan. “Still the potential is very exciting.  If we can see differences in boys and girl, then those may be a target for prevention.”