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Characterisation of progestins used in hormonal contraception and progesterone via the progesterone receptor.

ABSTRACT: Different progestogens are widely used in hormonal therapy and mediate their therapeutic actions via the progesterone receptor (PR). Little published data exist on their relative efficacies and potencies via the PR, while those available may be confounded by off-target receptors, different methodologies and model systems. We performed dose-response analysis to investigate the efficacies and potencies for transcription of progesterone and several progestins widely used in contraception via the B isoform of human PR (PR-B). We compared responses using three different cell lines and two different transient transfection conditions. Results show that in vitro biological responses via PR-B for the select progestogens can vary significantly in biocharacter, rank order and absolute values for efficacies and potencies, depending on the cell line and transfection condition. Progestogen rank orders for published relative binding affinities are mostly different to those for relative efficacies and potencies. These in vitro differences suggest that rank orders and absolute values of the efficacies and potencies of the progestogens are likely to vary in vivo in a cell-specific and progestogen-specific manner, and cannot easily be extrapolated from in vitro data, as is usually the practice. While obtaining such data in vivo is not possible, these in vitro data show proof of concept for likely significant cell- and progestogen-specific PR-B effects.

SUBMITTER: Enfield K

PROVIDER: S-EPMC8129485 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Importance:Since 2016, 11 states have expanded the scope of pharmacists to include direct prescription of hormonal contraception. Dispensing greater than 1 month's supply is associated with improved contraceptive continuation rates and fewer breaks in coverage. Scant data exist on the practice of pharmacist prescription of contraception and its outcomes compared with traditional, clinic-based prescriptions. Objective:To compare the amount of hormonal contraceptive supply dispensed between pharmacists and clinic-based prescriptions. Prescribing patterns were assessed by describing prescribing practices for women with contraindications to combined hormonal contraception. Characteristics of women seeking hormonal contraception directly from pharmacists were also described. Design, Setting, and Participants:This cohort study surveyed women aged 18 to 50 years who presented to pharmacies in California, Colorado, Hawaii, and Oregon for hormonal contraception prescribed by a clinician or a pharmacist between January 30 and November 1, 2019. Exposures:Pharmacist or clinic-based prescription of contraception. Main Outcomes and Measures:Months of contraceptive supply dispensed. Results:Four hundred ten women (mean [SD] age, 27.1 [7.7] years) were recruited who obtained contraception directly from a pharmacist (n?=?144) or by traditional clinician prescription (n?=?266). Women obtaining contraception from a pharmacist were significantly younger (82 [56.9%] vs 115 [43.2%] participants aged 18-24 years; P?=?.03), had less education (38 [26.4%] vs 100 [37.6%] with a bachelor degree; P?=?.002), and were more likely to be uninsured (16 [11.1%] vs 8 [3.0%] participants; P?=?.001) compared with women with a prescription from a clinician. Pharmacists were significantly more likely to prescribe a 6-month or greater supply of contraceptives than clinicians (6.9% vs 1.5%, P?<?.001) and significantly less likely to only prescribe a 1-month supply (42 [29.2%] vs 118 [44.4%] prescriptions; P?<?.001). Controlling for all covariates, women seen by pharmacists had higher odds of receipt of a 6-month or greater supply of contraceptives compared with those seen by clinicians (odds ratio?=?3.55; 95% CI, 1.88-6.70). Pharmacists were as likely as clinicians to prescribe a progestin-only method to women with a potential contraindication to estrogen (n?=?60 women; 8 [20.0%] vs 6 [30.0%], P?=?.52). Conclusions and Relevance:These findings suggest that pharmacist prescription of contraception may be associated with improved contraceptive continuation by preventing breaks in coverage through the provision of a greater supply of medication. Efforts are needed to educate prescribing providers on the importance of dispensing 6 months or greater contraceptive supply.

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Characterisation of progestins used in hormonal contraception and progesterone via the progesterone receptor.

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