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Could Arthritis Enhance Male Fertility?

— Link seen in epidemiological study, but reasons remain a mystery

MedpageToday
A photo of a parents and their two boys and little girl holding Norwegian flags in front of a house.

Infertility does not seem to be a problem for men with inflammatory joint diseases, a large Scandinavian study indicated.

In fact, men with arthritis showed lower rates of childlessness relative to a control group, and had fathered more children on average, according to Gudrun David Sigmo, of Stavanger University Hospital in Norway, and colleagues.

National registry records for 10,865 Norwegian men with inflammatory arthritis indicated that 21% had fathered no children, compared with 27% (P<0.001) of a 54,325-person control group matched by age and county of residence, the researchers .

Overall average numbers of children per man were 1.80 among cases versus 1.69 for controls (P<0.001).

Of course, these registry data don't shed much light on reasons why arthritic men would be more fecund, nor have previous studies. At least two groups found no difference in sperm quality, and sex hormone secretion did not seem to be affected by an inflammatory arthritis diagnosis. Common medications such as methotrexate and tumor necrosis factor inhibitors might be a factor, but Sigmo's group found little hard evidence to support it. (Whether men with arthritis might stay home more than others, and thus have more opportunities for sex, did not come up in the researchers' discussion. The data didn't include factors such as employment status or physical activity levels.)

Sigmo and colleagues undertook the study after noticing that guidelines on inflammatory arthritis management had little to say about effects on male fertility, and what they did say had little solid backing. For example, they noted, "the 2020 American College of Rheumatology guideline for the management of reproductive health in rheumatic and musculoskeletal diseases stated that the evidence of recommendations for medical treatment in men was either not graded, or there was no, or low, strength of evidence.... So far, owing to the limited knowledge in this field, recommendations for male patients have been extrapolated from the literature on female reproduction and fertility."

With this evidence desert in mind, the researchers hypothesized that, if inflammatory joint disease impairs male fertility, they should find a signal in national birth and medical records.

Each of the 10,865 men they identified with inflammatory arthritis diagnoses were matched with five other men from the same county and of the same age without such diseases. The age distribution for cases was about as expected, with the largest numbers (approximately 2,300 each) in the 30-39 and 40-49 ranges. There were a handful older than 80, but the researchers cautioned that births prior to 1967 were not registered and hence their offspring might have been undercounted.

About 37% of cases had rheumatoid arthritis, 33% had psoriatic arthritis, and 30% had spondyloarthritis. People with idiopathic juvenile arthritis were excluded. Births were counted from 1967 onward, for a total of 111,246 for cases and controls.

In each age range above 20, childlessness was less common and mean numbers of children were higher in cases versus controls. Sigmo and colleagues said this was mildly surprising, as the lone previous study of male fertility in this population (which was uncontrolled) had suggested a negative effect, and female fertility is definitely impaired.

Another interesting finding was that the disparity in fecundity was seen throughout the 1967-2021 period. That is potentially significant, insofar as medical treatments for inflammatory arthritis shifted substantially over this time. Methotrexate only came into broad use in 1986, and biologics were introduced in 2000. That the difference between cases and controls was apparent in each era suggests that drug effects are not the explanation.

Limitations to the study included reliance on administrative records and the lack of data on many potential confounders.

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    John Gever was Managing Editor from 2014 to 2021; he is now a regular contributor.

Disclosures

The study was funded by Aslaug Anders fond, Astri og Edvard Riisøens legat, Det alminnelige medisinske forskningsfond, Pahles legat, and regional funding from Fagsenter for medisinske kvalitetsregistre i Helse Vest, described as all non-profit organizations.

Authors declared they had no relevant financial interests.

Primary Source

Annals of the Rheumatic Diseases

Sigmo GD, et al "Male patients with inflammatory joint diseases are less likely than controls to be childless: results from a Norwegian population-based cohort study of 10 865 patients" Ann Rheum Dis 2024; DOI: 10.1136/ard-2023-224998.