The impact of transdermal testosterone treatment on quality of life in women with diminished ovarian reserve: secondary analysis of a randomized controlled trial

STUDY QUESTION: Does transdermal testosterone treatment improve fertility-related quality of life (QOL) in women with diminished ovarian reserve (DOR)?

SUMMARY ANSWER: Transdermal testosterone for 9 weeks at a dose of 5.5 mg per day did not result in improved fertility-related QOL compared with placebo in women with DOR.

WHAT IS KNOWN ALREADY: Reduced QOL is prevalent in women with infertility, many of whom have DOR. Several studies have shown a correlation between DOR and lower testosterone levels, and testosterone is frequently prescribed to women with DOR undergoing fertility treatment. Some studies have reported that testosterone therapy may improve wellbeing in pre- and post-menopausal women, though others have found no benefit. There are no studies evaluating the effect of testosterone on QOL in women undergoing fertility treatment.

STUDY DESIGN, SIZE, DURATION: Pre-planned secondary analysis of a double-blind placebo-controlled randomized controlled trial that included 288 participants recruited between April 2015 and August 2022. Of these, 213 completed QOL surveys both before and after treatment and were eligible for inclusion in this analysis.

PARTICIPANTS/MATERIALS, SETTINGS, METHODS: Participants were women aged 18-43 years with DOR according to the Bologna criteria and planning to undergo IVF treatment at one of eight fertility clinics in Spain, Belgium, and Denmark. Participants were randomized to 5.5 mg of transdermal testosterone per day as 1% gel (n = 106) or an identical placebo (n = 107), applied for a median of 60 days prior to commencing ovarian stimulation. QOL was assessed using the FertiQoL instrument prior to commencing the intervention, and at the completion of the intervention but prior to commencing ovarian stimulation. QOL scores were compared using a one-way ANCOVA adjusted for age, BMI, parity, history of IVF treatment, and baseline FertiQoL scores.

MAIN RESULTS AND THE ROLE OF CHANCE: There were no significant differences in baseline characteristics between the testosterone (n = 106) and placebo (n = 107) groups. After adjustment, testosterone showed no benefit over placebo for the Total FertiQoL score (F(1,204)=0.07, P = 0.79), the Core and Treatment scores, nor for any of the included FertiQoL subscales. Total testosterone levels were higher in the testosterone group than the placebo group at the end of the treatment (3.2 ± 2.7 nmol/l vs 0.6 ± 0.4 nmol/l, P < 0.001).

LIMITATION, REASONS FOR CAUTION: QOL was a secondary outcome in this trial, and participants were not recruited based on a low QOL.

WIDER IMPLICATIONS OF THE FINDINGS: Considering the available evidence, including the current study, premenopausal women are unlikely to benefit from testosterone treatment with regard to wellbeing and QOL. This study provides further evidence that testosterone should not be seen as a treatment for low wellbeing or QOL.

STUDY FUNDING/COMPETING INTEREST(S): The study was supported by unrestricted grants and support from Besins Healthcare, Roche Diagnostics, and Ferring Pharmaceuticals. The study medication and placebo were provided by Besins Healthcare. Funders had no access to patient data and had no role in the interpretation of the data, nor in the writing or approval of the final manuscript. The researchers were independent of the funders and had full access to all the data in the study. S.J.L. has received honoraria from Merck, Organon, and Hologic, consulting fees from Merck, and travel support from Merck, Organon, Besins Healthcare, and Ferring Pharmaceuticals. S.R.D. has received grants from NHMRC Australia, MS Australia, MRFF Australia, the Australian Heart Foundation, and Lawley Pharmaceuticals, consulting fees from Besins Healthcare, Astellas, and Abbott, honoraria from Theramex, Astellas, and Bayer, travel support from Astellas, and drugs/placebo from Lawley Pharmaceuticals for clinical trials; she is an Executive Board Member of the Australian Academy of Health and Medical Sciences. C.B. has received honoraria from Ferring Pharmaceuticals, IBSA, Organon, Merck A/S, and Abbott. A.G. has received honoraria from Lab Seid and travel support from Merck Serono. P.H. has received honoraria from Merck, IBSA, Gedeon Richter, and Besins Healthcare. L.D.L.F. has received consulting fees from Gedeon Richter, Ferring Pharmaceuticals, and Organon, travel support (personal and to institution) from Gedeon Richter, Ferring Pharmaceuticals, IBSA, Merck, Organon, and Theramex, and educational support (to institution) from Gedeon Richter and Merck. A.P. has received grants from Gedeon Richter, Ferring Pharmaceuticals, and Merck A/S, consulting fees from Gedeon Richter and Ferring Pharmaceuticals, honoraria from Ferring Pharmaceuticals, Gedeon Richter, Merck A/S, Abbott, and Organon, and travel support from Gedeon Richter. D.S. has received grants from Organon, Ferring Pharmaceuticals, Besins Healthcare, Gedeon Richter, and Vitrolife, honoraria from Organon, Ferring Pharmaceuticals, Besins Healthcare, Gedeon Richter, and Merck, travel support from Organon, Ferring Pharmaceuticals, Besins Healthcare, Gedeon Richter, and Merck, and is President of the Belgian Society for Reproductive Medicine. N.P.P. has received grants from Merck Serono, Ferring Pharmaceuticals, Theramex, Organon, Besins Healthcare, and Gedeon Richter, consulting fees from Merck Serono, Besins Healthcare, Organon, IBSA, FertilAI, and Alife, and honoraria from Merck Serono, Theramex, IBSA, Ferring Pharmaceuticals, Organon, Roche Diagnostics, and Besins Healthcare. S.G.M., F.M., and F.F. have no interests to declare.

TRIAL REGISTRATION NUMBER: NCT02418572 (ClinicalTrials.gov).