By Aly W. | First published January 9, 2020 | Last modified March 1, 2021
Based on anecdotal experience, some people in the transfeminine community believe that progesterone has positive effects on sexual desire. In addition, some researchers have theorized that progesterone may be positively involved in sexual desire in women (Regan, 1998). Some people have also argued that the neurosteroid metabolites of progesterone like allopregnanolone and pregnanolone might provide special benefits on sexual desire that are not shared with progestins. I’ve reviewed the available evidence and literature to assess whether progesterone or other progestogens indeed improve sexual desire function in women and might be useful for this in transfeminine people.
Progesterone levels are strongly and consistently negatively associated with female sexual desire and behavior in most animal species (Roney, 2015). This includes in monkeys and apes (Roney, 2015).
Progesterone, both alone and when added to an estrogen, has been shown to inhibit sexual behavior and receptivity in female monkeys in many studies (Luttge, 1971; Baum et al., 1976; Baum et al., 1977; Michael et al., 1967). This inhibition is often marked. Likewise, subcutaneous implants of progesterone were shown to suppress sexual behavior in testosterone-treated castrated male monkeys (Zumpe, Clancy, & Michael, 1997). As the male monkeys were castrated and treated with testosterone, this was not due to decreased testosterone levels (which remained unchanged), and could only have been due to the other effects of progesterone. Similar findings have been made for the progestin medroxyprogesterone acetate (MPA) (Michael & Zumpe, 1993; Zumpe et al., 1991; Zumpe & Michael, 1988).
The following excerpt from a review is notable on the topic of progesterone and sexual behavior in primates (Baum, 1983):
The early work of Ball (1941) and of Michael et al. (1968) showed that progesterone acts in the female rhesus monkey to reduce the likelihood of copulation. In contrast to non primate females, no facilitatory action of progesterone on any aspect of feminine sexuality has ever been convincingly demonstrated in primates.
One study in female monkeys found that MPA inhibited sexual behavior while progesterone did not (Pazol et al., 2004). However, MPA is a much more potent progestogen than progesterone, and the progesterone levels were very low (2 ng/mL). Hence, the progesterone levels in this study may have been too low for adequate physiological effect, which might explain the conflicting finding compared to other studies. Another study found increased sexual receptivity in castrated female monkeys treated with a combination of an estrogen and parenteral progesterone (Baum et al., 1977). However, this was relative to a baseline of castration, and the changes may have only been due to the estrogen. Indeed, the same researchers reported decreased sexual receptivity with the addition of progesterone to estrogen in other studies (Baum et al., 1976; Baum et al., 1977).
Mifepristone, a progesterone receptor antagonist, showed no apparent effect on sexual behavior in either female or male monkeys (Nadler et al., 1985).
A notable exception when it comes to progesterone and sexual behavior in animals is female rodents, in which progesterone is stimulatory and induces lordosis (Frye, 2007). Allopregnanolone is involved in the facilitatory effects of progesterone on female sexual behavior in rodents, but has mixed effects, showing either augmentation or inhibition depending on the specifics (King, 2013; Frye, 2007). However, progesterone stimulates sexual behavior in female rodents only acutely, and is actually inhibitory with continuous administration (Pazol et al., 2004; Pazol et al., 2006). Studies in estrogen-primed intact male rats have found that progesterone given systemically does not induce lordosis (Ward et al., 1977). Interestingly however, lordosis was found to be induced in some male rats when progesterone was injected directly into a specific part of the hypothalamus (Ward et al., 1977). The prosexual effects of progesterone in female rodents may be mediated via non-genomic mechanisms, for instance actions of progesterone’s neurosteroid metabolites (Delville, 1991).
In addition to female rodents, research has found that progesterone is involved in normal sexual behavior in male rats (Witt et al., 1995; Andersen & Tufik, 2006). In male rats, castration greatly decreases levels of both testosterone and progesterone and markedly reduces sexual behavior (Witt et al., 1995). Low-dose progesterone administration, resulting in low but physiological male-range levels of progesterone, significantly restores sexual behavior (Witt et al., 1995). Additionally, when testosterone is concomitantly administered, progesterone augments the improvement caused by testosterone and is required for sexual behavior to be fully restored (Witt et al., 1995). The effects are mimicked by progestins like promegestone and blocked by the progesterone receptor antagonist mifepristone, suggesting that they are due specifically to activation of the progesterone receptor (Witt et al., 1995).
However, the findings in male rats probably do not apply to primates. As already described, mifepristone, in contrast to male rats, has no influence on sexual behavior in male monkeys (Nadler et al., 1985). Similarly, a study in castrated male monkeys given testosterone in combination with a relatively low dose of progesterone—resulting in roughly doubled progesterone levels relative to normal male levels—found no difference in sexual behavior compared to castrated male monkeys given testosterone alone (Buhl, Jensen, & Phoenix, 1978). Hence, neither progesterone receptor antagonism nor restoration of progesterone levels following castration seems to influence sexual behavior in male primates. It’s also notable that unlike in male rodents, castration doesn’t appear to reduce progesterone levels in either male monkeys (Zumpe, Clancy, & Michael, 1997) or humans (Waxman et al., 2013). As such, even if the rodent findings did apply to humans, castrated men have normal male-range progesterone levels and would in theory have all the progesterone needed to maintain sexual desire.
The findings on male-range progesterone levels and sexual behavior in male rats are also in contrast to research with higher, supraphysiological levels of progesterone (Hawley & Mosura, 2019). This degree of progesterone exposure has been shown to inhibit sexual behavior in males of most or all species examined, notably including male rats (Hawley & Mosura, 2019). This is the case regardless of influence on testosterone levels (Hawley & Mosura, 2019).
Progesterone levels in women are negatively associated, in some studies strongly, with sexual desire and behavior in women (Shirazi et al., 2019; Roney, 2015; Roney & Simmons, 2013; Roney & Simmons, 2016; Roney, 2019). One conflicting study reported a positive association of luteal-phase progesterone levels with initiation of sexual activity with partners, but the same researchers had contradictory findings in a subsequent study (Holder & Mong, 2017; Roney, 2015; Jones et al., 2019).
Sexual desire is progressively decreased in women during pregnancy, a state characterized by very high levels of estrogens, progesterone, and prolactin (Regan et al., 2003; Gałązka et al., 2014). However, many confounding factors exist (e.g., the other hormonal changes, or being pregnant), and hence causation of the changes can’t necessarily be attributed to progesterone. The observations do suggest that very high levels of an estrogen and progesterone may be unlikely to increase sexual desire however.
A 2013 meta-analysis reported that combined birth control pills, containing both ethinylestradiol and a progestogen, result in either unchanged or increased sexual desire in most women (85%) and decreased sexual desire in a small percentage of women (15%) (Pastor et al., 2013). However, changes in sexual desire seem to be related to the ethinylestradiol component rather than to the progestin component; decreased sexual desire was only associated with birth control pills containing low-dose estrogen (20 μg ethinylestradiol) (Pastor et al., 2013). The fact that combined birth control pills infrequently decrease sexual desire in women is notable because these medications suppress ovulation and hence completely prevent the increase in progesterone levels during the luteal phase. As such, progesterone levels, and by extension circulating levels of allopregnanolone and pregnanolone, remain very low at all times. This suggests little or no importance of the neurosteroid metabolites of progesterone for sexual desire in women.
The fact that combined birth control pills don’t generally affect sexual desire in women is also potentially surprising because total and free testosterone levels are greatly decreased by them due to the ethinylestradiol component (Zimmerman et al., 2014). This is, however, in accordance with accumulating evidence suggesting that physiological levels of androgens in women have little or no involvement in sexual desire (Cappelletti & Wallen, 2016). Rather than progesterone or androgens, what seems to be important for sexual desire in women is estradiol, especially acutely at periovulatory levels (Cappelletti & Wallen, 2016).
A small minority of women treated with depot medroxyprogesterone acetate (DMPA) alone for birth control report decreased libido and only 2.3% cite it as a reason for discontinuation (Schaffir, 2006). A study of 80 women treated with DMPA alone for birth control monitored sexual function and found no difference from baseline to 4 months of therapy (Schaffir, 2006). Findings have been similar for subcutaneous birth control implants with nomegestrol acetate and levonorgestrel (Schaffir, 2006). A randomized controlled trial of 150 women given combined birth control pills, progestin-only birth control pills, and placebo found no difference in sexual desire or activity between progestin-only pills and placebo (Schaffir, 2006).
The addition of a progestin to an estrogen in hormone therapy for menopausal women has been found not to improve sexual desire or function to a greater extent than an estrogen alone in individual studies (Çayan et al., 2008; Myers et al., 1990; Sherwin, 1991; Savolainen-Peltonen et al., 2014; Dennerstein et al., 1980; Alexander et al., 2004; Saadat et al., 2002; Davis et al., 2004; Modelska & Milián, 2004; Sandhu et al., 2011). A couple of studies have found that improvement in sexual desire/function is better with an estrogen alone than with an estrogen plus a progestin, suggesting that progestins might have an adverse influence (Çayan et al., 2008; Dennerstein et al., 1980; Kovalevsky, 2005; Castelo-Branco et al., 2007). Overall however, the available research suggests no change in sexual desire/function with addition of a progestin to an estrogen in menopausal hormone therapy (Sandhu et al., 2011).
Interestingly, a 2018 meta-analysis reported a higher standardized mean difference (SMD) for improvement of sexual desire/function in studies with an estrogen plus a progestogen relative to studies using an estrogen alone (Javadivala et al., 2019). However, there was differing methodology (e.g., sexual measures) and high heterogeneity across studies, as well as a limited number of included studies (particularly of estrogen only). These issues make conclusions on the basis of the differing SMDs problematic. Indeed, the finding is contradicted by individual studies that have included both estrogen only and estrogen plus progestogen groups (see the sources above).
Besides progestogenic activity, it has been suggested that androgenic progestins, like most of the testosterone derivatives, might provide better effects on sexual desire/function than non-androgenic progestins (Graziottin & Serafini, 2011). However, aside from the case of the atypical agent tibolone (Biglia et al., 2010), this has not actually been assessed or shown in any clinical trials (Schaffir, 2006).
A 1975 study published as an abstract with little additional information claimed that some premenopausal women with “frigidity” had high progesterone levels and that treatment with levonorgestrel alone to suppress progesterone levels could increase libido in these women (Kristoffersen & Lebech, 1975). This is very low-quality information however.
Available clinical studies of progesterone and sexual desire in women have observed no changes (Worsley et al., 2016). Neither 200 mg/day oral progesterone nor 10 mg/day oral MPA had any influence on mood or libido in estrogen-treated postmenopausal women in a randomized controlled trial (Saadat et al., 2002). Likewise, treatment of pharmacologically hypogonadal women with 400 mg/day vaginal progesterone suppositories alone did not significantly alter any domain of sexual function in another randomized controlled trial (Schmidt et al., 2009). Treatment of women with subcutaneous implants of progesterone alone for gynecological disorders has been reported to decrease sexual desire in an uncontrolled clinical study (Regan, 1998). Conversely, a retrospective chart review of 137 women with severe premenstrual syndrome treated during the luteal phase with 100–200+ mg/day vaginal progesterone suppositories alone for birth control reported that decreased libido was a side effect in 1 woman (0.7%) (Dalton et al., 1987).
One study assessed the influence on mood and libido of estradiol plus cyclic 200 mg/day oral progesterone in premenopausal women and estradiol plus cyclic 200 mg/day vaginal progesterone in perimenopausal women (Nappi et al., 2004). The premenopausal women were suffering from menstrual irregularities, depression, and sexual dysfunction, while the perimenopausal women were presumably experiencing menopausal symptoms. A significant improvement in libido, sexual arousal, and pain was observed with therapy in the premenopausal women who had a concomitant improvement in anxiety, irritability, and appetite, but not in those who remained depressed. The findings in the perimenopausal women were similar; the hormonal therapy improved sexual desire only in those who experienced improvement in anxiety, panic, and tension, but not in those in whom depression remained. The findings of this study, although interesting, are unfortunately confounded by the lack of an estradiol-only control group, and so can’t necessarily be attributed to progesterone. Moreover, the findings are confounded by the presence and alleviation of the mood symptoms, anxiety, and other problems in the women; it’s possible that estradiol and progesterone did not increase sexual desire themselves but rather it was the improvement of the other symptoms that produced the changes.
Another randomized controlled trial found that an estrogen plus 1.25 mg/day methyltestosterone and 100 mg/day oral progesterone significantly improved sexual desire and function relative to placebo in postmenopausal women (Blümel et al., 2008). However, this study was confounded by the presence of methyltestosterone and the lack of a no-progesterone control group.
Transdermal progesterone cream at a dosage of 32 mg/day had no influence on sexual desire or other parameters in postmenopausal women (Wren et al., 2003; Worsley et al., 2016).
A recent chapter in a book on progestogens included the following passage (Nadjafi-Triebsch, 2015):
Progesterone improves sexual performance in [male] rats . Consequently, progesterone should also improve sexual performance in men due to similarities to human neuro-endocrine mechanisms. Indeed, patients receiving progesterone reported more frequent morning erections and distinctively improved sexual performance.
However, no source or other information (e.g., study design, route/dosage, etc.) was provided. The claim was probably based on clinical experience. In addition, the chapter makes some problematic statements like “progesterone prevents prostate cancer”, “progesterone treats autism”, along with ample reference to low-quality unpublished clinical experience, that seriously hurt its credibility.
High-dose progestogen monotherapy with cyproterone acetate (CPA) or medroxyprogesterone acetate is widely used to suppress sexual desire and function in men with sexual deviance including hypersexuality, paraphilias, and sex offenses (Wiki; Codispoti, 2008). This therapy results in strong sexual suppression and is highly effective for this purpose. Its efficacy is thought to be due to suppression of testosterone levels. However, there is evidence that progestogenic activity in the brain itself and/or increased prolactin levels secondary to progestogenic activity may also be involved (Zumpe, Clancy, & Michael, 1997; Wiki). Although estrogens suppress testosterone levels and increase prolactin levels similarly to progestogens, they are known to have beneficial effects on sexual desire in women, and partly in relation to this, may not result in the same degree of suppression of sexual desire and function as progestogens (Cappelletti & Wallen, 2016; Santoro et al., 2016; Wallen et al., 1984). As with CPA and MPA, progesterone alone by intramuscular injection has been found to substantially suppress sexual desire and function in men (Wiki; Regan, 1998).
Taken together, there appears to be little or no evidence that progesterone or other progestogens improve sexual desire or function in humans. Instead, the available evidence suggests that progestogens are likely to result in either unchanged or decreased sexual desire and function. Decreased sexual desire/function may be especially likely at high doses. In any case, more research on progestogens and sexual desire, particularly with non-oral progesterone, is warranted.