“50 Shades of sex” under hormonal contraception

Availability of hormonal contraception (HC) has marked the history of gynecological endocrinology promoting reproductive care and prevention of many medical conditions in fertile women. It has been as well a formidable weapon turned against gender inequality breaking new ground in relationships and social roles, even though family planning is an unfinished agenda. The use of HC has driven sexual revolution at multiple levels giving people the possibility to separate sexuality from procreation reliably and to experience pleasure and intimacy in a biopsychosocial perspective [1]. However, health care providers (HCPs) face the challenge of women reporting sexual side effects of HC, which have been proven in some longitudinal studies in conjunction with mood side effects [2,3] and may influence adherence and satisfaction with a given prescription in high-income countries. In spite of the amount of research in this field, mainly pointing at finding differences related to the biochemical characteristics of both estrogens and progestogens, there are still several gaps in our understanding of the impact of HC on sexuality [1]. The majority of studies aimed at capturing the role of changing the hormonal environment in the domains of the sexual response have presented inconclusive results, not allowing at present to draw a clear algorithm for the management of HC-induced sexual dysfunction. This is in line with the evidence that regular cycling women reported normal sexual function measured by the psychometrically validated self-report questionnaire, the Female Sexual Function Index (FSFI), even when circulating androgens displayed a wide range of distribution across the menstrual cycle [4]. Indeed, available evidence indicated that only a minority of women experienced a change in sexual functioning with regard to general sexual response, desire, lubrication, orgasm, and relationship satisfaction and did not necessarily develop female sexual dysfunctions (FSDs) when using HC that block the pre-ovulatory surge of androgens (and estradiol) and reduce the overall steroid hormonal milieu [1]. On the other hand, there was little focus on women’s sexual experiences with contraception in the context of relationships and socio-cultural backgrounds, especially in low- and middle-income countries [5]. Therefore, a standard biopsychosocial model, which is mandatory for valuable research and practice in FSDs, is lacking worldwide in reproductive planning.

A recent systematic review and meta-analysis based on FSFI data included 12 studies involving 9,427 participants using or not using any kind of contraceptive methods [6]. Pooled results did not support a significant difference in the total FSFI scores between groups or an association between contraception use and the risk of FSDs. However, the sexual desire domain showed a significant reduction in women who received contraceptives as compared with nonusers. No significant differences were found in other domains of the sexual response (arousal, lubrication, orgasm, satisfaction, and pain) [6]. Interestingly, in a previous systematic review of the literature (36 studies; 1978–2011; 13,673 women) on the effects of combined oral contraceptives (COCs) on sexual desire, Pastor et al. [7] identified only 15% of COC users reporting low sexual desire. The majority of COC users did not report a significant change and some (n = 1,826) even reported an increase, in conflict with the biologically plausible idea that sexual desire is hampered by lowering free sex steroids (mainly testosterone and possibly estradiol) [1]. Zimmerman et al. [8] showed a mean free testosterone (T) decrease of 61% with a significant increase of the sex hormone binding globulin (SHBG) concentrations during all types of COC use. In addition, suppressive effects on T levels were not different when comparing different types of progestogens, whereas COCs containing second-generation progestogens and/or the lower ethinylestradiol (EE) doses (20–25 mcg) had less impact on SHBG concentrations. It is quite odd that sexual desire was found to decrease only with pills containing 15 mcg EE [6], hence indicating an indirect influence of estrogen-dependent central and peripheral pathways on sexual desire [1]. Even the potential first-choice COC, containing the second-generation progestogen levonorgestrel (LNG) and 30 mcg EE, significantly reduced desire, arousal, and pleasure in comparison to placebo, without influencing overall sexual function and distress [3]. Finally, in a multicenter, randomized, double blind, non-inferiority study, women with COC-associated FSDs received EE 30 mcg/LNG or estradiol valerate (E2V) and dienogest (DNG) for six cycles [9]. Results indicated that switching to either EE/LNG or E2V/DNG was associated with equivalent sexual improvements, including the increased sum of FSFI desire and arousal component scores. This study challenged the perception that COCs containing anti-androgenic progestogens, such as DNG, have a detrimental effect on sexual function relative to those containing androgenic progestogens, such as LNG [9].

Notwithstanding, the androgen dilemma in sexual desire [10] is still a work in progress and there is some hope that innovation in HC (new compounds, routes and regimens, as well as addition of androgens, i.e. DHEA, or other antidotes) will fill the gap of the ‘50 shades of sex’ emerging from women-centered counseling in real-life practice. Double blind, randomized, placebo-controlled trials will be undoubtedly important, but a careful multidimensional (psychological, sexual, and relational) assessment will be equally relevant at first prescription to evaluate eventual sexual effects of HC at follow-up.

Disclosure statement

Rossella Nappi: Past financial relationships (lecturer, member of advisory boards and/or consultant) with Boehringer Ingelheim, Ely Lilly, Endoceutics, Gedeon Richter, HRA Pharma, Procter & Gamble Co, TEVA Women’s Health Inc and Zambon SpA. At present, she has an ongoing relationship with Astellas, Bayer HealthCare AG, Exceltis, Fidia, Merck Sharpe & Dohme, Novo Nordisk, Palatin Technologies, Pfizer Inc, Shionogi Limited and Theramex.

Lara Tiranini: no conflicts of interest.