Combined oral contraceptive pill

Summary

The combined oral contraceptive pill (COCP), often referred to as the birth control pill or colloquially as "the pill", is a type of birth control that is designed to be taken orally by women. The pill contains two important hormones: a progestin (a synthetic form of the hormone progestogen/progesterone) and estrogen (usually ethinylestradiol or 17β estradiol). When taken correctly, it alters the menstrual cycle to eliminate ovulation and prevent pregnancy. COCPs were first approved for contraceptive use in the United States in 1960, and remain a very popular form of birth control. They are used by more than 100 million women worldwide and by about 9 million women in the United States. From 2015 to 2017, 12.6% of women aged 15–49 in the US reported using COCPs, making it the second most common method of contraception in this age range (female sterilization is the most common method). Use of COCPs, however, varies widely by country, age, education, and marital statu

Official source

https://en.wikipedia.org/wiki/Combined_oral_contraceptive_pill

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Estrogen receptor signaling in the human breast epithelium

Céline Berthe Constantin

Breast cancer is the most diagnosed malignancy in women worldwide, making effective prevention strategies crucial. Hormonal contraceptives, consisting of a synthetic progesterone receptor agonist alone or in combination with an estrogen, are used by millions of women worldwide and have been linked to increased breast cancer risk. To date, their mechanisms of action on human breast epithelial cells (HBECs) remain elusive. We have previously shown that the mouse intraductal model in which HBECs are grafted to the milk ducts of immunocompromised mice preserves hormone receptor expression. We exploited this model to assess if 17alpha-ethinyl estradiol (EE2), the predominant estrogenic component of combined oral contraceptives (OCs), has a distinct activity profile from that of the natural estrogen 17beta-estradiol (E2) in HBECs and characterized methods for stable and long-term estrogen delivery.We show that both E2 and EE2 increased the in vivo growth of HBECS, with the former estrogen being slightly more potent. E2 and EE2-treated glands showed similar proliferation indices 21 days after treatment and displayed similar transcriptomic profiles with robust gene signatures. Our data suggest that the increased risk of breast cancer associated with the use of OCs is not attributed to EE2, but rather to the progestin used in combination. We recently showed that progestins with androgenic properties promote HBEC proliferation but progestins with anti-androgenic properties do not.

EPFL2022

A high resolution LC-MS targeted method for the concomitant analysis of 11 contraceptive progestins and 4 steroids

Alexandre Béguin, Cathrin Brisken, Fabio De Martino, Csaba Ferenc László, Marc Moniatte, Jonathan Paz Montoya, Marie Shamseddin

In the context of hormonal contraception and hormone replacement therapy (HRT), many women are exposed to exogenous hormones. Current use of hormonal contraception with combined ethinyl estradiol and different progestins bestows a breast cancer relative risk (RR) of 1.2-while combined HRT has a RR of 2. Although these exposures present an important public health issue, little is known about the effects of individual progestins on the breast and other tissues. Increasing availability of large scale biobanks, high throughput analyses and data management tools enable ever expanding, sophisticated population studies. In order to address the impact of distinct progestins on various health indicators, it is desirable to accurately quantify progestins in clinical samples. Here we have developed and validated a high resolution liquid chromatography mass spectrometry (LC-MS) targeted method for the simultaneous quantification of 11 synthetic progestins widely used in oral contraceptives, gestodene, levonorgestrel, etonogestrel, chlormadinone acetate, cyproterone acetate, drospirenone, desacetyl norgestimate, medroxyprogesterone acetate, norethindrone, dienogest, nomegestrol acetate, and 4 endogenous steroid hormones, progesterone, testosterone, androstenedione, and cortisol in blood samples. This highly specific quantitative analysis with high resolution Orbitrap technology detects and quantifies 15 compounds using their internal standard counterparts in a single 12 min LC-MS run. Sensitivity is attained by the use of the instrument in targeted selected ion monitoring mode. Lower limit of quantitation ranges from 2.4 pg/ml for drospirenone to 78.1 pg/ml for chlormadinone acetate. The method provides comprehensive progestin panel measurements with as little as 50 pi of murine or human plasma. (C) 2019 The Authors. Published by Elsevier B.V.

2019

In the past decades, polymeric nanoparticles have emerged as a most promising and viable technology platform for targeted and controlled drug delivery. As vehicles, ideal nanoparticles are obliged to possess high drug loading levels, deliver drug to the specific pathological site and/or target cells without drug leakage on the way, while rapidly unload drug at the site of action. To this end, various "intelligent" polymeric nanoparticles that release drugs in response to an internal or external stimulus such as pH, redox, temperature, magnetic and light have been actively pursued. These stimuli-responsive nanoparticles have demonstrated, though to varying degrees, improved in vitro and/or in vivo drug release profiles. In an effort to further improve drug release performances, novel dual and multi-stimuli responsive polymeric nanoparticles that respond to a combination of two or more signals such as pH/temperature, pH/redox, pH/magnetic field, temperature/reduction, double pH, pH and diols, temperature/magnetic field, temperature/enzyme, temperature/pH/redox, temperature/pH/magnetic, pH/redox/magnetic, temperature/redox/guest molecules, and temperature/pH/guest molecules have recently been developed. Notably, these combined responses take place either simultaneously at the pathological site or in a sequential manner from nanopartide preparation, nanopartide transporting pathways, to cellular compartments. These dual and multi-stimuli responsive polymeric nanoparticles have shown unprecedented control over drug delivery and release leading to superior in vitro and/or in vivo anti-cancer efficacy. With programmed site-specific drug delivery feature, dual and multi-stimuli responsive nanoparticulate drug formulations have tremendous potential for targeted cancer therapy. In this review paper, we highlight the recent exciting developments in dual and multi-stimuli responsive polymeric nanoparticles for precision drug delivery applications, with a particular focus on their design, drug release performance, and therapeutic benefits. (C) 2013 Elsevier Ltd. All rights reserved.

Elsevier Sci Ltd2013

A high resolution LC-MS targeted method for the concomitant analysis of 11 contraceptive progestins and 4 steroids

Alexandre Béguin, Cathrin Brisken, Fabio De Martino, Csaba Ferenc László, Marc Moniatte, Jonathan Paz Montoya, Marie Shamseddin

2019