Long-term data for safety and benefit of testosterone therapy in women are lacking, but such data are required before long-term use of testosterone can be recommended. Similarly, safety data for the use of testosterone in nonestrogen replaced postmenopausal women are lacking and no recommendation for its use can be made currently. Nor can the supplementation of T to premenopausal women be recommended until such time there exist safety and efficacy data. Unfortunately, any enduring benefit after short-term treatment, although theoreti- cally possible, is unproven. In addition, supplementing T on a temporary basis only, could have adverse effects on the couple if an improvement associated with T therapy is no longer apparent when it is withdrawn.
If despite the above, T supplementation is contemplated, careful assessment must establish absence of ongoing psychological (interpersonal, intrapersonal, contextual, and societal) and/or physical factors negatively affecting sexual inter- est and arousability. On the basis of available data, no specific testosterone regimen or dose can yet be recommended. The chosen formulation of testosterone must have pharmacokinetic data indicating that it produces blood levels within the normal premenopausal range. Achieving physiological free testosterone levels by transdermal delivery appears to be the best approach.
Contraindications to testosterone therapy include androgenic alopecia, seborrhea, or acne, hirsutism as well as a history of polycystic ovary syndrome, and estrogen depletion. Oral methyl testosterone therapy is contraindicated in women with hyperlipidemia or liver dysfunction. Regular follow up is both clinical—inspection of skin and hair for seborrhea, acne, hirsutism, and alopecia—and biochemical through monitoring of free/bioavailable testosterone and SHBG, keeping these values within the normal range for premenopausal women. Of note, methyl-T is not included in the usual assays for T. Possibly, the target level for older women should be even lower but this remains unclear. Lipid profile and glucose tolerance are also monitored. The current rec- ommendation is to prescribe only for 12 months owing to lack of long-term safety data (92).
Tibolone is a synthetic steroid with tissue selective estrogenic, progestogenic, and androgenic actions. In use in Europe for more than 10 years, tibolone pro- vides some relief from vasomotor symptoms (93), estrogen agonist activity on the vagina (94) and bone (95), but not on the endometrium (96). Tibilone was thought not to have estrogen agonist activity on breast tissue; but a recent, albeit nonrandomized but very large study of postmenopausal hormonal therapy showed a similar increase in breast cancer in women receiving tibolone and those receiving various combinations of estrogen and progestins (97). The typical ( presumed beneficial) estrogenic effects on lipids are not seen (98), but it is of note that tibolone does not promote (unwanted) coagulation (96). Prospective randomized trials comparing tibolone to placebo or to various formulations of estrogen and progestin therapy have been done. Although in most (99 – 101) but not all (102), there was significant improvement in sexual desire/interest in the women receiving tibolone; no study focused on sexually dysfunctional women. Recruitment centered on vasomotor symptoms or bone density. Studies in postmenopausal women with loss of arousability and therefore of sexual interest are needed.
A Biopsychosocial Approach to Therapy
There is a general expectation that modulation of the neurotransmitters involved in sexual arousability and desire from hormonal and nonhormonal therapy, will become available. As there are psychological and interpersonal sequelae of medical disruption of the sexual response, benefit beyond placebo may only be seen if a holistic biopsychosexual treatment approach is used. For instance, loss of arousability and desire in breast cancer survivors is strongly linked to ovarian failure induced by chemotherapy (103). These women report that their former means of sexual stimulation to arousal are no longer effective. Couples describe how local (vaginal) nonsystemic estrogen can allow painless but rather perfunc- tory intercourse. Most need encouragement to bring back their former sexual con- texts and stimuli that were discarded once they no longer worked. Usually, the partner needs to be heard regarding his/her feelings of rejection. Both partners need information on the role of ovarian hormones. Partial replacement of the woman’s lost ovarian androgens, rarely helps on its own.
RECOMMENDATIONS FOR CLINICAL PRACTICE
. Assessment needs to be biopsychosocial, as well sexual (Table 3.1).
. Consider predisposing, precipitating, and maintaining factors.
. Endeavor to see the couple together and separately.
. Create a model of the woman’s sexual response cycle showing the various breaks or areas of weakness.
. Interpersonal issues need to be addressed first.
. When abuse is elicited in the history, determine whether recovery has taken place. When this is not complete, defer addressing sexual issues and make appropriate referral.
. When negative outcome needs specific treatment (e.g., chronic dys- pareunia), address that in parallel with addressing the low desire. Meanwhile, normalize and encourage nonpenetrative sex.
. Psychological therapies are the mainstay of treatment and include sex therapy, sensate focus therapy, CBT, psychodynamic treatment, couple treatment, and promotion of the individual as a separate self.
. There are no firm nonhormonal pharmacological recommendations at this time. However, clinical experience and a recent study (104) suggest increased arousability to sexual cues from administering bupro- pion to nondepressed women diagnosed with hypoactive sexual desire/ interest, again in keeping with the lowering of desire if arousability is impaired.
. When arousability and accessed desire sharply declines in conjunction with a known cause of reduction of androgens (e.g., younger premeno- pausal women with loss of all ovarian function), consider investiga- tional testosterone therapy using a formulation that produces physiological as opposed to pharmacological levels. Hopefully, there will be such formulation in the near future.
. Remember safety data regarding T treatment are only short-term and
only for the estrogen replete woman. There are no data on T sup- plementation to premenopausal women whereby the achieved androgen levels have been strictly physiological.
. Analogue assays for free-T are currently unreliable—but total T alone is insufficient owing to SHBG bound T being relatively unavailable to the tissues. Thus, modifying T formulations designed for men is fraught with difficulties due to lack of reliable laboratory monitoring.
. If and when hormonal and pharmacological treatments become avail- able, a biopsychosocial approach to treatment will still be needed. Secondary dysfunctions, changed expectations, adaptations to the low arousability, and disinterest will have occurred. These may negate any potential benefit.
There are many reasons why women are sexual. A broad normative range in sexual desire exists between women and across life stages. The extreme import- ance of sexual arousability—used here to mean the factors influencing the mind’s information processing of the sexual stimulation—directs the assessment and management of distress resulting from disinterest in sex. The subject is larger and more complex than a “hypoactive sexual desire disorder.” Desire, as in sexual thoughts and fantasies is helpful, but is neither sufficient nor essential for on-going healthy sexual interest.