Dataset Information

Mechanistic model of hormonal contraception.

ABSTRACT: Contraceptive drugs intended for family planning are used by the majority of married or in-union women in almost all regions of the world. The two most prevalent types of hormones associated with contraception are synthetic estrogens and progestins. Hormonal based contraceptives contain a dose of a synthetic progesterone (progestin) or a combination of a progestin and a synthetic estrogen. In this study we use mathematical modeling to understand better how these contraceptive paradigms prevent ovulation, special focus is on understanding how changes in dose impact hormonal cycling. To explain this phenomenon, we added two autocrine mechanisms essential to achieve contraception within our previous menstrual cycle models. This new model predicts mean daily blood concentrations of key hormones during a contraceptive state achieved by administering progestins, synthetic estrogens, or a combined treatment. Model outputs are compared with data from two clinical trials: one for a progestin only treatment and one for a combined hormonal treatment. Results show that contraception can be achieved with synthetic estrogen, with progestin, and by combining the two hormones. An advantage of the combined treatment is that a contraceptive state can be obtained at a lower dose of each hormone. The model studied here is qualitative in nature, but can be coupled with a pharmacokinetic/pharamacodynamic (PKPD) model providing the ability to fit exogenous inputs to specific bioavailability and affinity. A model of this type may allow insight into a specific drug's effects, which has potential to be useful in the pre-clinical trial stage identifying the lowest dose required to achieve contraception.

SUBMITTER: Wright AA

PROVIDER: S-EPMC7365466 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Mechanistic model of hormonal contraception.

Wright A Armean AA Fayad Ghassan N GN Selgrade James F JF Olufsen Mette S MS

PLoS computational biology 20200629 6

Contraceptive drugs intended for family planning are used by the majority of married or in-union women in almost all regions of the world. The two most prevalent types of hormones associated with contraception are synthetic estrogens and progestins. Hormonal based contraceptives contain a dose of a synthetic progesterone (progestin) or a combination of a progestin and a synthetic estrogen. In this study we use mathematical modeling to understand better how these contraceptive paradigms prevent o ...[more]

PMID: 32598357

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Project description:ObjectivesNew Mexico is a large rural state with high rates of unintended pregnancy and limited access to contraception. In 2017, the New Mexico Pharmacist Prescriptive Authority Act was amended to allow pharmacists to prescribe hormonal contraception. We explored pharmacist perspectives on prescribing hormonal contraceptives, including perceived barriers and facilitators to implementation in rural New Mexico and opinions on over-the-counter (OTC) access, and prescribing and inserting subdermal contraceptive implants.MethodsThis qualitative study recruited rural pharmacists using contact information from the New Mexico Board of Pharmacy and at a state-level pharmacist conference. We conducted semistructured telephone interviews with pharmacists focusing on benefits and concerns about prescribing hormonal contraception, resources required, perspectives on OTC access, and interest in prescribing and placing contraceptive implants. Deidentified transcribed interviews were analyzed by 2 independent coders for emerging themes.ResultsFrom November 2017 to January 2018, we recruited 25 rural pharmacists and conducted 21 interviews. The majority of participants were male (71%), aged over 60 years (43%), and in practice for over 20 years (52%). Interviewees were mostly positive about prescribing hormonal contraception citing community benefits. The top 3 perceived barriers were training needs, reimbursement, and liability. The top 3 facilitators were the availability of private areas within pharmacies, pharmacists' role as knowledgeable health care team members, and pharmacist accessibility without appointments. Most pharmacists did not support OTC access to hormonal contraception, and over half were interested in certification to prescribe and place subdermal contraceptive implants.ConclusionNew Mexico pharmacists identified community benefits of pharmacy access to hormonal contraception and were interested in training. Several barriers must be addressed to realize the potential of this practice expansion.

Project description:To compare etonogestrel pharmacokinetic and pharmacodynamic outcomes by both self-reported race/ethnicity and genetically determined ancestry among contraceptive implant users. We conducted a secondary analysis of our parent pharmacogenomic study of 350 implant users. We genotyped these reproductive-aged (18-45 years) women for 88 ancestry-informative single nucleotide polymorphisms. We then assigned each participant a proportion value for African (AFR), European (EUR), and Indigenous American (AMR) ancestry based on reference population data. We correlated genetic ancestry with self-reported race/ethnicity and utilized genetic ancestry proportion values as variables for previously performed association analyses with serum etonogestrel concentrations and progestin-related side effects (e.g., bothersome bleeding and subjective weight gain). We successfully estimated genetically determined ancestry for 332 participants. EUR, AFR, and AMR ancestry were each highly correlated with self-reported White/non-Hispanic race (r = 0.64, p = 4.14 × 10-40 ), Black/African American race (r = 0.88, p = 1.36 × 10-107 ), and Hispanic/Latina ethnicity (r = 0.68, p = 4.03 × 10-47 ), respectively. Neither genetically determined ancestry nor self-reported race/ethnicity were significantly associated with serum etonogestrel concentrations. AFR ancestry and self-reported Black race had similar associations with reporting monthly periods (odds ratio [OR] 2.18, p = 0.09 vs. OR 2.22, p = 0.02) and having received treatment for bothersome bleeding (OR 5.19, p = 0.005 vs. OR 4.73, p = 2.0 × 10-4 ). In multivariable logistic regression for subjective weight gain, AMR ancestry dropped out of the model in preference for self-reported Hispanic/Latina ethnicity. We found no new associations between genetically determined ancestry and contraceptive implant pharmacodynamics/pharmacokinetics. Self-reported race/ethnicity were strong surrogates for genetically determined ancestry among this population of contraceptive implant users. Our data suggest that self-reported race/ethnicity, capturing societal and cultural aspects, remain important to the investigation of progestin-related side effects.

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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Mechanistic model of hormonal contraception.

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Mechanistic model of hormonal contraception.

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