Testosterone replacement in menopausal women (Guidelines)

Presentation

Testosterone is an important female hormone. Women produce more testosterone than oestrogen physiologically. Approximately half of endogenous testosterone and precursors are derived from the ovaries and half from the adrenal glands. Testosterone levels naturally decline throughout a woman’s lifespan. Loss of testosterone is particularly profound after iatrogenic i.e. surgical and medical menopause and premature ovarian insufficiency when testosterone production decreases by more than 50%.

Testosterone contributes to libido, sexual arousal and orgasm by increasing dopamine levels in the central nervous system. Testosterone also maintains normal metabolic function, muscle and bone strength, urogenital health, mood and cognitive function.

Indication: The only evidence based clinical indication is for acquired, generalised Female Sexual Interest/Arousal Disorder (formerly HSDD) in postmenopausal women.

Testosterone deficiency in women can lead to a number of distressing sexual symptoms such as low sexual desire, arousal and orgasm. Other contributory factors which should be taken into account when assessing women with these symptoms include psychosexual, physical, iatrogenic and environmental. The patient should be in a good healthy relationship, is not experiencing sexual pain, body (including vulva and vagina) is oestrogenised and have had medication side effects, external stressors and mental health issues addressed prior to considering testosterone for low libido.

Testosterone deficiency can also contribute to a reduction in general quality of life, tiredness, depression, headaches, cognitive problems, osteoporosis and sarcopenia. However, there is insufficient research data about the effectiveness of testosterone for these indications. Clinically, many women will see an improvement in these symptoms.

Menopausal women should be prescribed HRT in the first instance (Menopause and HRT guidance). Switching to transdermal oestrogen may be more beneficial for symptom control including for low sexual desire. For those women whose oestrogen deficiency symptoms are well controlled (systemically and genitally) but continue to be distressed by low libido and low mood, insomnia, fatigue and low energy levels, or cognitive issues (brain fog, difficulty in concentrating), a trial of testosterone would be indicated.

Serum Oestradiol levels do not need to be monitored. If oestrogen deficiency symptoms are poorly controlled, refer patient to HSH Menopause Clinic or seek advice via Clinical Dialogue.

Private Menopause Specialists: There are some private providers who have been advocating testosterone for all menopausal women, commencing testosterone at the same time as commencing HRT and without monitoring. This is out with British Menopause Society and International Menopause Society recommendations.

Management

Testosterone treatment in women is supported by NICE guidance and menopause specialist advisory bodies. Current medical data shows that transdermal testosterone does not increase the risk of breast cancer, cardiovascular disease, or venous thromboembolism. It does not affect renal or liver function or blood cell indices and does not cause an increase in blood pressure.

Side effects: can include skin irritation, acne, oily skin, increased hair growth at the site of application and weight gain. The risks of increase in facial hair, alopecia, voice deepening (may be irreversible) or clitoromegaly (may be irreversible) do not occur provided the testosterone levels are kept within the female physiological range.

Monitoring: It is recommended that Total testosterone levels are checked to establish a baseline for future monitoring and to ensure levels are not in the upper range before treatment is commenced. Total testosterone levels should be rechecked 2-3 months after commencing treatment and then on an annual basis (along with annual HRT review for symptom control, risk assessment and BP monitoring) to ensure that levels remain within the female physiological range in order to minimise adverse effects. Women should be advised to omit the testosterone dose prior to their blood test as this can give a falsely high result.

Test request forms for Testosterone should indicate the reason for request is menopause and if they are on testosterone.

Note: Androstenedione (testosterone precursor from ovary) and 17-hydroxyprogesterone (from adrenal glands) levels will also be reported from labs as part of the androgen profile but only the testosterone level is required for this indication.

If testosterone levels are >1.5nmoL/L after commencing testosterone, reduce the frequency of testosterone replacement dose (eg to twice weekly) and check levels again after 3 months. It can take up to 3 months to see a clinical response. If no improvement after 6 months, treatment should be stopped. Women with low testosterone levels without symptoms do not require testosterone.

Treatment Options: There are currently no testosterone products licensed for female use in the UK. The following testosterone products, licensed for men, can be prescribed off label in female doses:

First line - Tostran® (2% testosterone gel in a canister containing 60g):
Starting dose 1 metered pump (0.5g) of gel = 10mg testosterone on alternate days. Each canister should last 240 days.
If Tostran is not available due to shortages, a non-formulary option is Testogel® 40.5mg testosterone gel in 2.5g sachets.
Starting dose 1/8 of a sachet/day = 5mg testosterone/day.
Instruction to patient: Apply tiny pea size amount (0.3g of gel) to skin daily. Each sachet should last 8 days.

Note: Testogel® 1% testosterone gel in 5g sachets containing 50mg testosterone has been withdrawn as of 31/03/22.

Note: Testogel®16.2mg/g gel pump containing 20.25mg testosterone per metered dose (1.25g of gel) is not suitable for female use due to its high concentration.

Note: AndroFeme® (1% testosterone cream in 50ml tubes). Starting dose 0.5ml/day = 5mg testosterone/day. Each tube should last 100 days. Designed for female usage. Not currently available in the NHS and is being imported from Western Australia by special license from the MHRA. Commonly prescribed by private menopause specialists in UK. If requesting NHS prescription, use Tostran 2%.

How to use the gel/cream: The testosterone gel/cream should be applied thinly to clean dry skin (lower abdomen/upper thighs/outer arms) and allowed to dry before dressing. Skin contact with partners or children should be avoided until dry and hands should be washed immediately after application. The area of application should not be washed for 2-3 hours after application. Vary site of application to avoid increased body hair at site of application. If gel/cream applied on arms, avoid applying at cubital fossa where blood will be taken for testosterone levels.

Avoid use in:

Women with upper normal or high baseline testosterone levels / FAI
Active liver disease
History of hormone sensitive breast cancers
Competitive athletes (care must be taken to ensure levels remain well with female physiological range)

Referral

Testosterone replacement for menopause may be initiated in primary care if clinician is confident to do so. Advice may be sought via Clinical Dialogue or Refer via SCI Gateway to Menopause Clinic, Highland Sexual Health

Patient information

Abbreviations

Abbreviations	Meaning
BMS	British menopause society
BSSM	British society for sexual medicine
FAI	free androgen index
HRT	Hormone replacement therapy
HSDD	hypoactive sexual desire disorder
HSH	Highland sexual health
MRHA	Medicine and healthcare products regulatory agency
NICE	National institute for health and clinical excellence
SHBG	Sex hormone binding globulin