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Oral contraceptive pill (OC) is one of the most popular form of contraception. Despite both behavioral and neuroimaging evidence of its significant impact on female brain and cognitive functions, much remains to be discovered regarding OCs targets in the brain and mechanisms of action. In the present study mental rotation performance was compared between women using anti-androgenic oral contraceptives (n = 35), naturally cycling (NC) women (n = 33) and men (n = 29). On average, OC users were less accurate than NC women and men. Men performed the task more accurately than NC women, but the difference reached significance only in the highest angular disparity condition (150 deg). The response time was positively related with progesterone level while accuracy was negatively related with 17ß-estradiol level, in NC, but not OC women. The comparison of slope and intercept values (parameters relating response time to angular disparity) revealed the main result of present study: OC users exhibited significantly lower slope compared to men and NC women, but there were no differences in intercept between groups. These results suggest that OC users instead of using rotation in mind strategy implemented some alternative method(s). We conclude that lower performance accuracy of OC users could be related to a less efficient performance strategy.The effect of oral contraceptives (OC) on mental rotation performance was assessed.OC users were less accurate than nonusers or men.Flat slopes of response time indicate non-rotational strategy in OC users.Level of sex steroids, especially estradiol, was still high in some OC users.Progesterone and estradiol affected performance of nonusers, but not OC users.