Medical Abstract:

Originally Published: November 2010

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

Introduction. 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.

Aim. 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.

Methods. 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.

Main Outcome Measures. Data from peer-reviewed publications were critically analyzed and the information was summarized.

Results. 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.

Conclusions. No significant serious adverse effects were reported in FMTs treated with pharmacological [normal] doses of T [Testosterone]. In light of the findings with supraphysiological [above normal] doses of T, we suggest that treatment with T at doses producing physiological [normal] levels in women with sexual dysfunction are expected to produce limited and minimal adverse effects. [21]

Medical Abstract:

Originally Published: July 2009

Approved Hormonal Treatments for HSDD: An Unmet Medical Need

Introduction. Despite a high prevalence of hypoactive sexual desire disorder (HSDD), no medical treatment is available in the United States for this condition.

Aim. To identify the current prescribing pattern of off-label testosterone use in treating HSDD.

Main Outcome Measures. Quantitation of Intercontinental Marketing Services (IMS) prescription data to identify testosterone prescriptions written for women and a summary of response to queries to opinion leaders and practicing physicians.

Methods. Interviews and an opinion poll of gynecologists and family medicine physicians on current medical treatment of HSDD.

Results. The IMS prescription review showed that: two million testosterone prescriptions were written for women in 2006 and 2007-many physicians have prescribed compounded testosterone. Based on a summary of the physicians' survey: on average, patients of all ages, but particularly menopausal women, have at least moderate awareness of HSDD. More than 80% of physicians believe there is a need or great need for a Food and Drug Administration- (FDA) approved HSDD treatment. Ninety percent of physicians surveyed would prescribe an approved HSDD product over currently prescribed therapy.

Conclusions. In the context of increased regulatory scrutiny, increasing off-label use of testosterone, formulation and dosing issues, increased patient awareness of FSD and HSDD, and overall favorable physician sentiment, the completion of the LibiGel® clinical development program and an FDA approval will meet the demand for the first safe and effective FDA-approved treatment of HSDD in postmenopausal women. [20]

Medical Abstract:

Originally Published: June 20, 2009

Role of testosterone in the treatment of hypoactive sexual desire disorder.

Hypoactive sexual desire disorder (HSDD) is a common clinical problem that may have a very negative impact on a woman's quality of life. Diagnosis and treatment is challenging, as one must keep in mind the complex web of factors influencing sexual functioning alone or in concert. Data suggest that androgens are significant independent factors affecting sexual desire, sexual activity and satisfaction, as well as other components of women's health such as mood and energy. For decades, physicians used various androgen preparations to improve sexual function in women, based on the results of smaller clinical trials and personal clinical observations when taking care of patients. Today, there is substantial body of evidence from randomized placebo-controlled trials that low-dose testosterone treatment is efficacious in women with HSDD who have an established cause of androgen deficiency such as surgical menopause. Recent data support the hypotheses that androgens may also be beneficial in naturally menopausal women or in premenopausal women with low circulating testosterone levels and a decrease in satisfying sexual activity. No single testosterone level has been found to be predictive for low female sexual function, even though women suffering from HSDD commonly have low testosterone levels. The most frequently reported side effects of testosterone treatment are mild hirsutism or acne. Long-term safety is not yet established. Several clinical trials are in progress to further investigate potential benefits and risks of androgen treatment in women with sexual dysfunction. [13]

Medical Abstract:

Originally Published: May 30, 2009

The role of testosterone in the management of hypoactive sexual desire disorder in postmenopausal women.

At least 16 million women over the age of 50 currently experience low sexual desire, with approximately 4 million women exhibiting hypoactive sexual desire disorder (HSDD). Although early research established that testosterone therapy improves sexual desire in postmenopausal women, safer and more efficacious administration routes were explored. Large randomized, double-blinded placebo-controlled studies demonstrate that transdermal testosterone improves sexual function and activity in postmenopausal women with HSDD. Large multi-center Phase III trials further confirm the positive effects of the testosterone patch in the treatment of HSDD. More recent studies are exploring the utility of testosterone gels. Based upon data from two recent clinical relevance studies, physicians can be reassured that postmenopausal women with HSDD report a meaningful benefit with testosterone therapy, and further, women will only continue therapy if they experience a meaningful benefit. Although most trials combined testosterone with estrogen/progesterone therapy, the recent APHRODITE trial examined testosterone alone, showing increased sexual desire with mild adverse events. Concerns regarding the long-term safety profile of transdermal testosterone must be addressed before the FDA will approve a testosterone product for women. Although some fear an increased risk of breast cancer with exogenous [applied to skin] testosterone administration, recent studies support the idea that androgens can play a role in suppressing the proliferative effects of estrogen and progesterone. Long-term safety data is now being collected and analyzed and Phase III trials focusing on long-term risks are underway. In the meantime, transdermal testosterone appears to be a safe and effective therapy for postmenopausal women with HSDD. [14]

Medical Abstract:

Originally Published: May 20, 2009

Safety of testosterone use in women.

Female sexual desire appears to be in part androgen dependent, which has lead to the use of testosterone in women for low libido. Despite this benefit, the long-term safety of testosterone as a hormone replacement or therapy has not been well established. Side effects of testosterone therapy include mild and reversible acne and hirsuitism, as well as changes to the lipid profile with oral, but not transdermal testosterone. Short-term studies, up to 2 years, have shown that for serum plasma [blood] testosterone levels at the upper portion or slightly above the reference range for reproductive-aged women, testosterone does not increase the risk of hepatotoxicity, endometrial hyperplasia, or behavioral hostility. No adverse cardiovascular effects including changes in blood pressure, blood viscosity, arterial vascular reactivity, hypercoagulable states, and polycythemia have been shown. Data is mixed with outcomes of breast cancer risk, with some experimental studies suggesting a decrease in estrogen-induced breast epithelial proliferation with low dose testosterone. Additionally, models of superphysiologic [elevated] testosterone levels, such as polycystic ovarian disease, have not shown an increased risk of breast cancer. As with all hormone therapy in postmenopausal women, testosterone therapy should be individualized and requires that each woman weigh the risk and benefits. Nevertheless, only long-term safety studies will provide conclusive evidence as to testosterone safety in women. [15]

Medical Abstract:

Originally Published: April 30, 2009

The safety of 52 weeks [1 year] of oral DHEA therapy for postmenopausal women.

OBJECTIVE: The aim of this study was to evaluate the safety of 52 weeks of DHEA 50mg daily oral dose given to postmenopausal women with low libido to improve sexual function.

METHOD: 93 postmenopausal women were enrolled in a 52-week randomised, double-blind, placebo-controlled trial and received either DHEA 50mg or placebo (PL) daily. The effects of DHEA versus placebo on lipid profile, insulin-glucose homeostasis and the endomentrium were assessed over 52 weeks.

RESULTS: Oral DHEA, 50mg/day, was not associated with any effects on blood lipids or insulin resistance. The pattern of breakthrough bleeding did not substantially differ between the DHEA and PL groups and no significant adverse endometrial effects were apparent.

CONCLUSIONS: The use of 50mg oral DHEA did not significantly alter lipid profile, insulin sensitivity or adversely affect the endometrium in postmenopausal women. [10]