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  • Presidential Address Gout in Women: A Historical Perspective
  • Thomas G. Benedek (bio)

The accuracy of an observation depends on the intellect of the observer as modified by cultural forces and, more recently, also the quality of aids to observation: chemical, physical, or statistical. The demand for an explanation of observations appears to be a basic human characteristic, but what is acceptable as an explanation also reflects a given culture. The observation with which I want to exemplify these premises is that gout rarely occurs in women. Gout was the first nongenital disease that was recognized to occur predominantly in one sex. Until the end of the nineteenth century, several decades into the dawning of modern metabolic concepts, two ancient judgments were tediously reiterated: a dispassionate conclusion from the fourth century B.C., and an impassioned opinion from the first century A.D. Chronologically, these are our starting points; but to provide a frame of reference, I shall first outline the development of the current understanding of why, indeed, gout occurs in far fewer women than men.

Prerequisite to the occurrence of gouty joint inflammation there is either a metabolic abnormality that results in the overproduction of uric acid, or a renal abnormality that causes its inadequate excretion. This was already hypothesized by Alfred B. Garrod (1819–1909) in 1854 [End Page 1] London, a mere six years after he had devised the first test for the detection of uric acid in the blood of gouty patients. 1 Dyce Duckworth (1840–1928), the other English gout expert of the time, in 1889 stated simply: “No uric acid, no gout.” 2 That uric acid is a normal component of blood was first demonstrated in 1912, 3 but it was not until the late 1930s that analytical techniques became sufficiently sensitive for the gender-related difference in the uric acid content to be recognized. 4 Consequently, the diagnosis of gout was based mainly on the individual notions of physicians. A physician at the rheumatism center in Bath called attention to this in 1920, questioning reports that more than 15% of cases occur in women:

in many of these cases the assumed gouty inflammation resolves itself into one of inflamed bunion. In but too many instances, women, showing Heberden’s nodes, are held to have gout or “rheumatic gout.” . . . having regard to the fact that the diagnosis of gout in women is frequently based on so-called “masked and irregular manifestations,” . . . statistics purporting to indicate the percentage of gout in women and men, are not very convincing. 5

Statistics from the Royal Devonshire Rheumatism Hospital bear evidence to the subjectivity of the diagnosis: in five-year periods between 1896 and 1935 the frequency of gout varied by more than 100%, and the proportion of gouty women, nearly sixfold. The introduction of a blood test for uric acid resulted in a reduction of the proportion of women from 34.3% to a still doubtful 18.0%. 6

About 5% of cases of primary gout are currently believed to occur in [End Page 2] women. 7 The disease as such is now clearly defined. 8 The modern diagnostic uncertainty stems from the recognition that certain medications and diseases may cause gout secondarily. 9

The higher the concentration of uric acid in the blood, the greater is the possibility of an attack of gouty inflammation. However, no matter what the concentration is, why an attack occurs on a certain day, or at all, remains unproven. A curious difference between men and women is that the uric acid content of the blood of healthy women rises toward, but usually does not reach, the more stable male value after the menopause. According to a large survey in Michigan, the sex difference in the 25–29 year age group was 31% (5.25 vs. 4.00 mg/DL), while in the 55–59 year age group the difference was 16% (5.43 vs. 4.67 mg/DL). 10 Curiously, the uric acid content of the blood of gouty women tends to exceed that in gouty men—according to Puig and his colleagues, by about 11%. 11

The explanation of the gender difference appears to lie in the efficiency with which...

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