Abstract
Purpose
To investigate the effects of dehydroepiandrosterone (DHEA) supplementation on female sexual function in premenopausal infertile women of advanced ages.
Methods
This observational study was conducted in an academically affiliated private fertility center. Patients included 87 premenopausal infertile women, 50 of whom completed the study including the Female Sexual Function Index (FSFI) questionnaires and comprehensive endocrine evaluation before and 4–8 weeks after initiating 25 mg of oral micronized DHEA TID.
Results
Age of patients was 41.1 ± 4.2 years, BMI 24.4 ± 6.1 kg/m2, 86% were married, and 42% were parous. Following supplementation with DHEA, all serum androgen levels increased (each P < 0.0001), while FSH levels decreased by 2.6 ± 4.4 from a baseline of 10.3 ± 5.4 mIU/mL (P = 0.009). The FSFI score for the whole study group increased by 7% (from 27.2 ± 6.9 to 29.2 ± 5.6; P = 0.0166). Domain scores for desire increased by 17% (P = 0.0004) and by 12% for arousal (P = 0.0122); lubrication demonstrated an 8% trend towards improvement (P = 0.0551), while no changes in domain scores for orgasm, satisfaction, or pain were observed. Women in the lowest starting FSFI score quartile (<25.7), experienced a 6.1 ± 8.0 (34%) increase in total FSFI score following DHEA supplementation. Among these women, improvements in domain categories were noted for desire (40%), arousal (46%), lubrication (33%), orgasm (54%), satisfaction (24%), and pain (25%).
Conclusions
This uncontrolled observational study implies that supplementation with DHEA improves sexual function in older premenopausal women with low baseline FSFI scores.
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References
M.E. McCool, A. Zuelke, M.A. Theurich, H. Knuettel, C. Ricci, C. Apfelbacher, Prevalence of female sexual dysfunction among premenopausal women: a systematic review and meta-analysis of observational studies. Sex. Med. Rev. 4, 197–212 (2016)
J.M. Weinberger, J. Houman, A.T. Caron, J. Anger, Female sexual dysfunction: a systematic review of outcomes across various treatment modalities. Sex Med Rev. 2018 Feb 3. pii: S2050-0521(18)30001-5. https://doi.org/10.1016/j.sxmr.2017.12.004
H.V. Joffe, C. Chang, C. Sewell, O. Easley, C. Nguyen, S. Dunn, K. Lehrfeld, L. Lee, M.J. Kim, A.F. Slagle, J. Beitz, FDA approval of flibanserin—treating hypoactive sexual desire disorder. N. Engl. J. Med. 374, 101–104 (2016)
R. Basson, J. Berman, A. Burnett, L. Derogatis, D. Ferguson, J. Fourcroy, I. Goldstein, A. Graziottin, J. Heiman, E. Laan, S. Leiblum, H. Padma-Nathan, R. Rosen, K. Segraves, R.T. Segraves, R. Shabsigh, M. Sipski, G. Wagner, B. Whipple, Report of the international consensus development conference on female sexual dysfunction: definitions and classifications. J. Urol. 163, 888–893 (2000)
A.T. Guay, J. Jacobson, Decreased free testosterone and dehydroepiandrosterone-sulfate (DHEA-S) levels in women with decreased libido. J. Sex Marital Ther. 28(Suppl 1), 129–142 (2002)
B. Turna, E. Apaydin, B. Semerci, B. Altay, N. Cikili, O. Nazli, Women with low libido: correlation of decreased androgen levels with female sexual function index. Int. J. Impot. Res. 17, 148–153 (2005)
R.E. Nappi, To be or not to be in sexual desire: the androgen dilemma. Climacteric 18, 672–674 (2015)
R. Worsley, R.J. Bell, P. Gartoulla, S.R. Davis, Prevalence and predictors of low sexual desire, sexually related personal distress, and hypoactive sexual desire dysfunction in a community-based sample of midlife women. J. Sex. Med. 14, 675–686 (2017)
M.M. Kushnir, T. Blamires, A.L. Rockwood, W.L. Roberts, B. Yue, E. Erdogan, A.M. Bunker, A.W. Meikle, Liquid chromatography-tandem mass spectrometry assay for androstenedione, dehydroepiandrosterone, and testosterone with pediatric and adult reference intervals. Clin. Chem. 56, 1138–1147 (2010)
N. Orentreich, J.L. Brind, R.L. Rizer, J.H. Vogelman, Age changes and sex differences in serum dehydroepiandrosterone sulfate concentrations throughout adulthood. J. Clin. Endocrinol. Metab. 59, 551–555 (1984)
N. Gleicher, A. Kim, A. Weghofer, V.A. Kushnir, A. Shohat-Tal, E. Lazzaroni, H.J. Lee, D.H. Barad, Hypoandrogenism in association with diminished functional ovarian reserve. Hum. Reprod. 28, 1084–1091 (2013)
N. Gleicher, V.A. Kushnir, A. Weghofer, D.H. Barad, The importance of adrenal hypoandrogenism in infertile women with low functional ovarian reserve: a case study of associated adrenal insufficiency. Reprod. Biol. Endocrinol. 14, 23 (2016)
P.J. Robinson, R.J. Bell, M.K. Christakis, S.R. Ivezic, S.R. Davis, Aromatase inhibitors are associated with low sexual desire causing distress and fecal incontinence in women: an observational study. J. Sex. Med. 14, 1566–1574 (2017)
S.R. Davis, R. Worsley, K.K. Miller, S.J. Parish, N. Santoro, Androgens and female sexual function and dysfunction—findings from the Fourth International Consultation of Sexual Medicine. J. Sex. Med. 13, 168–178 (2016)
M. Khera, Testosterone therapy for female sexual dysfunction. Sex. Med. Rev. 3, 137–144 (2015)
M. Panjari, S.R. Davis, DHEA therapy for women: effect on sexual function and wellbeing. Hum. Reprod. Update 13, 239–248 (2007)
R.F. Spark, Dehydroepiandrosterone: a springboard hormone for female sexuality. Fertil. Steril. 77(Suppl 4), S19–S25 (2002)
C.S. Scheffers, S. Armstrong, A.E. Cantineau, C. Farquhar, V. Jordan, Dehydroepiandrosterone for women in the peri- or postmenopausal phase. Cochrane Database Syst. Rev. 1, CD011066 (2015)
W. Arlt, F. Callies, J.C. van Vlijmen, I. Koehler, M. Reincke, M. Bidlingmaier, D. Huebler, M. Oettel, M. Ernst, H.M. Schulte, B. Allolio, Dehydroepiandrosterone replacement in women with adrenal insufficiency. N. Engl. J. Med. 341, 1013–1020 (1999)
F. Labrie, D.F. Archer, W. Koltun, A. Vachon, D. Young, L. Frenette, D. Portman, M. Montesino, I. Côté, J. Parent, L. Lavoie, A. Beauregard, C. Martel, M. Vaillancourt, J. Balser, É. Moyneur; VVA Prasterone Research Group, Efficacy of intravaginal dehydroepiandrosterone (DHEA) on moderate to severe dyspareunia and vaginal dryness, symptoms of vulvovaginal atrophy, and of the genitourinary syndrome of menopause. Menopause 23, 243–256 (2016)
N. Gleicher, D.H. Barad, Dehydroepiandrosterone (DHEA) supplementation in diminished ovarian reserve (DOR). Reprod. Biol. Endocrinol. 9, 67 (2011)
N. Gleicher, A. Kim, A. Weghofer, A. Shohat-Tal, E. Lazzaroni, H.J. Lee, D.H. Barad, Starting and resulting testosterone levels after androgen supplementation determine at all ages in vitro fertilization (IVF) pregnancy rates in women with diminished ovarian reserve (DOR). J. Assist. Reprod. Genet. 30, 49–62 (2013)
N. Gleicher, A. Weghofer, D.H. Barad, Improvement in diminished ovarian reserve after dehydroepiandrosterone supplementation. Reprod. Biomed. Online 21, 360–365 (2010)
D. Barad, H. Brill, N. Gleicher, Update on the use of dehydroepiandrosterone supplementation among women with diminished ovarian function. J. Assist. Reprod. Genet. 24, 629–634 (2007)
A. Sen, S.R. Hammes, Granulosa cell-specific androgen receptors are critical regulators of ovarian development and function. Mol. Endocrinol. 24, 1393–1403 (2010)
A. Sen, H. Prizant, A. Light, A. Biswas, E. Hayes, H.J. Lee, D. Barad, N. Gleicher, S.R. Hammes, Androgens regulate ovarian follicular development by increasing follicle stimulating hormone receptor and microRNA-125b expression. Proc. Natl. Acad. Sci. U.S.A. 111, 3008–3013 (2014)
L.T. Lin, P.H. Wang, S.N. Chen, C.J. Li, Z.H. Wen, J.T. Cheng, K.H. Tsui, Protection of cumulus cells following dehydroepiandrosterone supplementation. Gynecol. Endocrinol. 33, 100–104 (2017)
H. Prizant, N. Gleicher, A. Sen, Androgen actions in the ovary: balance is key. J. Endocrinol. 222, R141–R151 (2014)
C.R. Mendonça, J.T. Arruda, M. Noll, P.M.O. Campoli, W.N.D. Amaral, Sexual dysfunction in infertile women: a systematic review and meta-analysis. Eur. J. Obstet. Gynecol. Reprod. Biol. 215, 153–163 (2017)
L.S. Millheiser, A.E. Helmer, R.B. Quintero, L.M. Westphal, A.A. Milki, R.B. Lathi, Is infertility a risk factor for female sexual dysfunction? A case-control study. Fertil. Steril. 94, 2022–2025 (2010)
R. Rosen, C. Brown, J. Heiman, S. Leiblum, C. Meston, R. Shabsigh, D. Ferguson, R. D’Agostino, The Female Sexual Function Index (FSFI): a multidimensional self-report instrument for the assessment of female sexual function. J. Sex Marital Ther. 26, 191–208 (2000)
A. Shohat-Tal, A. Sen, D.H. Barad, V. Kushnir, N. Gleicher, Genetics of androgen metabolism in women with infertility and hypoandrogenism. Nat. Rev. Endocrinol. 11, 429–441 (2015)
N. Gleicher, K. Seier, V.A. Kushnir, A. Weghofer, Y.G. Wu, Q. Wang, D.F. Albertini, D.H. Barad, Associations between peripheral androgens and cortisol in infertile women. J Steroid Biochem Mol Biol. 2016 Apr;158, 82-89
M. Stomati, P. Monteleone, E. Casarosa, B. Quirici, S. Puccetti, F. Bernardi, A.D. Genazzani, L. Rovati, M. Luisi, A.R. Genazzani, Six-month oral dehydroepiandrosterone supplementation in early and late postmenopause. Gynecol. Endocrinol. 14, 342–363 (2000)
J.M. Weinberger, J. Houman, A.T. Caron, D.N. Patel, A.S. Baskin, A.L. Ackerman, K.S. Eilber, J.T. Anger, Female sexual dysfunction and the placebo effect: a meta-analysis. Obstet. Gynecol. 132(2), 453–458 (2018)
J.L. Shifren, B.U. Monz, P.A. Russo, A. Segreti, C.B. Johannes, Sexual problems and distress in United States women: prevalence and correlates. Obstet. Gynecol. 112, 970–978 (2008)
Funding
This work was supported by the Foundation for Reproductive Medicine and intramural funds of the Center for Human Reproduction.
Author contributions
V.A.K., D.H.B., and N.G. developed the concept of the study; all authors contributed to data accumulation. S.K.D., A.W., and V.A.K. contributed to data analysis; all authors contributed to data interpretation. V.A.K. wrote the manuscript. All authors contributed to revisions of the manuscript and approved the final submission. V.A.K. had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
Availability of data and material
Anonymized patient level data are accessible by contacting Mrs. Jolanta Tapper at jtapper@thechr.com.
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Conflict of interest
N.G. and D.H.B. are co-inventors on several pending and already awarded U.S. patents claiming fertility benefits from androgen supplementation in women with low functional ovarian reserve (LFOR). Both receive royalties from Fertility Nutraceuticals, LLC, in which N.G. also holds shares. Other authors declare that they have no conflict of interest.
Ethics approval
This study received Institutional Review Board (IRB) approval (ER11052015-01) on 11/11/2015 from the IRB of the Center for Human Reproduction. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
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Informed consent was obtained from all individual participants included in the study.
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Kushnir, V.A., Darmon, S.K., Barad, D.H. et al. Effects of dehydroepiandrosterone (DHEA) supplementation on sexual function in premenopausal infertile women. Endocrine 63, 632–638 (2019). https://doi.org/10.1007/s12020-018-1781-3
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DOI: https://doi.org/10.1007/s12020-018-1781-3