In the final of our three-part miniseries, Dr Toni Hazell discusses some specific challenges that can come up with prescribing of testosterone and synthetic, bioidentical and high-dose HRT
When might you use testosterone as part of HRT?
A woman searching online for information about the menopause won’t go far before finding a recommendation that she take testosterone. Claims abound that it will increase stamina and energy levels, reduce joint pain, anxiety and brain fog, improve the mood and help women to feel younger. Contrary to popular belief, it isn’t a panacea or a fountain of youth, but a specific treatment for a specific condition (hypoactive sexual desire disorder), probably indicated in only a small number of women.
Premenopausal women produce both oestrogen and testosterone, but levels of testosterone decline gradually with age; there is no sharp drop at the time of menopause. NICE guidance advises that we might consider testosterone supplementation for women with low sexual desire associated with menopause, if HRT alone is not effective. The British Menopause Society (BMS) agrees with this and also reminds us that a biopsychosocial approach should be taken to exclude other causes. These might include relationship or psychological issues, or iatrogenic causes of low libido such as the use of some antidepressants.
A GP might consider prescribing testosterone for a woman who is significantly troubled by a low libido, after a suitable period of time on HRT at an appropriate dose and when the issues above have been excluded. Some GPs will feel comfortable starting this in primary care, others will want to refer to a menopause clinic – this decision might also be affected by any prescribing restrictions in a particular area. For women taking oral HRT, the first step should be to suggest a change to a transdermal (TD) preparation. Oral HRT increases levels of sex-hormone binding globulin (SHBG), which binds to testosterone; changing to a TD preparation may increase the amount of free testosterone, so that the woman can get more benefit from the hormones that she already has.
Anyone wishing to initiate testosterone should first read the detailed BMS guidance in the source list and follow these principles:
· Check testosterone levels first to establish a baseline.
· Make the patient aware that all UK preparations are unlicensed for women.
· Monitor bloods at three months and every 6-12 months; this is to ensure that the woman isn’t over-treated. Treatment decisions should be made based on symptoms, not blood results, which should simply remain in the physiological range for a woman.
When might you use tibolone instead of another form of HRT?
Tibolone is a synthetic form of oral HRT; it has oestrogenic, progestogenic and androgenic activity and is licensed for the treatment of symptoms of oestrogen deficiency in menopausal women (ie, at least one year after the last period), and for the prevention of osteoporosis in postmenopausal women at high risk of fractures who are intolerant of, or have a contraindication to, other preventative treatments. As with other oral forms of HRT, it comes with an increased risk of venous thromboembolism (VTE) and arterial disease, which is particularly an issue for those aged over 60 when it is started. The summary of product characteristics quotes a 1.3-3 fold increase in VTE and an approximately doubled risk of stroke, noting that while the relative increase in the risk of stroke is not dependent on age or duration of use, the overall risk will increase with age as the background risk increases. Oral HRT is generally not recommended for women who have risk factors for either venous or arterial disease, and this includes tibolone, which also has a Medicines and Healthcare products Regulatory Agency (MHRA) warning in force since 2014. This advises that the risks start to outweigh the benefits at around the age of 60, with the risks being broadly similar to conventional HRT below that age. Large studies on breast cancer risk have found that it carries a similar risk to that of oestrogen only HRT, or regimes where dydrogesterone is used as the progestogen, ie, lower than other forms of combined HRT. Specific situations in which tibolone might be useful includes those with side-effects to conventional HRT, those with a poor libido and those with endometriosis.
How would you answer a patient who asks for bioidentical HRT?
A bioidentical form of HRT is one in which the hormone is an exact duplicate of the natural hormones made in a woman’s body. Micronised progesterone, estradiol and levothyroxine are all bioidentical hormones which are regulated by the MHRA and routinely prescribed by GPs. The BMS describes these forms of HRT as regulated bioidentical HRT (rBHRT). They have some advantages over synthetic hormones, which may include less adverse effects, a lower risk of breast cancer (micronised progesterone compared to other progestogens), and possibly a lower risk of VTE.
A patient asking for bioidentical HRT may however be talking about a compounded version (cBHRT), and this is a different matter altogether. cBHRT preparations are sold in the private sector; they are often individually prepared in specialist pharmacies, which may or may not be based in the UK, and they are not evidence based or regulated by the MHRA. Some private practices who prescribe cBHRT ask patients to have expensive (and unregulated) blood and saliva tests for monitoring.
The view of the BMS and the International Menopause Society is that cBHRT is not recommended, for issues of safety and regulation; in 2017 the Advertising Standards Association ruled that clinics could not claim that cBHRT was either safer or more individualised than usual HRT. Women asking for cBHRT (or who are buying it privately) should be advised of these issues and offered usual HRT. Pointing them in the direction of some patient information on the subject may also be useful.
How would you manage a patient who arrives in your practice taking an unusually high dose of HRT?
A woman’s HRT dose might be adjusted for reasons of non-response or adverse effects, but it would usually stay within the licensed dose. Notable exceptions include women with premature ovarian insufficiency (menopause before the age of 40) who often need a higher dose, and the occasional woman who genuinely doesn’t absorb TD oestrogen. Concern has been raised in recent years about prescribing of much higher doses of HRT, usually in the private sector, and without sufficient progestogen to protect the endometrium for women who still have their uterus. This carries an increased risk of endometrial hyperplasia and malignancy. The BMS guidance on unscheduled bleeding with HRT (see sources) includes tables giving the doses of oestrogen which they consider to be low, standard and high, with advice about proportionate increases of progestogen as the oestrogen dose is increased.
The medicolegal responsibility for a prescription lies with the clinician who signs it – this does not change if it was recommended by a specialist, whether in the NHS or the private sector. It is therefore important that GPs are clear as to what they consider to be safe prescribing, and that they maintain these boundaries. There is no obligation for a GP to prescribe on behalf of a specialist, and there are many precedents where specialists in the NHS continue to prescribe higher risk medication in the long term, rather than asking the GP to do it. A request for a dose of HRT which the GP does not feel to be safe can therefore be met with a polite refusal, an explanation why, and an offer to see them for an assessment of their menopause (and to prescribe within guidelines, or refer if appropriate). If the patient is not happy with that offer, then they can continue to get their prescriptions from their private specialist in the long term. A GP who does this and is then the recipient of a complaint might want to use this statement from the BMS to defend the fact that their actions are based on concern for the patient’s safety and wellbeing. Their Local Medical Committee and Medical Defence Organisation would also back them up, if this was wanted.
Dr Toni Hazell is a GP in North London, who has a particular interest in women’s health. She is a director at the Primary Care Women’s Health Forum
