The effect of combined oral contraception on testosterone levels in healthy women: a systematic review and meta-analysis

Abstract

BACKGROUNDCombined oral contraceptives (COCs) reduce levels of androgen, especially testosterone (T), by inhibiting ovarian and adrenal androgen synthesis and by increasing levels of sex hormone-binding globulin (SHBG). Although this suppressive effect has been investigated by numerous studies over many years, to our knowledge no systematic review concerning this issue had been performed. This systematic review and meta-analysis was performed to evaluate the effect of COCs on concentrations of total T, free T and SHBG in healthy women and to evaluate differences between the various types of COCs (e.g. estrogen dose, type of progestin) and the assays used to assess total T and free T.METHODSA review of the literature was performed using database searches (MEDLINE, EMBASE and the Cochrane Central Register of Clinical Trials) and all publications (from inception date until July 2012) investigating the effect of COCs on androgen levels in healthy women were considered eligible for selection. Three reviewers were involved in study selection, data extraction and critical appraisal. For the meta-analysis, data on total T, free T and SHBG were extracted and combined using random effects analysis. Additional subgroup analyses were performed to evaluate differences between the various types of COCs (e.g. estrogen dose, type of progestin) and the assays used to assess total T or free T.RESULTSA total of 151 records were identified by systematic review and 42 studies with a total of 1495 healthy young women (age range: 18–40 years) were included in the meta-analysis. All included studies were experimental studies and 21 were non-comparative. Pooling of the results derived from all the included papers showed that total T levels significantly decreased during COC use [mean difference (MD) (95% confidence interval, CI) −0.49 nmol/l (−0.55, −0.42); P < 0.001]. Significantly lower levels of free T were also found [relative change (95% CI) 0.39 (0.35, 0.43); P < 0.001], with a mean decrease of 61%. On the contrary, SHBG concentrations significantly increased during all types of COC use [MD (95% CI) 99.08 nmol/l (86.43, 111.73); P < 0.001]. Subgroup analyses revealed that COCs containing 20–25 µg EE had similar effects on total and free T compared with COCs with 30–35 µg EE. In addition, suppressive effects on T levels were not different when comparing different types of progestins. However, subgroup analyses for the estrogen dose and the progestin type in relation to changes in SHBG levels did show significant differences: COCs containing second generation progestins and/or the lower estrogen doses (20–25 µg EE) were found to have less impact on SHBG concentrations.CONCLUSIONSThe current literature review and meta-analysis demonstrates that COCs decrease circulating levels of total T and free T and increase SBHG concentrations. Due to the SHBG increase, free T levels decrease twice as much as total T. The estrogen dose and progestin type of the COC do not influence the decline of total and free T, but both affect SHBG. The clinica...

A longitudinal analysis of women’s salivary testosterone and intrasexual competitiveness

“…By contrast with this prediction, we observed only an effect of testosterone in the current study, suggesting that our results are not simply due to the effects of experiencing intrasexual competition on hormone levels. Our proposal that our results are more likely to reflect the effects of testosterone on intrasexual competitiveness (rather than vice versa) is also supported by Cobey et al's (2013) results indicating that partnered women's intrasexual competitiveness decreased once they started using hormonal contraceptives, which would lower their testosterone levels (Zimmerman et al, 2014). It is also consistent with research reporting that exogenous testosterone increases intrasexual competitiveness in female birds and rats (e.g., Albert et al, 1990;Zysling et al, 2006).…”

“…Moreover, intrasexual competitiveness did not differ between these late-follicular or mid-luteal phases. Since hormonal contraceptive use lowers testosterone levels in women (Zimmerman et al, 2014) and evidence that testosterone levels change between the late-follicular and mid-luteal phases is mixed (Dabbs, 1990;Dabbs & de La Rue, 1991; see also Caruso et al, 2014), Cobey et al (2013) speculated that the observed changes in women's intrasexual competitiveness may be a consequence of changes in their testosterone levels. Indeed, this explanation would be consistent with findings showing that women's testosterone levels increased after they imagined their partner flirting with an attractive woman (Ritchie & van Anders, 2014) or were exposed to olfactory cues associated with ovulation in other women (Maner & McNulty, 2013).…”

A perspective on current research investigating the effects of hormonal contraceptives on determinants of female athlete performance

“…A recent meta-analysis showed that OC use reduced free testosterone by 61% compared to non-users 44 , possibly due to an increase in sex hormone binding globulin concentration, which binds to testosterone rendering it inactive. OC use increases GH concentrations [45][46] with second (30 µg EE and 0.125 mg Levonorgestrel) and fourth generation (30 µg EE and 2 mg Dienogest) OCs reducing concentrations of IGF-1, but not a ecting IGF binding protein-1 concentrations 45 .…”

Restoring testosterone levels by adding dehydroepiandrosterone to a drospirenone containing combined oral contraceptive: II. Clinical effects

“…In addition, we have shown earlier that a dose of 50 mg DHEA could normalize free T levels in combination with a COC containing the progestin levonorgestrel (LNG) [53]. COCs containing LNG hardly increase SHBG [19] and therefore, the clinical effect of androgen restoration in users of an EE/LNG COC by adding 50 mg DHEA may be more pronounced. For those COCs that increase SHBG, a higher dose of DHEA may be required to normalize free T and demonstrate clinical effects.…”

“…COCs are known to reduce androgen levels, especially T [19,20], although no consistent effect on mood and sexual function has been observed [3,[21][22][23][24][25][26]. However, reduced androgen levels may be an important factor contributing to COC-associated sexual dysfunction and mood complaints [27,28].…”