10,606
Views
4
CrossRef citations to date
0
Altmetric
Society Report

International Society for the Study of Women's Sexual Health Clinical Practice Guideline for the Use of Systemic Testosterone for Hypoactive Sexual Desire Disorder in Women

, MD, , MD, , MBBS, PhD, , MD, PhD, , MD, , BA, CSE, , PhD, , PhD, , MD, , MD, PhD, , MD, PhD, , MD, , PhD & , MD show all
Pages 533-550 | Received 02 Jul 2020, Accepted 19 Oct 2020, Published online: 01 Apr 2021

References

  • Abdallah R, Simon JA. Testosterone therapy in women: its role in the management of hypoactive sexual desire disorder. Int J Impot Res. 2007;19:458–463.
  • Hubayter Z, Simon JA. Testosterone therapy for sexual dysfunction in postmenopausal women. Climacteric. 2008;11:181–191.
  • Krapf J, Simon JA. The role of testosterone in the management of hypoactive sexual desire disorder in postmenopausal women. Maturitas. 2009;63:213–219.
  • Davis S, Wahlin-Jacobsen S. Testosterone in women – the clinical significance. Lancet Diabetes Endocrinol. 2015;3:980–992.
  • Islam RM, Bell RJ, Green S, et al. Safety and efficacy of testosterone for women: a systematic review and meta-analysis of randomised controlled trial data. Lancet Diabetes Endocrinol. 2019;7:754–766.
  • Davis SR, Baber R, Panay N, et al. Global consensus position statement on the use of testosterone therapy for women. J Sex Med. 2019;16:1331–1337.
  • Davis SR, Baber R, Panay N, et al. Global consensus position statement on the use of testosterone therapy for women. Climacteric. 2019;22:429–434.
  • Davis SR, Baber R, Panay N, et al. Global consensus position statement on the use of testosterone therapy for women. J Clin Endocrinol Metab. 2019;104:4660–4666.
  • Davis SR, Baber R, Panay N, et al. Global consensus position statement on the use of testosterone therapy for women. Maturitas. 2019;128:89–93.
  • Simon JA, Kapner MD. The saga of testosterone for menopausal women at the Food and Drug Administration (FDA). J Sex Med. 2020;17:826–829.
  • Braunstein G, Sundwall DA, Katz M, et al. Safety and efficacy of a testosterone patch for the treatment of hypoactive sexual desire disorder in surgically menopausal women: a randomized, placebo-controlled trial. Arch Intern Med. 2005;165:1582–1589.
  • Simon J, Braunstein G, Nachtigall L, et al. Testosterone patch increases sexual activity and desire in surgically menopausal women with hypoactive sexual desire disorder. J Clin Endocrinol Metab. 2005;90:5226–5233.
  • Rossouw J, Anderson GL, Prentice RL, et al. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the women's health initiative randomized controlled trial. JAMA. 2002;288:321–333.
  • Anderson GL, Limacher M, Assaf AR, et al. Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: the women's health initiative randomized controlled trial. JAMA. 2004;291:1701–1712.
  • Clayton A, Goldstein I, Kim NN, et al. The International Society for the Study of Women's Sexual Health process of care for management of hypoactive sexual desire disorder in women. Mayo Clin Proc. 2018;93:467–487.
  • American Psychiatric Association. Diagnostic and statistical manual of mental disorders IV, text revision (DSM-IV-TR). Washington DC: American Psychiatric Association; 2003.
  • American Psychological Association. Diagnostic and statistical manual of mental disorders. 5th ed. DSM-5. Arlington (VA): American Psychological Association; 2013.
  • Parish SJ, Goldstein AT, Goldstein SW, et al. Toward a more evidence-based nosology and nomenclature for female sexual dysfunctions-part II. J Sex Med. 2016;13:1888–1906.
  • McCabe M, Sharlip ID, Atalla E, et al. Definitions of sexual dysfunctions in women and men: a consensus statement from the fourth international consultation on sexual medicine 2015. J Sex Med. 2016;13:135–143.
  • World Health Organization. The ICD-10 classification of mental and behavioural disorders: clinical descriptions and diagnostic guidelines. World Heath Organization. [cited 2020 Jan 25]. Available from: https://apps.who.int/iris/handle/10665/37958.
  • Reed GM, Drescher J, Krueger RB, et al. Disorders related to sexuality and gender identity in the ICD-11: revising the ICD-10 classification based on current scientific evidence, best clinical practices, and human rights considerations. World Psychiatry. 2016;15:205–221.
  • Derogatis LR, Clayton A, Rosen R, et al. Do multiple convergent measures of female sexual dysfunction (FSD) support sexual desire and arousal disorders as distinct diagnoses? J Sex Med. 2010;7:S142.
  • Clayton A, DeRogatis IR, Rosen R, et al. Do clinical research data support sexual desire and arousal disorders as distinct diagnoses? J Sex Med. 2011;7:S143.
  • Simon JA, Davis SR, Althof SE, et al. Sexual well-being after menopause: an International Menopause Society white paper. Climacteric. 2018;21:415–427.
  • Shifren J, Monz BU, Russo PA, et al. Sexual problems and distress in United States women: prevalence and correlates. Obstet Gynecol. 2008;112:970–978.
  • Nicolosi A, Glasser DB, Kim SC, et al. Sexual behaviour and dysfunction and help-seeking patterns in adults aged 40-80 years in the urban population of Asian countries. BJU Int. 2005;95:609–614.
  • Hayes RD, Dennerstein L, Bennett CM, et al. Relationship between hypoactive sexual desire disorder and aging. Fertil Steril. 2007;87:107–112.
  • Worsley R, Bell RJ, Gartoulla P, et al. 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. 2017;14:675–686.
  • Zeleke B, Bell RJ, Billah B, et al. Hypoactive sexual desire dysfunction in community-dwelling older women menopause. Menopause. 2017;24:391–399.
  • Hill K. The demography of menopause. Maturitas. 1996;23:113–127.
  • Maclaran K, Panay N. Current concepts in premature ovarian insufficiency. Womens Health (Lond). 2015;11:169–182.
  • Kingsberg SA, Larkin LC, Liu JH. Clinical effects of early or surgical menopause. Obstet Gynecol. 2020;135:853–868.
  • Luborsky JL, Meyer P, Sowers MF, et al. Premature menopause in a multi-ethnic population study of the menopause transition. Hum Reprod. 2003;18:199–206.
  • Soman M, Huang LC, Cai WH, et al. Serum androgen profiles in women with premature ovarian insufficiency: a systematic review and meta-analysis. Menopause. 2019;26:78–93.
  • Judd HL, Judd GE, Lucas WE, et al. Endocrine function of the postmenopausal ovary: concentration of androgens and estrogens in ovarian and peripheral vein blood. J Clin Endocrinol Metab. 1974;39:1020–1024.
  • Shuster LT, Rhodes DJ, Gostout BS, et al. Premature menopause or early menopause: long-term health consequences. Maturitas. 2010;65:161–166.
  • Santoro N. Mechanisms of premature ovarian failure. Ann Endocrinol (Paris). 2003;64:87–92.
  • Mahal AS, Rhoads KF, Elliott CS, et al. Inappropriate oophorectomy at time of benign premenopausal hysterectomy. Menopause. 2017;24:947–953.
  • Moore B, Steiner CA, David PH, et al. Trends in hysterectomies and oophorectomies in hospital inpatient and ambulatory settings, 2005–2013. Statistical Brief #214 (November). Rockville (MD): Agency for Healthcare Research and Quality; 2016.
  • Novetsky AP, Boyd LR, Curtin JP. Trends in bilateral oophorectomy at the time of hysterectomy for benign disease. Obstet Gynecol. 2011;118:1280–1286.
  • Sarrel PM, Sullivan SD, Nelson LM. Hormone replacement therapy in young women with surgical primary ovarian insufficiency. Fertil Steril. 2016;106:1580–1587.
  • Davison S, Bell R, Donath S, et al. Androgen levels in adult females: changes with age, menopause, and oophorectomy. J Clin Endocrinol Metab. 2005;90:3847–3853.
  • Arlt W. Androgen therapy in women. Eur J Endocrinol. 2006;154:1–11.
  • Hodgson T, Braunstein GD. Physiological effects of androgens in women. In: Azziz R, Nestler JE, Deqailly D, editors. Contemporary endocrinology: androgen excess disorders in women: polycystic ovary syndrome and other disorders. 2nd ed. Totowa (NJ): Totowa: NJ Humana Press Inc; 2007. p. 49–61.
  • Lobo RA. Androgens in postmenopausal women: production, possible role, and replacement options. Obstet Gynecol Surv. 2001;56:361–376.
  • Skiba MA, Bell RJ, Islam RM, et al. Androgens during the reproductive years: what is normal for women? J Clin Endocrinol Metab. 2019;104:5382–5392.
  • Davis S, Braunstein GD. Efficacy and safety of testosterone in the management of hypoactive sexual desire disorder in postmenopausal women. J Sex Med. 2012;9:1134–1148.
  • Braunstein GD, Reitz RE, Buch A, et al. Testosterone reference ranges in normally cycling healthy premenopausal women. J Sex Med. 2011;8:2924–2934.
  • Bertin J, Dury AY, Ouellet J, et al. Localization of the androgen-synthesizing enzymes, androgen receptor, and sex steroids in the vagina: possible implications for the treatment of postmenopausal sexual dysfunction. J Sex Med. 2014;11:1949–1961.
  • Berman JR, Almeida FG, Jolin J, et al. Correlation of androgen receptors, aromatase, and 5-alpha reductase in the human vagina with menopausal status. Fertil Steril. 2003;79:925–931.
  • Chang C, Lee SO, Wang RS, et al. Androgen receptor (AR) physiological roles in male and female reproductive systems: lessons learned from AR-knockout mice lacking AR in selective cells. Biol Reprod. 2013;89:21.
  • Davey RA, Grossmann M. Androgen receptor structure, function and biology: from bench to bedside. Clin Biochem Rev. 2016;37:3–15.
  • Thomas P. Membrane androgen receptors unrelated to nuclear steroid receptors. Endocrinology. 2019;160:772–781.
  • Bulldan A, Dietze R, Shihan M, et al. Non-classical testosterone signaling mediated through ZIP9 stimulates claudin expression and tight junction formation in Sertoli cells. Cell Signal. 2016;28:1075–1085.
  • Huo YN, Yeh SD, Lee WS. Androgen receptor activation reduces the endothelial cell proliferation through activating the cSrc/AKT/p38/ERK/NFκB-mediated pathway. J Steroid Biochem Mol Biol. 2019;194:105459.
  • Höfer P, Lanzenberger R, Kasper S. Testosterone in the brain: neuroimaging findings and the potential role for neuropsychopharmacology. Eur Neuropsychopharmacol. 2013;23:79–88.
  • Celec P, Ostatnikova D, Hodosy J. On the effects of testosterone on brain behavioral functions. Front Neurosci. 2015;9:12.
  • Traish AM, Botchevar E, Kim NN. Biochemical factors modulating female genital sexual arousal physiology. J Sex Med. 2010;7:2925–2946.
  • Sharma UR, Rissman EF. Testosterone implants in specific neural sites activate female sexual behaviour. J Neuroendocrinol. 1994;6:423–432.
  • Locklear MN, Michaelos M, Collins WF, et al. Gonadectomy but not biological sex affects burst-firing in dopamine neurons of the ventral tegmental area and in prefrontal cortical neurons projecting to the ventral tegmentum in adult rats. Eur J Neurosci. 2017;45:106–120.
  • Wainwright SR, Lieblich SE, Galea LA. Hypogonadism predisposes males to the development of behavioural and neuroplastic depressive phenotypes. Psychoneuroendocrinology. 2011;36:1327–1341.
  • Roselli CE, Resko JA. Aromatase activity in the rat brain: hormonal regulation and sex differences. J Steroid Biochem Mol Biol. 1993;44:499–508.
  • Maseroli E, Santangelo A, Lara-Fontes B, et al. The non-aromatizable androgen dihydrotestosterone (DHT) facilitates sexual behavior in ovariectomized female rats primed with estradiol. Psychoneuroendocrinology. 2020;115:104606.
  • Dennerstein L, Randolph J, Taffe J, et al. Hormones, mood, sexuality, and the menopausal transition. Fertil Steril. 2002;77(Suppl 4): S42–8.
  • Roney JR, Simmons ZL. Hormonal predictors of sexual motivation in natural menstrual cycles. Horm Behav. 2013;63:636–645.
  • Bramen JE, Hranilovich JA, Dahl RE, et al. Sex matters during adolescence: testosterone-related cortical thickness maturation differs between boys and girls. PLoS One. 2012;7:e33850.
  • Cappelletti M, Wallen K. Increasing women's sexual desire: the comparative effectiveness of estrogens and androgens. Horm Behav. 2016;78:178–193.
  • Nastri C, Lara LA, Ferriani RA, et al. Hormone therapy for sexual function in perimenopausal and postmenopausal women. Cochrane Database Syst Rev. 2013;5:CD009672.
  • Davis SR, Goldstat R, Papalia MA, et al. Effects of aromatase inhibition on sexual function and well-being in postmenopausal women treated with testosterone: a randomized, placebo-controlled trial. Menopause. 2006;13:37–45.
  • Levin RJ, Both S, Georgiadis J, et al. The physiology of female sexual function and the pathophysiology of female sexual dysfunction (Committee 13A). J Sex Med. 2016;13:733–759.
  • Park K, Kim N. Anatomy and physiology of arousal. In: Goldstein I, Clayton AH, Goldstein AT, et al., editors. Textbook of female sexual function and dysfunction: diagnosis and treatment. Oxford: Wiley Blackwell; 2018. p. 107–125.
  • Levin R. The pharmacology of the human female orgasm - its biological and physiological backgrounds. Pharmacol Biochem Behav. 2014;121:62–70.
  • Davis S, Worsley R, Miller KK, et al. Androgens and female sexual function and dysfunction – findings from the fourth international consultation of sexual medicine. J Sex Med. 2016;13:168–178.
  • Traish A, Vignozzi L, Goldstein I, et al. Role of androgens and estrogens in female genitourinary tract structure and function: implications in the genitourinary syndrome of menopause. Sex Med Rev. 2018;5:558–571.
  • Simon JA, Goldstein I, Kim NN, et al. The role of androgens in the treatment of genitourinary syndrome of menopause (GSM): International Society for the Study of Women's Sexual Health (ISSWSH) expert consensus panel review. Menopause. 2018;25:837–847.
  • Vignozzi L, Filippi S, Morelli A, et al. Testosterone/estradiol ratio regulates NO-induced bladder relaxation and responsiveness to PDE5 inhibitors. J Sex Med. 2012;9:3028–3040.
  • Labrie F, Martel C, Pelletier G. Is vulvovaginal atrophy due to a lack of both estrogens and androgens? Menopause. 2017;24:452–461.
  • Comeglio P, Cellai I, Filippi S, et al. Differential effects of testosterone and estradiol on clitoral function: an experimental study in rats. J Sex Med. 2016;13:1858–1871.
  • Traish AM, Kim N, Min K, et al. Role of androgens in female genital sexual arousal: receptor expression, structure, and function. Fertil Steril. 2002;77(Suppl 4): S11–S18.
  • Bachmann G, Bancroft J, Braunstein G, et al. Female androgen insufficiency: the Princeton consensus statement on definition, classification, and assessment. Fertil Steril. 2002;77:660–665.
  • Burger HG, Dudley EC, Cui J, et al. A prospective longitudinal study of serum testosterone, dehydroepiandrosterone sulfate, and sex hormone-binding globulin levels through the menopause transition. J Clin Endocrinol Metab. 2000;85:2832–2838.
  • Davis SR, Bell RJ, Robinson PJ, et al. Testosterone and estrone increase from the age of 70 years: findings from the sex hormones in older women study. J Clin Endocrinol Metab. 2019;104:6291–6300.
  • Wåhlin-Jacobsen S, Pedersen AT, Kristensen E, et al. Is there a correlation between androgens and sexual desire in women? J Sex Med. 2015;12:358–373.
  • Zheng J, Islam R, Skiba MA, et al. Associations between androgens and sexual function in premenopausal women; a cross-sectional study. Lancet Diabetes Endocrinol. 2020;8:693–702.
  • Randolph JF, Jr., Zheng H, Avis NE, et al. Masturbation frequency and sexual function domains are associated with serum reproductive hormone levels across the menopausal transition. J Clin Endocrinol Metab. 2015;100:258–266.
  • Wåhlin-Jacobsen S, Kristensen E, Pedersen AT, et al. Androgens and psychosocial factors related to sexual dysfunctions in premenopausal Women∗: ∗2016 ISSM Female Sexual Dysfunction Prize. J Sex Med. 2017;14:366–379.
  • Leiblum S, Koochaki PE, Rodenberg CA, et al. Hypoactive sexual desire disorder in postmenopausal women: US results from the women's international study of health and sexuality (WISHeS). Menopause. 2006;13:46–56.
  • Davis S, Davison SL, Donath S, et al. Circulating androgen levels and self-reported sexual function in women. JAMA. 2005;294:91–96.
  • Labrie F. Extragonadal synthesis of sex steroids: intracrinology. Ann Endocrinol (Paris). 2003;64:95–107.
  • Wåhlin-Jacobsen S, Flanagan JN, Pedersen AT, et al. Androgen receptor polymorphism and female sexual function and desire. J Sex Med. 2018;15:1537–1546.
  • Krapf JM, Simon JA. A sex-specific dose-response curve for testosterone: could excessive testosterone limit sexual interaction in women? Menopause. 2017;24:462–470.
  • Guay A, Jacobson J, Munarriz R, et al. Serum androgen levels in healthy premenopausal women with and without sexual dysfunction: Part B: Reduced serum androgen levels in healthy premenopausal women with complaints of sexual dysfunction. Int J Impot Res. 2004;16:121–129.
  • Wilke TJ, Utley DJ. Total testosterone, free-androgen index, calculated free testosterone, and free testosterone by analog RIA compared in hirsute women and in otherwise-normal women with altered binding of sex-hormone-binding globulin. Clin Chem. 1987;33:1372–1375.
  • Rosner W, Auchus RJ, Azziz R, et al. Position statement: utility, limitations, and pitfalls in measuring testosterone: an Endocrine Society position statement. J Clin Endocrinol Metab. 2007;92:405–413.
  • Rosner W, Vesper H. Toward excellence in testosterone testing: a consensus statement. J Clin Endocrinol Metab. 2010;95:4542–4548.
  • Goldman AL, Bhasin S, Wu FCW, et al. A reappraisal of testosterone's binding in circulation: physiological and clinical implications. Endocr Rev. 2017;38:302–324.
  • Somboonporn W, Davis S, Seif M, et al. Testosterone for peri- and postmenopausal women. Cochrane Database Syst Rev. 2005;4:CD004509.
  • Achilli C, Pundir J, Ramanathan P, et al. Efficacy and safety of transdermal testosterone in postmenopausal women with hypoactive sexual desire disorder: a systematic review and meta-analysis. Fertil Steril. 2017;107:475–82.e415.
  • Burger HG, Hailes J, Nelson J, et al. Effect of combined implants of oestradiol and testosterone on libido in postmenopausal women. Br Med J (Clin Res Ed). 1987;294:936–937.
  • Davis SR, McCloud PI, Strauss BJG, et al. Testosterone enhances estradiol's effects on postmenopausal bone density and sexuality. Maturitas. 1995;21:227–236.
  • Lobo R, Rosen RC, Yang H-M, et al. Comparative effects of oral esterified estrogens with and without methyl testosterone on endocrine profiles and dimensions of sexual function in postmenopausal women with hypoactive sexual desire. Fertil Steril. 2003;79:1341–1352.
  • Floter A, Nathorst-Boos J, Carlstrom K, et al. Addition of testosterone to estrogen replacement therapy in oophorectomized women: effects on sexuality and well-being. Climacteric. 2002;5:357.
  • Buckler HM, Robertson WR, Wu FC. Which androgen replacement therapy for women? J Clin Endocrinol Metab. 1998;83:3920–3924.
  • Davis SR, Moreau M, Kroll R, et al. Testosterone for low libido in menopausal women not taking estrogen therapy. N Engl J Med. 2008;359:2005–2017.
  • Fooladi E, Reuter SE, Bell RJ, et al. Pharmacokinetics of a transdermal testosterone cream in healthy postmenopausal women. Menopause. 2015;22:44–49.
  • Kingsberg S, Shifren J, Wekselman K, et al. Evaluation of the clinical relevance of benefits associated with transdermal testosterone treatment in postmenopausal women with hypoactive sexual desire disorder. J Sex Med. 2007;4:1001–1008.
  • Goldstat R, Briganti E, Tran J, et al. Transdermal testosterone therapy improves well-being, mood, and sexual function in premenopausal women. Menopause. 2003;10:390–398.
  • Fooladi E, Bell RJ, Jane F, et al. Testosterone improves antidepressant-emergent loss of libido in women: findings from a randomized, double-blind, placebo-controlled trial. J Sex Med. 2014;11:831–839.
  • Davis SR, Papalia MA, Norman RJ, et al. Safety and efficacy of a testosterone metered-dose transdermal spray for treatment of decreased sexual satisfaction in premenopausal women: a placebo-controlled randomized, dose-ranging study. Ann Intern Med. 2008;148:569–577.
  • Barrett-Connor E, Young R, Notelovitz M, et al. A two-year, double-blind comparison of estrogen-androgen and conjugated estrogens in surgically menopausal women. Effects on bone mineral density, symptoms and lipid profiles. J Reprod Med. 1999;44:1012–1020.
  • Elraiyah T, Sonbol MB, Wang Z, et al. Clinical review: the benefits and harms of systemic testosterone therapy in postmenopausal women with normal adrenal function: a systematic review and meta-analysis. J Clin Endocrinol Metab. 2014;99:3543–3550.
  • Boyd PR, Mark GJ. Multiple hepatic adenomas and a hepatocellular carcinoma in a man on oral methyl testosterone for eleven years. Cancer. 1977;40:1765–1770.
  • Pharmaceuticals V. Android C-III package insert. [cited 2020 May 8]. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/083976s032lbl.pdf.
  • Nachtigall L, Casson P, Lucas J, et al. Safety and tolerability of testosterone patch therapy for up to 4 years in surgically menopausal women receiving oral or transdermal oestrogen. Gynecol Endocrinol. 2011;27:39–48.
  • White WB, Grady D, Giudice LC, et al. A cardiovascular safety study of LibiGel (testosterone gel) in postmenopausal women with elevated cardiovascular risk and hypoactive sexual desire disorder. Am Heart J. 2012;163:27–32.
  • Pharmaceuticals B. BioSante Pharmaceuticals announces positive LibiGel phase III safety data review and decision to conclude the safety study. [cited 2019 Jun 21]. Available from: https://www.businesswire.com/news/home/20120904005404/en/BioSante-Pharmaceuticals-Announces-Positive-LibiGel%C2%AE-Phase-III.
  • Wierman M, Arlt W, Basson R, et al. Androgen therapy in women: a reappraisal: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2014;99:2489–3510.
  • Elraiyah T, Sonbol MB, Wang Z, et al. Clinical review: the benefits and harms of systemic dehydroepiandrosterone (DHEA) in postmenopausal women with normal adrenal function: a systematic review and meta-analysis. J Clin Endocrinol Metab. 2014;99:3536–3542.
  • Jayasena CN, Alkaabi FM, Liebers CS, et al. A systematic review of randomized controlled trials investigating the efficacy and safety of testosterone therapy for female sexual dysfunction in postmenopausal women. Clin Endocrinol (Oxf). 2019;90:391–414.
  • Glaser RL, Dimitrakakis C. Reduced breast cancer incidence in women treated with subcutaneous testosterone, or testosterone with anastrozole: a prospective, observational study. Maturitas. 2013;76:342–349.
  • Clayton A, Goldfischer ER, Goldstein I, et al. Validation of the decreased sexual desire screener (DSDS): a brief diagnostic instrument for generalized acquired female hypoactive sexual desire disorder (HSDD). J Sex Med. 2009;6:730–738.
  • Kingsberg SA, Althof S, Simon JA, et al. Female sexual dysfunction-medical and psychological treatments, Committee 14. J Sex Med. 2017;14:1463–1491.
  • Advisory Committee Briefing Document Intrinsa® (testosterone transdermal system) 2 December 2004. NDA No. 21–769 Procter & Gamble Pharmaceuticals, Inc. Advisory Committee for Reproductive Health Drugs. Food and Drug Administration, USA. [cited 2019 Apr 20]. Available from: http://wayback.archive-it.org/7993/20170405114619/https://www.fda.gov/ohrms/dockets/ac/04/briefing/2004-4082B1_01_A-P&G-Intrinsa.pdf.
  • Baber RJ, Panay N, Fenton A. 2016 IMS recommendations on women's midlife health and menopause hormone therapy. Climacteric. 2016;19:109–150.
  • The 2017 hormone therapy position statement of The North American Menopause Society. Menopause. 2017;24:728–753.
  • Hamoda H. The British Menopause Society and women's health concern recommendations on the management of women with premature ovarian insufficiency. Post Reprod Health. 2017;23:22–35.
  • Committee opinion no. 698: hormone therapy in primary ovarian insufficiency. Obstet Gynecol. 2017;129:e134–e141.
  • Webber L, Davies M, Anderson R, et al. ESHRE guideline: management of women with premature ovarian insufficiency. Hum Reprod. 2016;31:926–937.
  • Vujovic S, Brincat M, Erel T, et al. EMAS position statement: managing women with premature ovarian failure. Maturitas. 2010;67:91–93.
  • Nappi RE, Cucinella L, Martini E, et al. Sexuality in premature ovarian insufficiency. Climacteric. 2019;22:289–295.
  • Shifren JL, Desindes S, McIlwain M, et al. A randomized, open-label, crossover study comparing the effects of oral versus transdermal estrogen therapy on serum androgens, thyroid hormones, and adrenal hormones in naturally menopausal women. Menopause. 2007;14:985–994.
  • Taylor HS, Tal A, Pal L, et al. Effects of oral vs transdermal estrogen therapy on sexual function in early postmenopause: ancillary study of the kronos early estrogen prevention study (KEEPS). JAMA Intern Med. 2017;177:1471–1479.
  • Davis SR, Bitzer J, Giraldi A, et al. Change to either a nonandrogenic or androgenic progestin-containing oral contraceptive preparation is associated with improved sexual function in women with oral contraceptive-associated sexual dysfunction. J Sex Med. 2013;10:3069–3079.
  • Both S, Lew-Starowicz M, Luria M, et al. Hormonal contraception and female sexuality: position statements from the European Society of Sexual Medicine (ESSM). J Sex Med. 2019;16:1681–1695.
  • Braunstein GD. Safety of testosterone treatment in postmenopausal women. Fertil Steril. 2007;88:1–17.
  • Shifren JL, Braunstein GD, Simon JA, et al. Transdermal testosterone treatment in women with impaired sexual function after oophorectomy. N Engl J Med. 2000;343:682–688.
  • Grober ED, Garbens A, Božović A, et al. Accuracy of testosterone concentrations in compounded testosterone products. J Sex Med. 2015;12:1381–1388.
  • National Academies of Sciences Engineering and Medicine. The clinical utility of compounded bioidentical hormone therapy: a review of safety, effectiveness, and use. The National Academies Press; 2020. [cited 2020 Sep 23]. Available from: https://www.nap.edu/catalog/25791/the-clinical-utility-of-compounded-bioidentical-hormone-therapy-a-review.
  • Nathorst-Boos J, Floter A, Jarkander-Rolff M, et al. Treatment with percutanous testosterone gel in postmenopausal women with decreased libido-effects on sexuality and psychological general well-being. Maturitas. 2006;53:11–18.
  • Vegunta S, Kling JM, Kapoor E. Androgen therapy in women. J Womens Health (Larchmt). 2020;29:57–64.
  • Parish SJ, Nappi RE, Kingsberg S. Perspectives on counseling patients about menopausal hormone therapy: strategies in a complex data environment. Menopause. 2018;25:937–949.
  • Guay A, Munarriz R, Jacobson J, et al. Serum androgen levels in healthy premenopausal women with and without sexual dysfunction: part A. Serum androgen levels in women aged 20-49 years with no complaints of sexual dysfunction. Int J Impot Res. 2004;16:112–120.
  • Platz EA, Barber JR, Chadid S, et al. Nationally representative estimates of serum testosterone concentration in never-smoking, lean men without aging-associated comorbidities. J Endocr Soc. 2019;3:1759–1770.
  • Lewis T, Goldstein I. Transfer of topical testosterone preparations to children or spouses. J Sex Med. 2009;6:2649–2652.
  • Rosen R, Brown C, Heiman J, et al. The female sexual function index (FSFI): a multidimensional self-report instrument for the assessment of female sexual function. J Sex Marital Ther. 2000;26:191–208.
  • Derogatis L, Clayton A, Lewis-D'Agostino D, et al. Validation of the female sexual distress scale-revised for assessing distress in women with hypoactive sexual desire disorder. J Sex Med. 2008;5:357–364.
  • Kennedy RG, Davies T, Al-Azzawi F. Sexual interest in postmenopausal women is related to 5alpha-reductase activity. Hum Reprod. 1997;12:209–213.
  • Shifren J, Davis S, Moreau M, et al. Testosterone patch for the treatment of hypoactive sexual desire disorder in naturally menopausal women: results from the INTIMATE NM1 study. Menopause. 2006;13:770–779.
  • Schmidt U, Nygaard B, Jensen EW, et al. Peripheral markers of thyroid function: the effect of T4 monotherapy vs T4/T3 combination therapy in hypothyroid subjects in a randomized crossover study. Endocr Connect. 2013;2:55–60.
  • Selva D, Hammond GL. Thyroid hormones act indirectly to increase sex hormone-binding globulin production by liver via hepatocyte nuclear factor-4alpha. J Mol Endocrinol. 2009;43:19–27.
  • Hampl R, Kancheva R, Hill M, et al. Interpretation of sex hormone-binding globulin levels in thyroid disorders. Thyroid. 2003;13:755–760.
  • Hormonology Department, University Hospital of Ghent, Belgium, Belgium. Free & bioavailable testosterone calculator. [cited 2020 Mar 29]. Available from: http://www.issam.ch/freetesto.htm.
  • Muka T, Nano J, Jaspers L, et al. Associations of steroid sex hormones and sex hormone-binding globulin with the risk of type 2 diabetes in women: a population-based cohort study and meta-analysis. Diabetes. 2017;66:577–586.
  • Kische H, Gross S, Wallaschofski H, et al. Clinical correlates of sex hormones in women: the study of health in Pomerania. Metabolism. 2016;65:1286–1296.
  • Basson R, Wierman ME, van Lankveld J, et al. Summary of the recommendations on sexual dysfunctions in women. J Sex Med. 2010;7:314–326.
  • Peixoto C, Carrilho CG, Barros JA, et al. The effects of dehydroepiandrosterone on sexual function: a systematic review. Climacteric. 2017;20:129–137.
  • Portman DJ, Goldstein SR, Kagan R. Treatment of moderate to severe dyspareunia with intravaginal prasterone therapy: a review. Climacteric. 2019;22:65–72.
  • Sauer U, Talaulikar V, Davies MC. Efficacy of intravaginal dehydroepiandrosterone (DHEA) for symptomatic women in the peri- or postmenopausal phase. Maturitas. 2018;116:79–82.
  • Simon JA. Implementing a successful clinical development program for female sexual dysfunctions (aka how to navigate a regulatory minefield). Maturitas. 2011;69:97–98.