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

Abstract

Aim

To provide a clinical practice guideline for the use of testosterone including identification of patients, laboratory testing, dosing, post-treatment monitoring, and follow-up care in women with hypoactive sexual desire disorder (HSDD).

Methods

The International Society for the Study of Women's Sexual Health appointed a multidisciplinary panel of experts who performed a literature review of original research, meta-analyses, review papers, and consensus guidelines regarding testosterone use in women. Consensus was reached using a modified Delphi method.

Outcomes

A clinically useful guideline following a biopsychosocial assessment and treatment approach for the safe and efficacious use of testosterone in women with HSDD was developed including measurement, indications, formulations, prescribing, dosing, monitoring, and follow-up.

Results

Although the Global Position Statement endorses testosterone therapy for only postmenopausal women, limited data also support the use in late reproductive age premenopausal women, consistent with the International Society for the Study of Women's Sexual Health Process of Care for the Management of HSDD. Systemic transdermal testosterone is recommended for women with HSDD not primarily related to modifiable factors or comorbidities such as relationship or mental health problems. Current available research supports a moderate therapeutic benefit. Safety data show no serious adverse events with physiologic testosterone use, but long-term safety has not been established. Before initiation of therapy, clinicians should provide an informed consent. Shared decision-making involves a comprehensive discussion of off-label use, as well as benefits and risks. A total testosterone level should not be used to diagnose HSDD, but as a baseline for monitoring. Government-approved transdermal male formulations can be used cautiously with dosing appropriate for women. Patients should be assessed for signs of androgen excess and total testosterone levels monitored to maintain concentrations in the physiologic premenopausal range. Compounded products cannot be recommended because of the lack of efficacy and safety data.

Clinical implications

This clinical practice guideline provides standards for safely prescribing testosterone to women with HSDD, including identification of appropriate patients, dosing, and monitoring.

Strengths and limitations

This evidence-based guideline builds on a recently published comprehensive meta-analysis and the Global Position Statement endorsed by numerous societies. The limitation is that testosterone therapy is not approved for women by most regulatory agencies, thereby making prescribing and proper dosing challenging.

Conclusion

Despite substantial evidence regarding safety, efficacy, and clinical use, access to testosterone therapy for the treatment of HSDD in women remains a significant unmet need.

国际女性性健康研究学会采用全身性睾酮治疗女性性欲减退的临床实践指南 摘要

目的：为应用睾酮提供临床实践指南, 包括对性欲减退症（HSDD）患者的识别、实验室检测、剂量、治疗后监测和随访护理。

方法：国际女性性健康研究学会任命了一个多学科专家小组, 他们对有关女性睾酮应用的原始研究、meta分析、综述论文和共识指南进行了文献综述。应用改进的德尔菲法达成共识。

结果：根据生物心理社会评估和治疗方法, 为HSDD女性患者安全有效地应用睾酮制定了一项临床有用的指南, 包括测量、适应证、配方、处方、剂量、监测和随访。

结果：尽管全球立场声明支持睾酮疗法仅适用于绝经后女性, 但有限的数据也支持将其用于育龄期晚期绝经前女性, 这与国际女性性健康护理程序研究学会的HSDD管理方案是一致的。对于主要与可改变因素或合并症（如人际关系或心理健康问题）无关的HSDD女性, 建议应用全身经皮睾酮。目前可用的研究支持适度的治疗益处。安全性数据显示, 应用生理性睾酮没有严重的不良反应, 但长期安全性尚未确定。在开始治疗之前, 临床医生应提供知情同意书。共同决策涉及对超适应证应用以及益处和风险的全面讨论。总睾酮水平不应用于诊断HSDD, 而应作为监测的基线。政府批准的男性透皮制剂可以谨慎应用, 剂量适合女性。应该评估患者是否有雄激素过剩的迹象, 并监测总睾酮水平, 以将浓度维持在生理绝经前的范围内。由于缺乏疗效和安全性数据, 不能推荐复合产品。

临床意义：本临床实践指南提供了为HSDD女性安全开具睾酮处方的标准, 包括确定合适的患者、剂量和监测。

优点和局限性：这份基于证据的指南建立在最近发表的一项全面的meta分析和众多社会认可的全球立场声明的基础上。限制是大多数监管机构未批准女性应用睾酮, 因此使得处方和适当剂量具有挑战性。

Keywords:

• Systemic testosterone
• hypoactive sexual desire disorder
• clinical practice guideline
• female sexual dysfunction
• ISSWSH

Acknowledgements

These Guidelines have been copublished with permission in The Journal of Sexual Medicine, Journal of Women's Health, and Climacteric. The authors would like to thank Tessa Benitez, Executive Director of ISSWSH.

Potential conflict of interest

SJP: Consultant: AMAG Pharmaceuticals, Strategic Science & Technologies; Writing support, no compensation: AMAG Pharmaceuticals, Sprout Pharmaceuticals, TherapeuticsMD; JAS: AbbVie, Inc, AMAG Pharmaceuticals, Inc, Bayer Healthcare LLC., CEEK Enterprises, LLC., Covance Inc, Daré Bioscience, Duchesnay USA, Endoceutics, Inc, GTx, Inc, Hologic Inc, Ipsen, KaNDy/NeRRe Therapeutics Ltd, Mitsubishi Tanabe Pharma Development America, Inc, Madorra Pty Ltd, Myovant Sciences, ObsEva SA, Shionogi Inc, Sprout2 Inc, TherapeuticsMD, Viveve Medical; Stockholder (direct purchase) in Sermonix Pharmaceuticals; SRD: Honoraria: Besins Healthcare, Pfizer Australia; Consultant: Mayne Pharmaceuticals, Lawley Pharmaceuticals, Que Oncology; Institutional Grant: Que Oncology research; AG: Consultant: Eli Lilly, Palatin. Speakers Bureau: Pfizer, Astellas; IG: Research: Marius, AbbVie, Consultant: Lipocine, Speakers Bureau: Clarus; SWG: Research: Marius, AbbVie; NNK: None; SAK: AMAG, Astellas, Daré, Duchesney, Emotional Brain, Endoceutics, Ovoca, Lupin, Materna, Palatin Technologies, Pfizer, Sprout, Strategic Science Technologies, TherapeuticsMD, Viveve, Mitsubishi Tanabe NA; AM: Acerus, Antares, Clarus, Research: Endo; REN: Consultant/speaker: Astellas, Bayer HealthCare AG, Exceltis, Fidia, Merck Sharpe & Dohme, Novo Nordisk, Palatin Technologies, Pfizer Inc, Shionogi Limited and Theramex; KP: None; CAS: None; AT: None; LV: Research: Lipocine, Bayer, Kyowa Kirin.

Source of funding

ISSWSH, a portion of which came from an unrestricted educational grant from Lawley Pharmaceuticals. Susan R. Davis is an NHMRC Senior Principal Research Fellow (Grant No. 1135843).

Statement of authorship

Sharon J. Parish: Conceptualization, Investigation, Writing - Original Draft, Writing - Review & Editing, Supervision, Project Administration; James A. Simon: Conceptualization, Investigation, Writing - Original Draft, Writing - Review & Editing, Supervision, Project Administration; Susan R. Davis: Investigation, Writing - Original Draft, Writing - Review & Editing; Annamaria Giraldi: Investigation, Writing - Original Draft, Writing - Review & Editing; Irwin Goldstein: Investigation, Writing - Original Draft, Writing - Review & Editing; Sue W. Goldstein: Investigation, Writing - Original Draft, Writing - Review & Editing, Supervision, Project Administration, Funding Acquisition; Noel N. Kim: Investigation, Writing - Original Draft, Writing - Review & Editing; Sheryl A. Kingsberg: Investigation, Writing - Original Draft, Writing - Review & Editing; Abraham Morgentaler: Investigation, Writing - Original Draft, Writing - Review & Editing; Rossella E. Nappi: Investigation, Writing - Original Draft, Writing - Review & Editing; Kwangsung Park: Investigation, Writing - Original Draft, Writing - Review & Editing; Cynthia A. Stuenkel: Investigation, Writing - Original Draft, Writing - Review & Editing; Abdulmaged M. Traish: Investigation, Writing - Original Draft, Writing - Review & Editing; Linda Vignozzi: Investigation, Writing - Original Draft, Writing - Review & Editing.