By Dr Sonia Davison
Sue, 54 year old
Sue, a 54 year old lady, presents asking advice about lowered libido.
- Hashimoto’s thyroiditis
- Thyroxine 100mcg
- Rosuvastatin 10mg
- Estradot 50mcg
- Prometrium 100mg
originally presented 2 years ago with a 12 month history of hot flushes and night sweats, sleep disruption, irregular periods, mood instability and weight gain. She was commenced on sequential hormone therapy (MHT) initially and changed to continuous MHT as withdrawal bleeds became scant and ceased altogether. Sue has no current vasomotor symptoms, sleeps well and has no side effects on MHT.
On further questioning Sue reveals that she is lacking in energy and motivation, her mood is flat at times, and libido has gradually been diminishing after the birth of her last child, 18 years ago. Her relationship is good, with an understanding partner, and there is no vaginal dryness or urinary symptoms. Intimacy within the relationship is important to her and Sue is distressed about the change in sexual function and worried that this will have an impact on her relationship. Although there is some stress associated with work and the health of her 78 year old mother, Sue otherwise feels that her mood is stable and does not have features suggestive of anxiety or depression.
You give Sue some information about testosterone in women from the Jean Hailes website, highlighting the benefits versus risks, in addition to the Australasian Menopause Society information sheet, ‘Sexual difficulties in the menopause’, and organise the following investigations. Sue returns for review to discuss her results and her options after 2 weeks.
All within normal range: Thyroid function tests, lipid profile, fasting blood glucose, iron studies, sex hormone binding globulin (SHBG), testosterone 0.5 nmol/L (range 0.4 to 1.4), calculated free testosterone 10pmol/L (4 to 21).
You discuss with Sue that she is suitable for a trial of testosterone, and give her a script for Andro-feme 1% cream, with a starting dose of 0.5 ml, to be applied topically to the thigh daily. You ask Sue to have a blood test to check levels after 3 weeks, and then to return for review with another set of levels in 3 months.
3 weeks after starting treatment - total testosterone 0.9 nmol/L, calculated free testosterone 18 pmol/L (ranges for decade above), SHBG 28 nmol/L (18-114)
You inform Sue of this result with the advice that she may continue with her current dose of Andro-feme if she has noticed a benefit and has no side effects; you also offer her the option of doubling her current dose.
3 months after starting treatment - total testosterone 1.6 nmol/L, calculated free testosterone 33 pmol/L (ranges for decade above), SHBG 26 nmol/L (same range).
Sue returns for review and reports that the addition of testosterone has been associated with an improvement in mood, motivation and libido. Her energy levels have improved as has her wellbeing.
She has mild thigh hirsutism at the application site of Andro-feme but no other androgenic excess effects. You schedule a review in another 3 months and ask Sue to have another blood test for testosterone levels prior to her review.
Sue has hypoactive sexual desire disorder (HSDD), which is low libido associated with distress. She is postmenopausal and her oestradiol deficiency symptoms are adequately managed with her MHT.
Testosterone use in women has been associated with controversy however a recent meta-analysis of randomised controlled studies of testosterone studies in women, including over 8000 subjects, has reported improvements in various sexual function measures, including sexual desire, and a reduction in sexual distress. Adverse effects were minimal, most commonly acne and hirsutism, with no serious adverse events noted (1).
Testosterone falls with age in adult women, with peak levels around the age of 20 years, a halving of levels is seen around age 40 years, and a nadir is reached around 65 years of age (2). The aim of testosterone treatment is to replicate peak adult female levels of testosterone, i.e. total testosterone levels between 0.9 to 2.5 nmol/L. However protein binding affects the amount of ‘free’ or active testosterone, hence it is essential to measure SHBG, so that the amount of free testosterone can be calculated (= FAI, or free androgen index in some laboratories). The aim for calculated free testosterone is around 13 to 39 pmol/L, however this may differ according to laboratory, hence it is reasonable to aim for the peak adult female range for the assay available at the local laboratory. If there is a laboratory offering a ‘sensitive’ assay that is able to accurately measure testosterone at the low levels seen in women and children, it is recommended that this assay is used. Direct assays for free testosterone are not recommended for use in women, due to assay inaccuracy at the extremely low levels of free testosterone seen in women.
The blood test 3 weeks after commencing treatment is advised to ensure levels are not excessive, however women should be advised that symptom relief may take up to 3 months to become apparent. If the 3 month level is within physiological range and there is no improvement at 3 months, then it is unlikely that a benefit will be seen after this time.
A recently published consensus statement about testosterone use in women states that the only evidence based indication for testosterone is HSDD. The safety of long-term use is unknown, and it recommends only using formulations that achieve levels that approximate premenopausal physiological levels. In Australia we have the product Andro-feme 1% cream, which has pharmacokinetic and safety data in women and is formulated for female use. If testosterone products for men are used there is a higher risk of androgenic excess effects including virilisation, clitoromegaly, and voice deepening; the latter two being irreversible, hence this is not recommended. The position statement recommends against a label of HSDD if there are other factors impacting on sexual function (such as relationship issues, mental health problems such as anxiety or depression, etc), and also states that a testosterone level is not adequate to diagnose HSDD. The initial testosterone level is performed to ensure there is no pre-existing androgen excess, and the subsequent levels are aimed at ensuring side effects are minimised by maintaining levels within the female reproductive range (3).
- Islam RM et al. 2019 Safety and efficacy of testosterone for women: a systematic review and meta-analysis of randomised controlled trial data. Lancet Diabetes Endocrinol 2019; Jul 25.
- Davison S et al. 2005 Androgen Levels in Adult Females: Changes with Age, Menopause, and Oophorectomy. JCEM 90(7):3847-53
- Davis SR et al. 2019 Global Consensus Position Statement on the Use of Testosterone Therapy for Women. Climacteric, Menopause, JCEM, Maturitas, J Sexual Medicine. 2019; Sep 2
Content created October 2019