Reproductive Health in Xeroderma Pigmentosum: Features of Premature Aging

Abstract

Objective: To assess the age at menarche and menopause of women with xeroderma pigmentosum, a DNA repair disease with premature aging, in a longitudinal natural history study.

Methods: We conducted a natural history study that reviewed medical records for gynecologic and reproductive health of all female patients with xeroderma pigmentosum aged older than 9 years examined at the National Institutes of Health (NIH). We performed gynecologic and laboratory examinations on a subset of the patients. Women in a second subset, who could not be examined, were interviewed using a questionnaire. Women who were deceased or lost to follow-up formed a third subset.

Results: Sixty females with xeroderma pigmentosum aged older than 9 years (median 29 years, range 10-61 years) were evaluated at the NIH from 1971 to 2018. Of these 60, 31 had history, questionnaire, record review, and gynecologic evaluation; 14 had record review and questionnaire interview by telephone; and 15 had only NIH record review. Menarche in females with xeroderma pigmentosum occurred at a median age of 12.0 years (range 9-17 years), which was comparable with the U.S. general population. Among the 18 patients with menopause, the median age at menopause of 29.5 years (range 18-49.5 years) was more than 20 years younger than in the U.S. general population (52.9 years). Premature menopause (before age 40 years) occurred in 14 of the 45 (31%) women aged 18 years or older, and primary ovarian insufficiency was documented in nine of them. There were 32 live births among 21 of the women, five of whom subsequently developed premature menopause.

Conclusion: Females with xeroderma pigmentosum in our study had a normal age at menarche and were fertile but had increased incidence of premature menopause. Premature menopause, a symptom of premature aging, should be considered for gynecologic and reproductive health as well as implicating DNA repair in maintaining normal ovarian function.

Clinical trial registration: ClinicalTrials.gov, NCT00001813.

Figure 1.

Age distribution and age of menopause of women with xeroderma pigmentosum. A. There were 18 women who had menopause and 14 of them (78%) had premature menopause (before 40 years of age). B. There were 39 women aged 10 to 52 years who were still menstruating.

Figure 2.

Comparison of age at menarche in 56 women with xeroderma pigmentosum (solid curve) to 1,302 women in the U.S. general population (dashed curve). There was a similar median age of 12.0 years in both groups. (U.S. General population data from McDowell MA, Brody DJ, Hughes JP. Has age at menarche changed? Results from the National Health and Nutrition Examination Survey (NHANES) 1999-2004. J Adolesc Health 2007 Mar;40(3):227-31.).

Figure 3.

Comparison of ages of the proportion of women undergoing menopause in the xeroderma pigmentosum patient group (n=18) to the ages of the proportion of women undergoing menopause in the U.S. general population (n=1,533). The women with xeroderma pigmentosum reached menopause about 20 years earlier than the Caucasian controls (median 29.5 years compared with 52.9 years). (U.S. General population data from Gold EB, Crawford SL, Avis NE, Crandall CJ, Matthews KA, Waetjen LE, et al. Factors related to age at natural menopause: longitudinal analyses from SWAN. Am J Epidemiol 2013 Jul 1;178(1):70-83.).