The non-aromatizable androgen dihydrotestosterone (DHT) facilitates sexual behavior in ovariectomized female rats primed with estradiol

Maseroli, Elisa; Santangelo, Andrea; Lara-Fontes, Beatriz; Quintana, Gonzalo R.; Cionnaith, Conall E. Mac; Casarrubea, Maurizio; Ricca, Valdo; Maggi, Mario; Vignozzi, Linda; Pfaus, James G.

doi:10.1016/j.psyneuen.2020.104606

Cited by 24 publications

(8 citation statements)

References 45 publications

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“…62 However, a recent study demonstrates that treating ovariectomized rats with the nonaromatizable androgen 5a-DHT enhanced female sexual activity while significantly improving both appetitive and receptive behaviors. 63 Thus, the function of key brain regions that regulate both motivation and reward are testosterone dependent and mainly mediated by the activation of the AR.…”

Section: Mechanism Of Action Of Sex Steroids Central Mechanisms In Animal Modelsmentioning

confidence: 99%

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

Parish

Simon

Davis

et al. 2021

The Journal of Sexual Medicine

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Background:The Global Consensus Position Statement on the Use of Testosterone Therapy for Women (Global Position Statement) recommended testosterone therapy for postmenopausal women with hypoactive sexual desire disorder (HSDD). 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 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

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Section: Mechanism Of Action Of Sex Steroids Central Mechanisms In Animal Modelsmentioning

confidence: 99%

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

Parish

Simon

Davis

et al. 2021

The Journal of Sexual Medicine

Self Cite

View full text Add to dashboard Cite

show abstract

“…The action of testosterone may also be prolonged by estrogen, as is evidenced by the observation that estradiol increases the duration of AR occupation by 5a-DHT in the medial preoptic area, a key brain region regulating sexual behavior [62]. However, a recent study demonstrates that treating ovariectomized rats with the non-aromatizable androgen 5a-DHT enhanced female sexual activity while significantly improving both appetitive and receptive behaviors [63]. Thus, the function of key brain regions that regulate both motivation and reward are testosterone-dependent and mainly mediated by the activation of the AR.…”

Section: Central Mechanisms In Animal Modelsmentioning

confidence: 99%

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

et al. 2021

Self Cite

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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.

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“…In hypogonadal men with erectile dysfunction, TRT was able to improve penile vasodilation as assessed using color Doppler ultrasound (CDU) [ 16 , 17 ]. In contrast, despite the clinical evidence and the current consensus on the central effect of T on female sexual desire [ 3 , 18 ], the mechanisms by which androgens may directly act in relevant female brain areas have not been elucidated [ 19 ]. Recently, a study from our group demonstrated that the androgen receptor (AR) super-agonist dihydrotestosterone (DHT), which is not aromatizable to estrogen, was able to stimulate sexual behaviors in ovariectomized female rats [ 19 ], therefore suggesting that conversion into estrogens is not required for the facilitatory effect of androgens on sexual desire [ 19 ].…”

Section: Introductionmentioning

confidence: 99%

“…In contrast, despite the clinical evidence and the current consensus on the central effect of T on female sexual desire [ 3 , 18 ], the mechanisms by which androgens may directly act in relevant female brain areas have not been elucidated [ 19 ]. Recently, a study from our group demonstrated that the androgen receptor (AR) super-agonist dihydrotestosterone (DHT), which is not aromatizable to estrogen, was able to stimulate sexual behaviors in ovariectomized female rats [ 19 ], therefore suggesting that conversion into estrogens is not required for the facilitatory effect of androgens on sexual desire [ 19 ]. In vivo systemic T treatment in ovariectomized rats also improves the relaxation of clitoral vascular smooth muscle cells (SMCs) through the nitric oxide (NO)—cyclic guanosine monophosphate (cGMP) pathway, thus sustaining the major relaxant mechanisms involved in genital sexual arousal [ 20 ].…”

Section: Introductionmentioning

confidence: 99%

Effects of testosterone treatment on clitoral haemodynamics in women with sexual dysfunction

Cipriani

Maseroli

Stasi

et al. 2021

J Endocrinol Invest

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Purpose To explore the effects of 6-month systemic testosterone (T) administration on clitoral color Doppler ultrasound (CDU) parameters in women with female sexual dysfunction (FSD). Methods 81 women with FSD were retrospectively recruited. Data on CDU parameters at baseline and after 6 months with four different treatments were available and thus further longitudinally analyzed: local non-hormonal moisturizers (NH group), n = 37; transdermal 2% T gel 300 mcg/day (T group), n = 23; local estrogens (E group), n = 12; combined therapy (T + E group), n = 9. Patients underwent physical, laboratory, and genital CDU examinations at both visits and completed different validated questionnaires, including the Female Sexual Function Index (FSFI). Results At 6-month visit, T therapy significantly increased clitoral artery peak systolic velocity (PSV) when compared to both NH (p < 0.0001) and E (p < 0.0001) groups. A similar increase was found in the T + E group (p = 0.039 vs. E). In addition, T treatment was associated with significantly higher FSFI desire, pain, arousal, lubrication, orgasm, and total scores at 6-month visit vs. baseline. Similar findings were observed in the T + E group. No significant differences in the variations of total and high-density lipoprotein-cholesterol, triglycerides, fasting glycemia, insulin and glycated hemoglobin levels were found among the four groups. No adverse events were observed. Conclusion In women complaining for FSD, systemic T administration, either alone or combined with local estrogens, was associated with a positive effect on clitoral blood flow and a clinical improvement in sexual function, showing a good safety profile. Trial registration number NCT04336891; date of registration: April 7, 2020.

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The non-aromatizable androgen dihydrotestosterone (DHT) facilitates sexual behavior in ovariectomized female rats primed with estradiol

Cited by 24 publications

References 45 publications

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

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

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

Effects of testosterone treatment on clitoral haemodynamics in women with sexual dysfunction

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