Has testosterone passed the test in premenopausal women with low libido? A systematic review

Figures & data

Figure 1 Comparison of the old and new classifications for female sexual dysfunction.

Table 1 Studies that examined serum testosterone levels and sexual desire

Authors	Study population	Testosterone serum levels	Findings
Wåhlin-Jacobsen et al^Citation23	560 women (included premenopausal and postmenopausal women) Exclusion criteria: pregnancy, nursing, postpartum, thyroid disease, pituitary disease, PCOS, cancer, use of antidepressants or antipsychotics	Means not given	No correlation between total testosterone and sexual desire in the cohort A statistically significant correlation was found between sexual desire and free testosterone in the cohort. However, on subanalysis, this correlation persisted only in women aged 19–24 years. The correlation did not persist in women aged 25–65 years
Basson et al^Citation24	245 women (included premenopausal and postmenopausal women) Exclusion criteria: depression, abnormal body mass index, current use of sex hormones or medications known to affect libido, medical conditions known to inhibit sexual function, dyspareunia, substance abuse, smoking, severe relationship discord, lack of English fluency	Control group: Total testosterone: 21 ng/dL (±0.1 SD) Sexual dysfunction group (generalized sexual desire and arousal disorders): Total testosterone: 19 ng/dL (±0.11 SD)	No differences in testosterone levels between women with sexual dysfunction and controls
Alder et al^Citation25	29 premenopausal women with Stage I or II breast cancer Exclusion criteria: major psychiatric disorders, cardiovascular, metabolic, or neurological disease	Chemotherapy group: Total testosterone: 14 ng/dL (±0.05 SD) No chemotherapy group: Total testosterone: 13 ng/dL (±0.07 SD)	Testosterone levels did not predict sexual dysfunction
Elaut et al^Citation30	92 women (62 transsexual [castrated male to female] women and 30 ovulating women) Exclusion criteria: use of steroidal contraception, use of medication that could influence androgen levels or sexual desire, alcoholism, cirrhosis, Cushing syndrome, hyper and hypothyroidism	Transsexual women: Total testosterone: 20 ng/dL (±9.6 SD) Free testosterone: 0.26 ng/dL (±0.16 SD) Ovulating women: Total testosterone: 33.9 ng/dL (±17.9 SD) Free testosterone: 0.5 ng/dL (±0.31 SD)	Transsexual women had lower free and total testosterone, but these levels did not correlate with a higher risk for HSDD Ovulating women demonstrated a correlation between free and total testosterone and solitary sexual desire. However, the correlation did not hold true for dyadic sexual desire Reference ranges provided in this study: Total testosterone: 10–80 ng/dL Free testosterone: 0.2–0.5 ng/dL
Turna et al^Citation31	40 premenopausal women, 40 postmenopausal women Among each group, half had decreased sexual desire and the other half were controls Exclusion criteria: adrenal insufficiency, thyroid disease, depression, chronic fatigue syndrome, chronic metabolic disease, radiotherapy, and chemotherapy	Overall mean serum values not reported	Decreased free testosterone and total testosterone were correlated with lower female sexual function indexes. However, all mean serum levels reported were considered to be within the reference range; however, the reference range used was not reported
Riley^Citation26	30 women (15 controls and 15 with sexual drive disorder) Exclusion criteria: genital atrophy or infection, sexual aversion, depression, and psychiatric disturbance. Use of medications that impair sexual function or disrupt hormonal control, drug abuse, alcohol abuse, smoking, pregnancy, recent childbirth, abnormal menses, and thyroid dysfunction	Low libido: Total testosterone: 47 ng/dL Controls: Total testosterone: 60.5 ng/dL (no statistical difference) Low libido: Free testosterone index: 2.27% Controls: Free testosterone index: 3.92% (P=0.02)	Women with lifelong absence of sexual drive had significantly lower levels of free testosterone index Free testosterone index did not correlate with the index of sexual desire The total testosterone levels were not different The authors reported that there were no testosterone levels below the reference range Reference range reported in this study: Total testosterone: 14–101 ng/dL
Santoro et al^Citation32	2,961 premenopausal women aged 42–52 years Exclusion criteria: could not have taken any hormones for at least 3 months prior to enrollment	Total testosterone: Median: 41 ng/dL	Authors reported that “Sexual desire was, at best, marginally related to circulating testosterone levels”
Davis et al^Citation27	1,021 women, aged 18–75 years. Exclusion criteria: pregnancy, postpartum, acute psychiatric illness, major illness, gynecological surgery, cancer, potentially confounding conditions, or medications	Not given	Authors reported that “The ROC curves provided no evidence for total or free testosterone being useful for discriminating between individuals with or without low sexual function”
Nyunt et al^Citation18	41 premenopausal women (29 with low libido and 12 controls), aged 18–45 years Specific exclusion criteria not given	Total testosterone: Low libido group: 28 ng/dL (±0.38 SD) Controls: 28 ng/dL (±0.41 SD) Free testosterone: Low libido group: 0.002 ng/dL (±0.02 SD) Controls: 0.002 ng/dL (±0.01 SD)	No difference in testosterone or free testosterone levels between subjects and controls
Glaser et al^Citation29	108 premenopausal women, 192 postmenopausal women Exclusion criteria: breast cancer	Values not given	Authors conclude “Our results showed that a single serum measurement of testosterone was not useful in the diagnosis of androgen deficiency. Neither the incidence/severity of symptoms nor treatment effect correlated with baseline free or total testosterone levels, consistent with previous studies”

Abbreviations: HSDD, hypoactive sexual desire disorder; PCOS, polycystic ovarian syndrome; SD, standard deviation.

Table 2 Testosterone treatment in premenopausal females

Authors	Study population	Treatment	Results	Testosterone serum levels	Androgenic side effects	Comments
Davis et al^Citation33	261 premenopausal women with a low sexuality score Exclusion criteria: planning a pregnancy, pregnant, or breastfeeding. Relationship problems, dyspareunia, on medication known to interfere with normal sexual function, history of androgen therapy. Hirsutism, acne, cancer, major illness, genital bleeding, heavy alcohol use, drug addiction. 16-week treatment	Placebo Low-dose transdermal testosterone spray Medium-dose transdermal testosterone spray High-dose testosterone spray	No change in SSE in low or high dose when compared to placebo The intermediate dose had an increase in SSEs, 2.48 versus 1.7 in placebo	Placebo: Total testosterone 24.2 ng/dL (±0.25 SD) Low dose: Total testosterone 42.4 ng/dL (±0.87 SD) Intermediate dose: Total testosterone 36.9 ng/dL (±0.46 SD) High dose: Total testosterone 56.8 ng/dL (±0.88 SD)	81%–86% of the treatment groups report side effects Hypertrichosis 0% in placebo group 15.2%–28.4% in the treatment groups Acne 4.7% in placebo group 7.6%–9% in treatment groups	The only group that had a statistically significant difference was the intermediate group (increase in SSEs, 2.48 vs 1.7 in placebo). However, the testosterone serum level in the intermediate group was actually lower than the serum level in the low- or high-dose groups
Goldstat et al^Citation34	34 premenopausal women with diminished sexuality Exclusion criteria: planning pregnancy, relationship problems, dyspareunia, taking medication known to affect sexual function, recent androgen treatment, acne, hirsutism, cancer, thromboembolic disease, major illness or disease, and heavy alcohol use 12-week treatment	Placebo Testosterone cream	Improvement in sexuality score (15.7 points)	Placebo: Total testosterone 31.4 ng/dL (±0.44 SD) Treatment: Total testosterone 74.4 ng/dL (±2.58 SD)	None	While there was a statistically significant increase in the Sabbatsberg Sexual Self-Rating Scale with treatment, there was no statistically significant increase in the testosterone serum level when compared to placebo Reference range reported in this study: Total testosterone 14–78 ng/dL
Chudakov et al^Citation35	Ten premenopausal women with HSDD Exclusion criteria: psychiatric disorders 4-week treatment	Placebo Testosterone gel	Increase in ease of arousal in testosterone gel group vs placebo (4.0 vs 4.4) No change in desire	Not given	One report of slight increase of hirsutism	Did not increase libido
Glaseret al^Citation29	108 premenopausal women, 192 postmenopausal women with suspected androgen deficiency Exclusion criteria: breast cancer 12-week treatment	Testosterone pellet (dose varied according to body weight and investigator judgment) No control group	Increased urogenital subgroup score on the MRS noted after treatment. Score went from severe to mild (4.9 to 1.3). The urogenital subgroup scale evaluates sexual problems, bladder problems, and vaginal dryness	Not studied	Authors report that some women reported a slight increase in facial hair, but they did specify how many women. 4.4% of women had increased irritability	While an improvement in the urogenital subgroup score was noted, the sexual problem score improvement in premenopausal women was not reported or discussed

Abbreviations: HSDD, hypoactive sexual desire disorder; MRS, menopausal rating scale; SD, standard deviation; SSE, sexually satisfying event.

Wåhlin-JacobsenSPedersenAnette TønnWåhlin-JacobsenSIs there a correlation between androgens and sexual desire in women?J Sex Med201512235837325475395

 PubMed Web of Science ®Google Scholar

BassonRBrottoLAPetkauAJLabrieFRole of androgens in women’s sexual dysfunctionMenopause201017596297120539247

 PubMed Web of Science ®Google Scholar

AlderJZanettiRWightEUrechCFinkNBitzerJSexual dysfunction after premenopausal stage I and II breast cancer: do androgens play a role?J Sex Med2008581898190618554258

 PubMed Web of Science ®Google Scholar

ElautEDe CuypereGDe SutterPHypoactive sexual desire in transsexual women: prevalence and association with testosterone levelsEur J Endocrinol2008158339339918299474

 PubMed Web of Science ®Google Scholar

TurnaBApaydinESemerciBAltayBCikiliNNazliOWomen with low libido: correlation of decreased androgen levels with female sexual function indexInt J Impot Res200517214815315592425

 PubMed Web of Science ®Google Scholar

RileyAControlled studies on women presen ting with sexual drive disorder: I endocrine statusJ Sex Marital Ther200026326928310929575

 PubMed Web of Science ®Google Scholar

SantoroNTorrensJCrawfordSCorrelates of circulating androgens in mid-life women: the study of women’s health across the nationJ Clin Endocrinol Metab20059084836484515840738

 PubMed Web of Science ®Google Scholar

DavisSRDavisonSLDonathSBellRCirculating androgen levels and self-reported sexual function in womenJAMA20052941919615998895

 PubMed Web of Science ®Google Scholar

NyuntAStephenGGibbinJAndrogen status in healthy premenopausal women with loss of libidoJ Sex Marital Ther20103117380

 Web of Science ®Google Scholar

GlaserRYorkAEDimitrakakisCBeneficial effects of testosterone therapy in women measured by the validated Menopause Rating Scale (MRS)Maturitas201168435536121177051

 PubMed Web of Science ®Google Scholar

DavisSPapaliaMANormanRJSafety and efficacy of a testosterone metered-dose transdermal spray for treating decreased sexual satisfaction in premenopausal womenAnnu Intern Med2008148569577

 PubMed Web of Science ®Google Scholar

GoldstatRBrigantiETranJWolfeRDavisSRTransdermal testosterone therapy improves well-being, mood, and sexual function in premenopausal womenMenopause200310539039814501599

 PubMed Web of Science ®Google Scholar

ChudakovBBen ZionIZBelmakerRHTransdermal testosterone gel PRN application for hypoactive sexual desire disorder in premenopausal women: a controlled pilot study of the effects on the arizona sexual experiences scale for females and sexual function questionnaireJ Sex Med20074120420817233786

 PubMed Web of Science ®Google Scholar