Should Women Receive Androgen Replacement Therapy, and If So, How?

From Clinical Endocrinology
Susan R. Davis

Posted: 03/01/2010; Clin Endocrinol. 2010;72(2):149-150.

Abstract

The available clinical evidence supports efficacy of testosterone therapy for the treatment of postmenopausal women with hypoactive sexual desire disorder (HSDD) who have undergone a comprehensive clinical evaluation.
Although few preparations designed to deliver an appropriate dose of testosterone for women are available, use of testosterone by women for the management of HSDD is widespread.
Issues that continue to simulate debate in this therapeutic area include whether HSDD is a condition that merits pharmacotherapy, how effective is such treatment and whether testosterone therapy is safe. Hence the question, should women receive androgen replacement therapy, and if so, how?

Introduction
Circulating levels of testosterone and the major pre-androgens, dehydroepiandrosterone (DHEA), DHEA sulfate (DHEAS) and androstenedione decline with age in women, with the maximal rate of decline occurring in the premenopausal years (Fig. 1).
However, there is no diagnostic lower limit for any of these circulating steroids which can be used to classify a woman as androgen deficient.
Thus the use of testosterone therapy for women is not based on an established link between symptoms and biochemistry, but rather clinical evidence that exogenous testosterone improves specific parameters of sexual function in women.

Figure 1.
Relationship between age and individual androgens for the reference group.
The most commonly reported sexual problems in women relate to sexual desire and interest, pleasure and global satisfaction.
The Diagnostic and Statistical Manual for Mental Disorders, Fourth Edition provides major classifications for female sexual dysfunction (FSD): hypoactive sexual desire disorder (HSDD), sexual arousal disorder, orgasmic disorder, dyspareunia and other (such as aversion).
HSDD is diagnosed when a woman presents with loss of sexual desire in association with personal distress.
The prevalence of HSDD amongst postmenopausal women is in the order of 9 to 14%, with no differences between natural in surgically menopausal women.

Most studies evaluating the efficacy of testosterone for the treatment of FSD have required women to fulfil the diagnostic criteria of HSDD.
The controversies regarding the use of testosterone to treat HSDD appear to be firstly whether this is a condition that merits pharmacological intervention and secondly whether testosterone as a pharmacological intervention is sufficiently effective and safe.
The views expressed in this manuscript differ from the more conservative recommendations by the Endocrine Society Clinical practice guidelines published in 2006 which stated that 'Although there is evidence for short-term efficacy of testosterone in selected populations, such as surgically menopausal women, we recommend against the generalized use of testosterone by women because the indications are inadequate and evidence of safety in long-term studies is lacking'
Since that time several large studies of the efficacy and safety of testosterone and DHEA use in women which have been of longer duration have been published providing more outcome data.

Treatment Options
Presently there is a lack of approved preparations of testosterone specifically suitable for use in women. Use of preparations designed to deliver a dose of testosterone to men cannot be condoned.

In several countries, testosterone therapy is commonly initiated with testosterone pellets implanted under local anaesthetic subcutaneously. Most commonly a dose of 50 mg is used.[43] These implants remain effective for periods of 4 to 6 months. Repeat implantation should not be undertaken without confirmation that total testosterone corrected for SHBG, or free testosterone has fallen back into the lower quartile of the normal female range.

Testosterone transdermal patches have been shown to be effective and have a good short-term safety profile when used by naturally or surgically postmenopausal women with and without concurrent oestrogen therapy.[11,42] The Intrinsa® patch which delivers 300 μg of testosterone daily has been approved for use by surgically menopausal women using concurrent systemic oestrogen therapy in European Union countries. A transdermal testosterone cream for women, marketed as Androfeme1%®, is available in Australia[28] and testosterone gels for women and a transdermal spray are in development.

Various pharmacists prepare testosterone for buccal administration in the form of troches, or as creams, but there are no published pharmacokinetic or safety data or efficacy studies to validate this method of administration.

Some clinicians undertake a clinical trial of intramuscular injections of testosterone esters 50 to 100 mg. This may or may not result in a clinical response over 1–2 weeks or more. A positive response supports the initiation of longer term therapy. However, as peak levels are supraphysiological, testosterone esters should not be considered a long-term treatment option.

Another agent which can be conceived as having androgenic effects (in addition to having properties as an oestrogen and a progestin) is tibolone. In a dose of 2·5 mg daily, it improves sexual function in postmenopausal women.[44] DHEA therapy has not been covered in this article. There are little data to support the use of DHEA for the treatment of sexual dysfunction and safety data are limited.

Conclusion
Taken together, the available clinical evidence supports the efficacy of testosterone therapy for the treatment of postmenopausal women with HSDD who have undergone a comprehensive clinical evaluation. Data for use in women in their late reproductive years remain limited. Available data do not demonstrate serious safety concerns; however, further studies are required to determine the long-term safety of testosterone in women.

http://www.medscape.com/viewarticle/716443_6