Hormonal contraceptives (HCs) have been life-changing for generations of women. Giving women the ability to better control the timing of pregnancy and childbirth has allowed them to set long-term educational and career goals, making them an important tool in women’s upward social and economic mobility (Bailey, 2006, Goldin and Katz, 2002). HCs also offer non-contraceptive benefits to women, including reduced risk of ovarian cancer (Hannaford et al., 2007, Maia and Casoy, 2008, Tworoger et al., 2007, Vessey and Painter, 2006), reductions in heavy or painful menstrual bleeding (Stewart and Black, 2015), and improvements in premenstrual symptoms (e.g., PMS; e.g., Bertone-Johnson et al., 2014, Ito et al., 2021, Koci and Strickland, 2007) and the appearance of acne (Arowojolu et al., 2012).

Box 1. Abbreviations of Key TermsDespite the benefits of HC use, some women are reluctant to use HCs or discontinue use because of concerns with unwanted side-effects (Hatcher et al., 2004, Ott et al., 2008). Nearly half of all women who go on HCs stop using them within the first year because of intolerable side-effects, particularly those affecting mood or sexual function (Sanders et al., 2001). Further, side effect concerns represent a frequently-cited reason that women resist beginning HC use in the first place (Le Guen et al., 2021), a trend that has been exacerbated in recent years by social media testimonials from women publicizing their negative experiences with HCs (Kissling, 2016, Le Guen et al., 2021, Vondráčková, 2020) and their decision to stop using them (Kissling, 2014). There has been a 9% decline in use of HCs in the US in the last fifteen years (Women’s Health Policy, 2019), suggesting that women may be increasingly wary of hormonal forms of contraception because of its possible side-effects.

Although women are frequently concerned with HC side effects (Le Guen et al., 2021), researchers often fail to find differences between HC-treated and HC-untreated (i.e., naturally cycling [NC]) women when it comes to specific outcomes believed to be linked to HC use (e.g., weight gain, depression). The lack of mean differences between users and non-users has led many researchers and clinicians to conclude that HCs have relatively few side-effects, despite individual women’s reports of having experiencing them. However, given the tremendous amount of heterogeneity in women’s responses to HC treatment, such conclusions may be premature. While it may be true that many women may not experience some of the side-effects believed to be linked to HC treatment, others do. Understanding the sources of variability in women’s responses to HC treatment therefore represents an important research opportunity for those hoping to conduct research that can translate from the laboratory to the clinic.

In the following, we provide recommendations for programs of research that promise to offer essential insight into the factors that impact women’s experiences with HC side-effects, with a specific focus on those that are psychobehavioral in nature. In particular, we focus on research questions addressing woman- and prescription- specific factors that may impact women’s positive or negative experiences with different HC regimens. With this goal in mind, we first review research demonstrating person- and prescription- based heterogeneity in women’s psychobehavioral responses to HCs. Next, we identify several promising person- and prescription- based sources of this heterogeneity that warrant future research. We close with a discussion of research approaches that are particularly well-suited to such questions and identify ways that researchers can make their results maximally impactful on clinical practice.