Should we be prescribing testosterone to perimenopausal and menopausal women? A guide to prescribing testosterone for women in primary care

EVIDENCE TO SUPPORT TESTOSTERONE USE IN WOMEN

Numerous studies have shown that adding testosterone to hormonal therapy can improve sexual function and general wellbeing among women during their menopause. A recent systematic review and meta-analysis of testosterone treatment in women has provided robust support for a trial of testosterone in women when clinically indicated. In postmenopausal women, testosterone supplementation improved several domains of sexual response, including sexual desire, pleasure, arousal, orgasm, and self-image.⁴

It has also been shown to have additional benefits including the improvement of urogenital, psychological, and somatic symptoms, an increase in bone density, and enhancement of cognitive performance when combined with oestrogen as part of HRT. Many women notice that taking testosterone improves their mood, concentration, motivation, and energy levels.

A significant problem with prescribing testosterone is that there are currently no available licensed preparations for women in the UK. The BMS has recently released some guidance on testosterone prescribing which suggests some of the products that can be used and their doses (Box 1).⁵ General Medical Council guidance on the prescription of unlicensed medication should be consulted when prescribing. It is important to ensure that women are adequately oestrogenised before adding in testosterone; this is usually the case when they are no longer experiencing vasomotor symptoms or vaginal dryness.

The normal range of testosterone is difficult to define as most of the available tests do not provide the accuracy or precision required when testing the low serum concentrations in women. As most testosterone is protein bound to sex hormone-binding globulin (SHBG), there is only a small circulating free fraction, which is difficult to measure reliably. The level of bioavailable testosterone can be estimated using Free Androgen Index (FAI). BMS guidance suggests that in a symptomatic woman with an FAI of <1%, a trial of testosterone supplementation could be considered.⁵

It can sometimes take several weeks or even months for a woman to notice the beneficial effects of testosterone. If they have not noticed an improvement after 6 months, then it is unlikely to be beneficial.

Current BMS guidance suggests that, when monitoring women who are using testosterone, the level of FAI should be maintained at <5% but that clinical improvement in symptoms is more important than aiming for a specific level on treatment (Box 2).⁵

An international task force of experts from leading medical societies, brought together by the International Menopause Society, has recently produced a Global Position Statement to provide clear guidance regarding the prescribing and measurement of testosterone for female testosterone therapy, as well as advice on testosterone prescribing practices that have the potential to be ineffectual or cause harm. They concluded that testosterone can be effective at improving sexual wellbeing for postmenopausal women with hypoactive sexual desire dysfunction (HSDD). Recognised benefits included improved sexual desire, arousal, orgasm, and pleasure, together with reduced concerns and distress about sex.⁶ They advise measuring testosterone levels at baseline and at 3–6 weeks after treatment initiation. Patients should be monitored for their clinical response to treatment and assessed for signs of androgen excess, with a serum total testosterone level every 6 months to screen for overuse. There should be cessation after 6 months if there has been no response to treatment.⁶

SAFETY OF TESTOSTERONE

Testosterone appears to be safe when used transdermally and in low doses. There are little long-term safety data on the use of testosterone in menopausal women beyond 2 years. What is available is reassuring in that transdermal testosterone is not associated with an increase in blood pressure and has no adverse effects on lipid profile.⁶ Evidence shows that there are also no changes in renal function, liver function, or blood cell indices with transdermal testosterone in women.⁷ There is no increased risk of breast cancer in the short term⁶ and it does not appear to stimulate the endometrium.⁸ It is currently not known how safe it is to prescribe testosterone to women who have breast cancer, and this would be a decision for a secondary care menopause service, on a case-by-case basis and after discussion with an oncologist.

Side effects can occasionally occur including acne and increased hair growth at the site of application, but increase in facial hair, alopoecia, or voice deepening does not occur if testosterone levels are kept within the female physiological range.⁴

There is an urgent need to ensure gender equality in effectively managing women with sexual dysfunction related to hypoandrogenic states. Having a licensed testosterone preparation available for women would certainly be a step in the right direction.

As most menopausal women can be managed in primary care, the new BMS guidance will aid GPs to feel confident to initiate testosterone, if appropriate, or to continue prescriptions that have been started in specialist clinics.