A rat model of oral hormonal contraception: Effects on drug preference and gonadal function.

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Gonadal hormones (e.g., estradiol and progesterone) influence response to, and preference for, drugs in females; however, how hormonal contraceptives, synthetic hormones that decrease gonadal hormone levels, affect drug preference is not known. The current experiment investigated whether oral administration of levonorgestrel (LNG), a synthetic progestin used in hormonal contraceptives, would lead to a reduction in amphetamine (AMPH) preference. Female rats were tested for their AMPH preference over 3 days (which also served as extinction sessions) after receiving oral administration of LNG (250 μg, 500 μg, or 2 mg) or during an estrous cycle stage associated with higher levels of gonadal hormones (i.e., proestrus/estrus). Our results show that AMPH preference was reduced for females on 500 μg and 2 mg of LNG across extinction sessions. Interestingly, only the 2 mg LNG dose led to a disruption in the naturally occurring estrous cycle. Uterine horn width, an index of estrogen exposure, was decreased in all LNG groups, but only the 500 μg and 2 mg LNG groups showed suppression of gonadal hormones, suggesting that both doses are sufficient for contraceptive use in rats. Our study demonstrates an effective and noninvasive oral LNG administration method in a rat model and further shows reduced AMPH preference by LNG. (PsycInfo Database Record (c) 2025 APA, all rights reserved).

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ObjectiveResearchers traditionally rely on participant self-report for contraceptive use. We hypothesized that self-reported contraceptive use by clinical research participants may disagree with objectively measured hormonal status. Study designWe enrolled women in Harare, Zimbabwe, aged 18–34, who by self-report had not used hormonal or intrauterine contraception for >30 days, or depot medroxyprogesterone acetate for >10 months, into a study designed to assess biologic changes with contraceptive initiation and use. Blood samples obtained at enrollment and each follow-up visit (N=1630 from 447 participants) were evaluated by mass spectrometry for exogenous hormones. We individually interviewed a subset of participants (n=20) with discrepant self-reported and measured serum hormones to better understand nondisclosure of contraceptive use. ResultsDiscrepant with self-reported nonuse of hormonal contraception, synthetic progestogens were detectable in 120/447 (27%, 95% confidence interval 23%–31%) enrolled women. Measured exogenous hormones consistent with use of contraceptive pills (n=102), injectables (n=20) and implants (n=3) were detected at enrollment, with 7 women likely using >1 contraceptive. In-depth interviews revealed that participants understood the requirement to be hormone free at enrollment (100%). Most (85%) cited partner noncooperation with condoms/withdrawal and/or pregnancy concerns as major reasons for nondisclosed contraceptive use. All interviewed women (100%) cited access to health care as a primary motivation for study participation. Of participants who accurately reported nonuse of hormonal contraception at enrollment, 41/327 (12.5%) had objective evidence of nonstudy progestin use at follow-up that disagreed with self-reported nonuse. ConclusionsWomen joining contraceptive research studies may misrepresent their use of nonstudy contraceptive hormones at baseline and follow-up. Objective measures of hormone use are needed to ensure that study population exposures are accurately categorized. Implications statementAmong Zimbabwean women participating in a contraceptive research study, 27% had objective evidence of use of nonstudy contraceptives at enrollment that disagreed with self-report. Studies that rely on self-report to identify contraceptive hormone exposure could suffer from significant misclassification.

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