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OBJECTIVES: To determine indirectly the effect of changes in levels of reproductive hormones on CD4 lymphocyte counts by investigating the impact of pregnancy and menopause on CD4 lymphocyte counts in HIV-infected women. METHODS: Participants were 382 women with a known interval of HIV seroconversion. Review of questionnaires or patient charts provided information on pregnancy and menopause. A linear regression model with a random intercept and slope, which adjusts for multiple CD4 lymphocyte counts per woman, was applied to estimate the CD4 decline following HIV seroconversion and to evaluate the effect of pregnancy and menopause on the CD4 path. RESULTS: The 382 women had a median age of 25 years at seroconversion and yielded 1428 CD4 lymphocyte counts from 3 to 10 years after seroconversion. At 3 years from seroconversion, 20 women had passed the menopause (i.e., the last menses) and five more subsequently passed this point during follow-up; 25 women had a pregnancy after study entry. Postmenopausal women had lower CD4 lymphocyte counts 3 years after seroconversion than premenopausal women (333 vs 399 x 106 cells/l; P = 0.09), and pregnant women had lower counts than non-pregnant women (375 vs 399 x 106 cells/l; P = 0.36). The monthly CD4 decline was not associated with pregnancy and menopause. Adjustment for age did not change the results. CONCLUSIONS: The results suggest that CD4 lymphocyte counts differ between pre- and postmenopausal women, perhaps because of changes in the level of reproductive hormones in the menopause, but associations were not statistically significant. Pregnancy had no statistically significant effect on CD4 lymphocyte counts.