Testosterone Therapy In Women Research Articles

Testosterone therapy in females is not associated with increased cardiovascular or breast cancer risk: a claims database analysis.

Testosterone therapy (TTh) has been shown to improve libido in women with sexual dysfunction, but its utilization has been limited due to concern for cardiovascular events and past studies reporting highly variable results. To assess the association of TTh in women with major adverse cardiac events (MACEs), including heart attack, stroke, or death, using a large database. The TriNetX Diamond Network was queried from 2009 to 2022. Our study cohort included adult females with ≥3 systemic testosterone prescriptions within a year. Our control cohort excluded females with any testosterone prescriptions, polycystic ovary syndrome, or androgen excess. Both cohorts excluded females with prior heart failure, unstable angina, intersex surgery (female to male), personal history of sex reassignment, or gender identity disorders. Propensity matching between the cohorts was performed. A subanalysis by age was conducted (18-55 and >55 years). We evaluated the association of TTh to the following: MACE, upper or lower emboli or deep vein thrombosis (DVT), pulmonary embolism (PE), breast neoplasm, and hirsutism within 3 years of TTh. When compared with propensity-matched controls, adult females with TTh had a lower risk of MACE (risk ratio [RR], 0.64; 95% CI, 0.51-0.81), DVT (RR, 0.61; 95% CI, 0.42-0.90), PE (RR, 0.48; 95% CI, 0.28-0.82), and malignant breast neoplasm (RR, 0.48; 95% CI, 0.37-0.62). Similarly, females aged 18 to 55 years with TTh had a lower risk of MACE (RR, 0.49; 95% CI, 0.28-0.85) and DVT (RR, 0.48; 95% CI, 0.25-0.93) and a similar risk of malignant breast neoplasm (RR, 0.62; 95% CI, 0.34-1.12). Females aged ≥56years with TTh had a similar risk of MACE (RR, 0.84; 95% CI, 0.64-1.10), DVT (RR, 0.82; 95% CI, 0.50-1.36), and PE (RR, 0.52; 95% CI, 0.26-1.05) and a significantly lower risk of malignant breast neoplasm (RR, 0.51; 95% CI, 0.38-0.68). Risk of hirsutism was consistently higher in those with TTh as compared with propensity-matched controls. Our results contribute to safety data on TTh, a therapy for sexual dysfunction in women. The TriNetX Diamond Network allows for significant generalizability but has insufficient information for some factors. We found a decreased risk of MACE among women with TTh as compared with matched controls and a similar risk of MACE in postmenopausal women while demonstrating a similar or significantly lower risk of breast cancer on age-based subanalysis.

(014) Testosterone Therapy in Females Is Not Associated with Increased Cardiovascular Risk – A US Claims Database Analysis

Abstract Introduction Testosterone therapy (TT) has been shown to improve libido in females with sexual dysfunction; however, utilization of TT has been limited in part due to concern for increased cardiovascular risk. Objective Our objective was to assess the association of TT in females with major adverse cardiac events (MACE) using a large claims database. Methods A US-based claims database (TriNetX Diamond Network) of over 200 million patients was queried from 2009 to 2022. Our study cohort included adult (18+) females with three or more injectable or topical testosterone prescriptions excluding those with heart failure (ICD-10 I50), unstable angina (I20.0), intersex surgery female to male (CPT 55980), personal history of sex reassignment (Z87.890), and gender identity disorders (F64). Our control cohort excluded females with any testosterone prescriptions, heart failure, intersex surgery female to male, personal history of sex reassignment, gender identity disorder, unstable angina, polycystic ovary syndrome (E28.2), or androgen excess (E28.1). Propensity-matching between the cohorts was performed for age, ethnicity, race, estrogen usage (HS300), family history of cardiovascular disease (Z82.4), tobacco usage (Z72.0), type 2 diabetes (E11), hyperlipidemia (E78), hypertensive diseases (I10-16), and utilization of outpatient (1013626), inpatient (1013659), or emergency department services (1013711). MACE was defined as heart attack (I21, I22), stroke (I60, I61, I62, I63), or death within three years of the index event. We evaluated the association of TT to MACE, upper or lower emboli or DVT (I82.4, I82.6), pulmonary embolism (PE) (I26), breast neoplasm (C50), and hirsutism (L68.0). A sub-analysis by age-based stratification (18-55-year-old and >55-year-old) was also conducted. Results Adult females with ≥3 testosterone prescriptions (n=8,457) were compared to an equivalent number of propensity-score matched controls (Table 1). Compared to matched controls, those with testosterone prescriptions had similar odds of MACE (odds ratio (OR) 0.80 [95% CI 0.60, 1.07]) and PE (OR 0.77 [0.41, 1.46]); significantly lower odds of upper or lower emboli or DVT (OR 0.59 [0.35, 0.99]) and breast neoplasm (OR 0.43 [0.32, 0.59]); and higher odds of hirsutism (OR 2.34 [1.28, 4.29]). This trend remained in the age 18-55 years group (n=5,951): MACE (OR 0.67 [0.37, 1.21]), breast neoplasm (OR 0.41 [0.24, 0.70]), and hirsutism (OR 1.45 [0.79, 2.64]) (Table 2). A similar trend was observed amongst >55-year-olds (n=2,582): MACE (OR 1.18 [0.81, 1.72]), upper or lower emboli or DVT (OR 0.89 [0.45, 1.75]), and breast neoplasm (OR 0.49 [0.33, 0.72]) (Table 2). Odds ratios could not be calculated for any patient counts less than 10 (Table 2). Conclusions In this large claims-based analysis, we showed systemic TT in women does not increase the odds of MACE or PE, and is protective against upper and lower emboli or DVTs and breast neoplasm. Our results suggest that TT in women may be safe, enabling physicians to provide appropriate therapy to women with sexual dysfunction. Disclosure No

Testosterone therapy for women

Testosterone therapy for women

Eficacia y seguridad de la testosterona en el tratamiento del deseo sexual hipoactivo en mujeres: ¿qué dice la evidencia?

ObjectiveTo determine the efficacy and safety of testosterone in the treatment of hypoactive sexual desire in women. Materials and methodsA systematic review of the literature was carried out in different electronic databases (CINAHL, DynaMed, EMBASE, Lilacs, Medline, Scopus, among others), between January 1990 and May 2021; through standardized search terms. The outcomes evaluated included the efficacy and safety of testosterone in increasing sexual desire, the total number of satisfactory sexual activity, the number of orgasms and the level of distress in patients with hypoactive sexual desire and the proportion of adverse reactions. Results72 articles were included. The use of testosterone, in postmenopausal women, with hypoactive sexual desire, reports a positive effect on sexual function, with significant increases in satisfactory sexual activity, as well as improvement in all domains of sexual function (desire, arousal and orgasmic response) and a decrease in personal anguish, with an increase in the Female Sexual Function Index score. In women of childbearing age, testosterone is formulated for “off-label” use, in such a way that compounds and doses designed for treatments in men or magisterial formulas are used (which are not approved by consensus groups or endorsed by research), but has not shown any effect on sexual function. The most frequent adverse reactions are usually hirsutism and acne, although in general testosterone, at physiological doses, has a favorable safety profile. ConclusionsTestosterone is an effective and safe therapy in the treatment of hypoactive sexual desire disorder in women after menopause. Currently there are no studies available to support the use of testosterone therapy in women of reproductive age, therefore, its use is not approved.

Testosterone Therapy in Women: A Clinical Challenge.

Testosterone Therapy in Women: A Clinical Challenge.

Pharmacotherapy for Sexual Dysfunction in Women.

This review article discusses the controversy in the DSM-5 conceptualization and diagnostic criteria for female sexual dysfunction (FSD). An overview of recent studies on available treatments for hypoactive sexual desire disorder (HSDD), female sexual arousal disorder (FSAD), and genitopelvic pain/penetration disorder (GPPD) is provided. Include delineation of the process of care for pre- and postmenopausal women with HSDD; release of global position statement on testosterone therapy in women; updates on efficacy and safety of vaginal estrogen for genitourinary syndrome of menopause and bremelanotide for HSDD; removal of flibanserin alcohol REMS; and development of new technology to enhance bioavailability and brain delivery of treatments. The DSM-5 revision combining HSDD and FSAD into one diagnostic category is a less accurate characterization of these separate disorders and may hinder access to demonstrated effective treatments for the women with these conditions. There are a wide range of pharmacological, other physiological, and psychological treatment options available for women with FSD, which can be offered based on their specific symptoms, potential benefits/risks, and preferences.

Testosterone Therapy for Women: Still Many Questions to be Answered.

Testosterone Therapy for Women: Still Many Questions to be Answered.

Testosterone Therapy in Women: A Clinical Challenge.

The physiology of testosterone as a normal female hormone in reproductive years and beyond is poorly taught and understood. This has led to unregulated and dangerous prescribing practices by physicians and other health care professionals. There are data for safe use, and as women's health care practitioners, we owe it to our patients to follow these guidelines and practices, as well as advocate for more research and safer, regulated products to prescribe.

The Role of Testosterone in Menopause Management: A Review of Literature

Background: Despite the lack of approved testosterone formulations for women in most countries, testosterone therapy is still being offered to women worldwide. Aging and loss of ovarian or adrenal function, among others, can lower testosterone levels in women. However, international guidelines currently do not routinely recommend androgen replacement therapy due to lack of long-term safety data. Evidence on its benefits and risks still remains uncertain. Objectives: The aim of this literature review is to present current studies and guidelines that examined the effects of testosterone therapy for postmenopausal women, including its role on cognition and mood; breast and endometrial cancer risks; musculoskeletal, cardiovascular, and genitourinary health; and sexual function. Methodology: A review of literature was done using PubMed, EMBASE, Science Direct, OVID, and Google scholar, with the following key words: androgen, testosterone, menopause, and hypoactive sexual desire dysfunction. We identified reviews, clinical trials, and guidelines. The population was limited to postmenopausal women. Results: There is no evidence from current published literature to support the use of testosterone therapy for female well-being, mood and cognition, bone and cardiovascular health. Intravaginal testosterone appears to be a promising alternative for the treatment of genitourinary symptoms of menopause (GSM) but efficacy and safety are yet to be confirmed. Well-designed, randomized, and placebo-controlled trials are needed to establish long-term safety, efficacy, and appropriate dosing and route of testosterone therapy in postmenopausal women. The only evidence-based indication for testosterone therapy in women is for the treatment of postmenopausal hypoactive sexual desire disorder (HSDD). Should a trial of testosterone therapy be given for HSDD, the transdermal route is the preferred method of delivery. Baseline total testosterone concentration should be determined before starting treatment, and repeated after 3–6 months. Serum testosterone levels should be monitored at regular intervals to avoid supraphysiologic dosing. Conclusion: Currently, there is no robust evidence to support the use of exogenous testosterone to improve female well-being, musculoskeletal health, mood and cognition, as well as bone and cardiovascular health among postmenopausal women. The only evidence-based indication for testosterone therapy in women is the treatment of postmenopausal hypoactive sexual desire disorder, but only after all other causes of sexual dysfunction have been ruled out. To date, testosterone therapy has no US Food and Drug Administration (US FDA) approval due to the lack of long-term efficacy and safety data.

A multi-center trial of exercise and testosterone therapy in women after hip fracture: Design, methods and impact of the COVID-19 pandemic

BackgroundUp to 75% of hip fracture patients never recover to their pre-fracture functional status. Supervised exercise that includes strength training can improve functional recovery after hip fracture. The role of testosterone replacement for augmenting the effects of exercise in older women after hip fracture is unknown. MethodsThe Starting Testosterone and Exercise after Hip Injury (STEP-HI) Study is a 6-month Phase 3 multicenter randomized placebo-controlled trial designed to compare supervised exercise (EX) plus 1% testosterone topical gel, with EX plus placebo gel, and with enhanced usual care (EUC). Female hip fracture patients age ≥ 65 years are being recruited from clinical centers across the United States. Participants are community dwelling and enrolled within 24 weeks after surgical repair of the fracture. The EX intervention is a center-based program of progressive resistance training. The EUC group receives a home exercise program and health education. Participants receive dietary counseling, calcium and vitamin D. The primary outcome is the Six Minute Walk Distance. Secondary outcomes include physical performance measures, self-reported function and quality of life, and dual energy x-ray absorptiometry measures of body composition and bone mineral density. ResultsEnrollment, interventions, and follow-up are ongoing. We describe the impact of the coronavirus disease 2019 pandemic on the trial, including modifications made to allow continuation of the interventions and outcome data collection using remote video and audio technology. ConclusionsResults from the STEP-HI study are expected to have important clinical and public health implications for management of the growing population of hip fracture patients.

Just How Effective and Safe Is Testosterone Therapy in Women

Although some clinicians manage bothersome low sexual desire by administering testosterone (T), no formulation specifically for women is available in

Testosterone therapy for women with low sexual desire: a position statement from the Brazilian Society of Endocrinology and Metabolism.

To summarize current evidence regarding testosterone treatment for women with low sexual desire. The Female Endocrinology and Andrology Department of the Brazilian Society of Endocrinology and Metabolism invited nine experts to review the physiology of testosterone secretion and the use, misuse, and side effects of exogenous testosterone therapy in women, based on the available literature and guidelines and statements from international societies. Low sexual desire is a common complaint in clinical practice, especially in postmenopausal women, and may negatively interfere with quality of life. Testosterone seems to exert a positive effect on sexual desire in women with sexual dysfunction, despite a small magnitude of effect, a lack of long-term safety data, and insufficient evidence to make a broad recommendation for testosterone therapy. Furthermore, there are currently no testosterone formulations approved for women by the relevant regulatory agencies in the United States, Brazil, and most other countries, and testosterone formulations approved for men are not recommended for use by women. Therefore, testosterone therapy might be considered if other strategies fail, but the risks and benefits must be discussed with the patient before prescription. Arch Endocrinol Metab. 2019;63(3):190-8.

A Randomized Placebo-Controlled Trial of Low-Dose Testosterone Therapy in Women With Anorexia Nervosa.

Anorexia nervosa (AN) is a psychiatric illness with considerable morbidity and no approved medical therapies. We have shown that relative androgen deficiency in AN is associated with greater depression and anxiety symptom severity. To determine whether low-dose testosterone therapy is an effective endocrine-targeted therapy for AN. Double-blind, randomized, placebo-controlled trial. Clinical research center. Ninety women, 18 to 45 years, with AN and free testosterone levels below the median for healthy women. Transdermal testosterone, 300 μg daily, or placebo patch for 24 weeks. Primary end point: body mass index (BMI). Secondary end points: depression symptom severity [Hamilton Depression Rating Scale (HAM-D)], anxiety symptom severity [Hamilton Anxiety Rating Scale (HAM-A)], and eating disorder psychopathology and behaviors. Mean BMI increased by 0.0 ± 1.0 kg/m2 in the testosterone group and 0.5 ± 1.1 kg/m2 in the placebo group (P = 0.03) over 24 weeks. At 4 weeks, there was a trend toward a greater decrease in HAM-D score (P = 0.09) in the testosterone vs placebo group. At 24 weeks, mean HAM-D and HAM-A scores decreased similarly in both groups [HAM-D: -2.9 ± 4.9 (testosterone) vs -3.0 ± 5.0 (placebo), P = 0.72; HAM-A: -4.5 ± 5.3 (testosterone) vs -4.3 ± 4.4 (placebo), P = 0.25]. There were no significant differences in eating disorder scores between groups. Testosterone therapy was safe and well tolerated with no increase in androgenic side effects compared with placebo. Low-dose testosterone therapy for 24 weeks was associated with less weight gain-and did not lead to sustained improvements in depression, anxiety, or disordered eating symptoms-compared with placebo in women with AN.

MON-225 A Randomized Placebo-Controlled Trial of Low-Dose Testosterone Therapy in Women with Anorexia Nervosa

Background: Anorexia nervosa is a serious psychiatric illness with significant mortality and no approved medical therapies. Comorbid affective disorders are highly prevalent, and we have shown that relative androgen deficiency in anorexia nervosa is associated with depression and anxiety symptom severity. As women with anorexia nervosa are relatively testosterone deficient, we hypothesized that physiologic testosterone therapy would improve weight, depressive and anxiety symptoms, and eating disorder symptoms and behavior. Methods: 90 women 18-45 yo with anorexia nervosa and free testosterone levels below the median for healthy young women were randomized to testosterone 300 mcg daily or placebo patch (Procter & Gamble) for 6 months. % free testosterone was measured by equilibrium dialysis and total testosterone by HTLC (Mayo Labs). Psychiatric disorders were diagnosed using the Structured Clinical Interview for DSM-IV. Depression and anxiety symptom severity were assessed [Hamilton Depression Rating Scale (HAM-D); Hamilton Anxiety Rating Scale (HAM-A)]. Eating disorder psychopathology/behaviors were assessed [Eating Disorder Examination (EDE) and Eating Disorder Inventory-2 (EDI-2)]. Primary outcome was BMI. Secondary outcomes were HAM-D, HAM-A, EDE, and EDI-2 scores. Results: Baseline characteristics, including mean testosterone levels, did not differ between the active and placebo groups. Mean age was 27±7(SD) years, BMI 18.3±1.6 kg/m2, and free testosterone 0.4±0.2 ng/dL (normal: 0.3-1.9 ng/dL). 64% of subjects met criteria for major depressive disorder and 68% for generalized anxiety disorder. Mean HAM-D score was 15±4 (moderate depression severity) and mean HAM-A score was 15±5 (mild anxiety severity). Groups did not differ in % of subjects who started/discontinued (44%) or changed psychiatric medication dose (30%) during the study. Mean increase in serum free testosterone was 0.9±0.9 ng/dL in the testosterone group. Mean BMI increased by 0.02±1.01 kg/m2 in the active, and 0.5±1.1 kg/m2 in the placebo, group (p=0.03) over 6 months. At 4 weeks, there was a trend toward a greater decrease in mean depression (-1.6±2.8 vs -0.7±3.0, p=0.09 by HAM-D), but not anxiety, severity score in the testosterone vs. placebo group. At 6 months, mean HAM-D and HAM-A scores decreased similarly in both groups [HAM-D -2.9±4.9 (testosterone) vs -3±5 (placebo), p=0.72; HAM-A -4.5±5.3 (testosterone) vs -4.3±4.4 (placebo), p=0.25]. There were no significant differences in EDE or EDI-2 scores between groups. Testosterone was well-tolerated with no difference between groups in androgenic side effects. Conclusion: Contrary to what was hypothesized, low-dose testosterone therapy for 6 months in women with anorexia nervosa resulted in less weight gain, and did not lead to sustained improvements in depression, anxiety, or disordered eating symptoms, relative to placebo.

Effects of testosterone therapy for women: a systematic review and meta-analysis protocol

BackgroundTestosterone therapy for women is in widespread use, primarily in the form of compounded preparations and off-label use of formulations for men. The benefits and risks of such therapy remain uncertain. This review will identify and evaluate studies that have examined the effects of testosterone therapy for women on a range of outcomes including sexual function, cardiovascular events, metabolic parameters, musculoskeletal health, wellbeing, cancer events, androgenic effects and withdrawal rates.MethodsStudies meeting our pre-determined inclusion criteria will be identified through searches in Ovid MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL) and Web of Science. Assessing a range of outcomes, we will assess the risk-of-bias of relevant studies and draw conclusions about the strength of evidence for benefits and risks of testosterone therapy for each outcome.DiscussionThis comprehensive systematic review with meta-analysis will provide the foundation for the development of evidence-based clinical practice guidelines that will address benefits and risks of testosterone therapy, when treatment might be appropriate or inappropriate, areas of clinical uncertainty and the basis for assessment and monitoring of patients.Systematic review registrationPROSPERO registration number: CRD42018104073

Testosterone therapy for women with poor ovarian response undergoing IVF: a meta-analysis of randomized controlled trials.

The aim of the present systematic review and meta-analysis was to summarize evidence on the effectiveness of testosterone supplementation for poor ovarian responders (POR) on IVF outcomes. The primary outcome was live birth rate (LBR); secondary outcomes were clinical pregnancy rate (CPR), miscarriage rate (MR), total and MII oocytes, and total embryos. This meta-analysis of randomized controlled trials (RCTs) evaluates the effects of testosterone administration before/during COS compared with a control group in patients defined as POR. The primary outcome was live birth rate (LBR); secondary outcomes were clinical pregnancy rate (CPR), miscarriage rate (MR), total and MII oocytes, and total embryos. Pooled results were expressed as risk ratio (RR) or mean differences (MD) with 95% confidence interval (95% CI). Sources of heterogeneity were investigated through sensitivity and subgroup analysis. All analyses were performed by using the random-effects model. Women receiving testosterone showed higher LBR (RR 2.29, 95% CI 1.31-4.01, p = 0.004), CPR (RR 2.32, 95% CI 1.47-3.64, p = 0.0003), total oocytes (MD = 1.28 [95% CI 0.83, 1.73], p < 0.00001), MII oocytes (MD = 0.96 [95% CI 0.28, 1.65], p = 0.006), and total embryos (MD = 1.17 [95% CI 0.67, 1.67], p < 0.00001) in comparison to controls, with no difference in MR (p = ns). Sensitivity and subgroup analysis did not provide statistical changes to the pooled results. Testosterone therapy seems promising to improve the success at IVF in POR patients. Further RCTs with rigorous methodology and inclusion criteria are still mandatory.

The Safety of Testosterone Therapy in Women

Hypoactive sexual desire disorder (HSDD), a subset of female sexual dysfunction, causes personal distress for surgically and naturally postmenopausal and premenopausal women. HSDD has a multifactorial etiology, including psychosocial factors such as relationship issues and medical factors such as medications, chronic illnesses, and hormonal effects. Although no androgen therapies for female sexual dysfunction are currently approved for use in Canada, clinical trials support the efficacy and short-term safety of testosterone therapy for HSDD. We review the scientific evidence for the safety of testosterone therapy for HSDD.

Progress on the largest and longest controlled study of testosterone therapy in women

Progress on the largest and longest controlled study of testosterone therapy in women

Beneficial effects of testosterone therapy in women measured by the validated Menopause Rating Scale (MRS)

Objectives This study was designed to measure the beneficial effects of continuous testosterone therapy, delivered by subcutaneous implant, in the relief of somatic, psychological and urogenital symptoms in both pre- and post-menopausal patients, utilizing the validated Health Related Quality of Life (HRQOL), Menopause Rating Scale (MRS). Study design 300 pre- and post-menopausal women with symptoms of relative androgen deficiency, were asked to self-administer the 11-item MRS, at baseline and 3 months after their first insertion of the subcutaneous testosterone implant. Baseline hormone measurements, menopausal status and BMI, were assessed to determine correlation with symptoms and clinical outcome. Main outcome measurements Changes related to therapy were determined. Total MRS scores as well as psychological, somatic and urogenital subscale scores were compared prior to therapy and following testosterone implant therapy. Results Pre-menopausal and post-menopausal females reported similar hormone deficiency symptoms. Both groups demonstrated similar improvement in total score, as well as psychological, somatic and urogenital subscale scores with testosterone therapy. Better effect was noted in women with more severe complaints. Higher doses of testosterone correlated with greater improvement in symptoms. Conclusion Continuous testosterone alone, delivered by subcutaneous implant, was effective for the relief of hormone deficiency symptoms in both pre- and post-menopausal patients. The validated, HRQOL questionnaire, Menopause Rating Scale (MRS), proved a valuable tool in the measurement of the beneficial effects of testosterone therapy in both cohorts.

Safety of Physiological Testosterone Therapy in Women: Lessons from Female-to-Male Transsexuals (FMT) Treated with Pharmacological Testosterone Therapy

The safety of long-term physiological doses of testosterone (T) therapy in women with sexual dysfunction is a contentious issue, in part, because of fear of adverse effects, such as breast cancer, vascular disease, and excessive virilization. This unsubstantiated fear has hampered progress in treating women with sexual dysfunction using T therapy in physiological doses to achieve circulating levels in the normal range. To examine evidence derived from studies in female-to-male transsexuals (FMT) treated with supraphysiological (pharmacological) doses of T for long periods of time with no apparent major adverse effects. A comprehensive literature search of relevant articles published between 1980 and 2010 pertaining to the topic of T in FMTs was performed using PubMed. The following key words were used: female-to-male transsexuals; testosterone; virilization; gender re-assignment; and androgen therapy in women. Relevant articles were retrieved, reviewed, and the information was analyzed and evaluated for study methodology and major findings. Data from peer-reviewed publications were critically analyzed and the information was summarized. The data from the studies reported in the literature to date strongly suggest that treatment of FMTs with supra-physiological doses of T had minimal adverse effects. No increase in mortality, breast cancer, vascular disease, or other major health problems were reported. No significant serious adverse effects were reported in FMTs treated with pharmacological doses of T. In light of the findings with supraphysiological doses of T, we suggest that treatment with T at doses producing physiological levels in women with sexual dysfunction are expected to produce limited and minimal adverse effects.