“Gout is the most common type of inflammatory arthritis, yet it is a predominantly male disease,” explains Ritch te Kampe, PhD, MSc. “Despite an increasing prevalence of gout in the aging female population, most studies are performed on mostly male populations, and few examine the differences between sexes.”

For a paper published in The Journal of Rheumatology, Dr. te Kampe and colleagues aimed to improve insight into sex differences among patients with gout. “We sought to investigate and enhance existing data on the clinical differences between male and female patients,” he says. “We also wanted to explore the role of gout onset in women aged 55 and older to better understand the disappearance of the protective effect of estrogen.”

The study team collected data from 954 patients (83% male) newly diagnosed with gout who had been referred to two rheumatology clinics. Clinical differences and comorbidities of each sex were compared universally. Sex differences in comorbidities were further explored in multivariate logistic regression analyses adjusting for age, BMI, smoking, and alcohol consumption in both the total group and in those with gout onset at age 55 and older (as a surrogate for menopausal state).

Lifestyle Factors Contribute to Sex Differences in Gout

Dr. te Kampe and colleagues expected to confirm previously reported sex differences and hypothesized that the differences in clinical characteristics and comorbidities between sexes would be strongly reduced in those with a first gout flare at age 55 and older, and that no difference in uric acid (UA) excretion would be present between male and female patients with gout aged 55 and older. They found that:

  • Female patients with gout, when compared with male patients, are older and have more frequent obesity and cardio-renal comorbidities.
  • If gout presents at age 55 or older, sex differences in comorbidities are attenuated and disappear when accounting for lifestyle.
  • Lifestyle factors contribute to sex differences in gout, regardless of age of gout onset.

Female Patients Used Diuretics More Often Than Male Patients

“When compared with male patients, female patients with gout are prescribed diuretics more often, consume alcohol less frequently, have a higher serum UA level at presentation, and have more frequent comorbidities, such as hypertension, heart failure, type 2 diabetes, and advanced renal insufficiency,” Dr. te Kampe says (Table). “Women referred to gout clinics used diuretics more than three times more frequently than men. Starting diuretics has previously been associated with hyperuricemia, and thus, an increased risk for gout in women. Although diuretic use has been shown to be a safe and effective first-line treatment for hypertension, our population of females with gout was characterized by more frequent diuretic use compared with the male gout population, which was partly related to the higher prevalence of hypertension.”

Dr. te Kampe says the study is the first, to his knowledge, to provide a greater understanding of sex differences in patients with gout and highlights the need for awareness of the potential effect of sex-specific pathophysiology and management of gout. “Women are more often obese compared with men, both in our study population and in the general population,” he says. “Sex differences in obesity can partly be explained by the influence of chromosomal, hormonal, and neuroendocrine influences on energy balance and fat distribution. However, they can also be explained by gender-specific behavioral and sociocultural factors. Moreover, women may be treated more frequently with diuretics compared with men, partly based on biological grounds, but also on the behavioral choices of the prescribing physician.”

Dr. te Kampe and colleagues express the need for future research focused on understanding whether prevention and management of gout should be approached differently between sexes before and after the age of menopause. “In an era that encourages personalized healthcare, research into contextual factors becomes increasingly important, as it allows physicians to understand which subgroups of patients respond differently to available drugs or drug strategies,” says Dr. te Kampe. “Unraveling the influence of different contextual factors on effectiveness and safety of gout treatment could lead to more tailored strategies with better outcomes, less side effects, or both.”