madman
Super Moderator
Abstract
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 the 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 visits 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 of 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.
Introduction
Female sexual dysfunction (FSD) is a multifactorial condition in which organic, relational, and psychosocial factors are deeply intertwined. Among organic factors, hormonal unbalance has a major impact on FSD development. In particular, a subtle and progressive age-dependent decline of androgen levels has been implicated in the pathogenesis of both Hypoactive Sexual Desire Disorder (HSDD) [1] and Genitourinary Syndrome of Menopause (GSM) [2], whose prevalence increases with age [3, 4]. However, the diagnosis of androgen deficiency in women is controversial. In 2014, the Endocrine Society Clinical Practice Guideline recommended against making a clinical diagnosis of androgen deficiency syndrome in healthy women, since there is a lack of well-defined criteria [5], as opposed to men [6]. In fact, a biochemical definition of female androgen deficiency is not completely reliable, because of the lack of standardized, accurate assays for androgens at the low levels characteristic of women and, as well, the lack of valid reference ranges [5]. Nevertheless, when considering an evidence-based-medicine approach to this topic, several findings count in favor of the existence of a clinically manifest hypoandrogenism in women. Postmenopausal women reporting a low sexual desire have represented the main study population so far taken into account to demonstrate that female sexual function is a target of androgen action [5]. According to the definition of HSDD developed by the International Society for the Study of Women Sexual Health (ISSWSH) nomenclature committee, this condition can manifest as any of the following for a minimum of 6 months: lack of motivation for sexual activity (decreased/absent spontaneous or reactive to erotic stimulation desire); loss of desire to initiate or participate in sexual activity, not as a consequence of sexual pain disorders; combination with clinically significant personal distress [1]. Strong clinical evidence supports the use of testosterone (T) treatment for HSDD in postmenopause [3], whilst only some studies describe its clinical efficacy also in peri- and premenopausal patients [7]. Specifically, it has been reported that T treatment significantly influences multiple domains of sexual functioning, by improving desire, arousal, lubrication, pain, orgasm, and satisfaction [8–11].
In hypogonadal men, the use of T replacement therapy (TRT) is currently well established and it is strongly recommended to induce/maintain secondary sex characteristics and to correct symptoms of T deficiency [12]. The molecular pathways underlying the effects of T on male sexual function have been largely elucidated; in particular, the erectile response to T is mediated at both central (through an effect on sexual desire) and peripheral (through the effect of vasorelaxant mechanisms on penile corpora cavernosa) level [13–15]. 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 aromatized to estrogen, was able to stimulate sexually 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]. These findings strongly indicate that T could exert a positive peripheral effect on sexual response also in females, as previously observed in the male gender. However, clinical studies aimed at evaluating whether T treatment could improve clitoral blood flow are still lacking.
For these reasons, we conducted a pilot explorative research on women seeking medical care for HSDD and treated with systemic T. The primary aim of the study was to evaluate whether T treatment is associated with a change in peak systolic velocity (PSV) of the clitoral artery as assessed by CDU and whether this change is different from that observed in other treatment regimens. Psychosexual, biochemical, and metabolic parameters were also evaluated to assess the clinical efficacy and cardio-metabolic safety of T treatment.
Conclusions
In conclusion, the present study showed for the first time that a 6-month systemic T treatment, either alone or combined with estrogens, positively and directly modulated clitoral blood flow, also independently of sexual stimulation, in a small population of women complaining about sexual dysfunction. Moreover, systemic therapy with T was associated with a clinical general improvement in sexual function, as assessed by FSFI. Interestingly, no metabolic alterations or severe adverse events were detected in our study population at the 6-month visit, suggesting that T treatment is characterized by a solid safety level. However, the topic of T treatment in women needs other more in-depth research, and specifically designed randomized trials are needed to confirm our original findings.
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 the 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 visits 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 of 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.
Introduction
Female sexual dysfunction (FSD) is a multifactorial condition in which organic, relational, and psychosocial factors are deeply intertwined. Among organic factors, hormonal unbalance has a major impact on FSD development. In particular, a subtle and progressive age-dependent decline of androgen levels has been implicated in the pathogenesis of both Hypoactive Sexual Desire Disorder (HSDD) [1] and Genitourinary Syndrome of Menopause (GSM) [2], whose prevalence increases with age [3, 4]. However, the diagnosis of androgen deficiency in women is controversial. In 2014, the Endocrine Society Clinical Practice Guideline recommended against making a clinical diagnosis of androgen deficiency syndrome in healthy women, since there is a lack of well-defined criteria [5], as opposed to men [6]. In fact, a biochemical definition of female androgen deficiency is not completely reliable, because of the lack of standardized, accurate assays for androgens at the low levels characteristic of women and, as well, the lack of valid reference ranges [5]. Nevertheless, when considering an evidence-based-medicine approach to this topic, several findings count in favor of the existence of a clinically manifest hypoandrogenism in women. Postmenopausal women reporting a low sexual desire have represented the main study population so far taken into account to demonstrate that female sexual function is a target of androgen action [5]. According to the definition of HSDD developed by the International Society for the Study of Women Sexual Health (ISSWSH) nomenclature committee, this condition can manifest as any of the following for a minimum of 6 months: lack of motivation for sexual activity (decreased/absent spontaneous or reactive to erotic stimulation desire); loss of desire to initiate or participate in sexual activity, not as a consequence of sexual pain disorders; combination with clinically significant personal distress [1]. Strong clinical evidence supports the use of testosterone (T) treatment for HSDD in postmenopause [3], whilst only some studies describe its clinical efficacy also in peri- and premenopausal patients [7]. Specifically, it has been reported that T treatment significantly influences multiple domains of sexual functioning, by improving desire, arousal, lubrication, pain, orgasm, and satisfaction [8–11].
In hypogonadal men, the use of T replacement therapy (TRT) is currently well established and it is strongly recommended to induce/maintain secondary sex characteristics and to correct symptoms of T deficiency [12]. The molecular pathways underlying the effects of T on male sexual function have been largely elucidated; in particular, the erectile response to T is mediated at both central (through an effect on sexual desire) and peripheral (through the effect of vasorelaxant mechanisms on penile corpora cavernosa) level [13–15]. 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 aromatized to estrogen, was able to stimulate sexually 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]. These findings strongly indicate that T could exert a positive peripheral effect on sexual response also in females, as previously observed in the male gender. However, clinical studies aimed at evaluating whether T treatment could improve clitoral blood flow are still lacking.
For these reasons, we conducted a pilot explorative research on women seeking medical care for HSDD and treated with systemic T. The primary aim of the study was to evaluate whether T treatment is associated with a change in peak systolic velocity (PSV) of the clitoral artery as assessed by CDU and whether this change is different from that observed in other treatment regimens. Psychosexual, biochemical, and metabolic parameters were also evaluated to assess the clinical efficacy and cardio-metabolic safety of T treatment.
Conclusions
In conclusion, the present study showed for the first time that a 6-month systemic T treatment, either alone or combined with estrogens, positively and directly modulated clitoral blood flow, also independently of sexual stimulation, in a small population of women complaining about sexual dysfunction. Moreover, systemic therapy with T was associated with a clinical general improvement in sexual function, as assessed by FSFI. Interestingly, no metabolic alterations or severe adverse events were detected in our study population at the 6-month visit, suggesting that T treatment is characterized by a solid safety level. However, the topic of T treatment in women needs other more in-depth research, and specifically designed randomized trials are needed to confirm our original findings.
. Then you know that you've got to the right place. As an aside, in a relationship (no matter the gender or mix of genders), if one person in the relationship is "tuned up" with their hormones, and the other is not, it can lead to immense sexual frustration. I would urge that both individuals get their hormones and libidos on the same page
