Female sexual dysfunction: the place for testosterone

Low libido, or a reduced desire for sex, can be seen as normal and should be considered problematic only when it causes distress. Various terms are used to describe low libido, including hypoactive sexual desire disorder (HSDD) which is used by the Royal Australian and New Zealand College of Obstetricians and Gynaecologists.

Patients may find it helpful to understand more about female sexual desire and arousal and there are some good resources available from:

• The Jean Hailes women’s health website.
• The book “Where Did My Libido Go?” by Dr Rosie King.
• The Australasian Menopause Society (AMS) information sheet on Sexual Difficulties in the Menopause.

Libido may be a sensitive topic and patients can be reluctant to raise it. Be proactive and ask: “Are you concerned about difficulties with sexual activity?”

The physiology of sexual desire and interest is complex and individual; hormones are only one component. Factors such as relationship issues, health comorbidities (e.g. diabetes), previous sexual or emotional abuse, and body image issues can impact on a woman’s desire for sex. It is important to elicit non-hormonal factors contributing to low libido, as these are targets for therapy.

Estrogen levels are directly related to libido, as evidenced by studies showing a correlation between reduced estrogen and reduced sexual function.² This is particularly relevant during the menopausal transition, when declining estrogen causes vaginal dryness and can make intercourse uncomfortable. Other menopause-related sleep and mood issues may also contribute to reduced libido and overall energy.

Testosterone is less directly associated with libido. Overall testosterone levels decline with age starting from the mid-20s, although ovaries continue to produce androgens during menopause. Available testosterone, as measured by the free androgen index, remains stable throughout menopause.

Testosterone is more likely to contribute to low libido in women who have had bilateral oophorectomy, who can experience an almost 50% reduction in free testosterone, which likely contributes to reduced libido.²

It is important to note also that the assay used to measure testosterone was designed for men and may not be accurate for women.

Therapies for reduced libido target the multifactorial causes and must be individualised to best target the key contributing factors for each patient. In short, targets for therapy are:

• Treatment of genitourinary symptoms of menopause (GSM) to minimise dyspareunia (see here for guidance)
• Estrogen replacement with MHT (ensuring that the risk-benefit ratio stacks up; see our MedCase on MHT)
• Treatment of anxiety or depression if present.
• Relationship counselling.
• Cognitive-behavioural therapy or other psychological intervention from an appropriately qualified therapist (see Sexual Therapy NZ website).

There is currently no testosterone treatment specifically for women that has been approved by a regulatory authority (such as MedSafe or the FDA), though the off-label use of male testosterone formulations is not uncommon in clinical practice.

It should be a considered 3rd or 4th line therapy option, after other relevant contributing factors have been addressed.

Until recently there were little data on the efficacy of testosterone in women, but a 2019 meta-analysis has provided a useful summary of the available evidence allowing better guidance for clinicians.² The authors evaluated 36 randomised controlled trials in over 8,000 patients using both oral and transdermal formulations. Overall, the findings suggest that testosterone is effective for the treatment of low libido in post-menopausal women.

No serious adverse effects were reported in the analysis.² However, studies were of short duration and no long-term safety data is available.  There was a formulation-dependent increase in cardiovascular risk; oral testosterone therapy was associated with negative effects on cholesterol and is not recommended.  In contrast, non-oral (transdermal) testosterone did not affect lipids over a 12-week period and is preferred for use in women.

Common concerns associated with testosterone use relate to the hirsutism, acne and weight gain. Though these were reported in the studies, they did not lead to treatment discontinuation. Patients should be encouraged to balance the risks and benefits of treatment when deciding whether to continue.

A diagnosis of low libido or HSDD relies on clinical rather than laboratory findings. However, testing total testosterone pre-treatment is useful to exclude high androgen states where testosterone therapy should be avoided.

During therapy, it is important to monitor total testosterone to ensure levels remain within the normal range for premenopausal women. The total testosterone blood test is funded; check with your local laboratory for the normal range as it may vary by assay type.

Note that patients may be aware of a test for active testosterone called the Free Androgen Index (FAI) [also called sex hormone binding globulin or SHBG]. Testing active testosterone is more accurate that measuring total testosterone, since testosterone is highly protein-bound. However, this test is not funded in New Zealand and it is not necessary to guide treatment.

Other useful pre-investigation investigations are lipids, given the risk of hyperlipidaemia with oral preparations, and a pregnancy test; testosterone can have a virilising effect on the foetus.³  Confirm that the woman is not pregnant before starting treatment.

A transdermal formulation is recommended to avoid adverse lipid changes. The most common formulation prescribed by women’s health specialists is AndroFeme cream, which is not registered for use in New Zealand but is approved for use in women in Western Australia. This is not a compounded testosterone cream (which has no safety or regulation data), and information on prescribing it can be found here. A suggested starting dose is 0.5cm applied to the skin daily. Monitor for local skin reactions and adjust the dose based on testosterone levels, which can be measured 3-monthly.

Of note, the only registered topical testosterone in New Zealand is a long-acting testosterone patch³ (brand name: Androderm®), which is indicated for male use; it is used off-label in females. This patch is used rarely in practice.

This MedCase was created in 2020 by Dr Vicki Mount, General Practitioner, MBChB, DipPaeds, with expert review by Dr Stella Milsom, Reproductive Endocrinologist, MBChB, Dip Obs, FRACP.