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The National Institute for Health and Care Excellence has published recommendations on diagnosis and treatment of menopause, including around the benefits and risk of hormone replacement therapy (HRT).
Prof. Adam Balen, Chair of the British Fertility Society, and Professor of Reproductive Medicine and Surgery, Leeds Centre for Reproductive Medicine, said:
“This guideline is an extremely important document which covers the full range of symptoms experienced by women who have gone through the menopause and also for those who may have experienced an early menopause, under the age of 40. Women going through the menopause may experience a range of symptoms which can be very debilitating and have a major influence on quality of life. The British Fertility Society wholeheartedly endorses and supports this essential guideline which will be of benefit to every woman and the healthcare professionals who care for them.”
Prof. Paul Pharoah, Professor of Cancer Epidemiology, University of Cambridge, said:
(Commenting on the breast cancer and HRT aspect)
“My first comment is that Table 3 that clinicians are supposed to use to ‘explain to women around the age of natural menopause that…’ is very hard to understand and has numbers that are contradictory. In addition, the wording of 1.5.11 in the summary guideline is rather odd. E.g. ‘HRT with estrogen and progestogen can be associated with an increase in the incidence of breast cancer’. Does this mean it is associated or that in some women it is and in others it is not?
“I don’t have access to the full guideline (only the short version) in order to understand how their figures have been derived.
“In my view the best evidence for the effect of estrogen only HRT and estrogen + progestagen HRT comes from the Women’s Health Initiative (WHI). The numbers from the observational studies are not reliable because of possible biases.
“Of 1000 50 year old women in the UK, 23 would be expected to be diagnosed with breast cancer before they are 60 years old.
“If 1000 50 year old women took the estrogen + progestagen combined HRT for five years, then 28 would be expected to be diagnosed with breast cancer before they are 60 (an increase of 5 per 1000).
“Taking estrogen only HRT has a minimal effect on breast cancer risk.
“The statement in the summary guideline that ‘any increase in risk is related to treatment duration and reduces after stopping HRT’ is not very helpful. It ought to be specified how much it is reduced by.
“In the WHI trial the relative risk fell sharply after stopping HRT but did not fall back to baseline after 8 years. Based on my evaluation of those data: of 1000 55 year old women who have never taken HRT, 25 will get breast cancer before they are 65 (a slightly higher ten year risk than a 50 year old). If those 1000 women had taken estrogen + progestagen HRT for five years from age 50 and then stopped, then 34 would get breast cancer by age 65 (an increase of 9 per 1000).”
Dr Richard Quinton, Consultant Endocrinologist, Newcastle upon Tyne Hospitals NHS Foundation Trust, Senior Lecturer, Institute of Genetic Medicine, Newcastle University, and Member of the Society for Endocrinology, said:
“NICE has taken a sensible and pragmatic position. They have clearly engaged with relevant stakeholders, including ‘expert’ patients, and have applied logic to areas where the evidence basis is thin. Crucially, they have referred to absolute rather than relative risks of adverse events. Finally, they have been open about several key areas for which more data are required.
“I just have minor criticisms as follows:
‘1.4.8 Consider testosterone supplementation for menopausal women with low sexual desire if HRT alone is not effective.’
This seems a little odd as there is no licensed product. A simpler thing is to switch to HRT containing a more androgenic progestogen such as Norethisterone acetate.
“‘1.4.15 Explain to women that the efficacy and safety of unregulated compounded bioidentical hormones are unknown.’
Quite true, but they should also be advised that regulated bioidentical hormone products do exist, such as Estradiol/estradiol valerate and Utrogestan (=micronized progesterone).
“‘1.4.20 Refer women to a healthcare professional with expertise in menopause…’
They could be more explicit in sign-posting women to the most easily-accessible expertise in this area, i.e. the same local community sexual health experts that they probably visited earlier in life for contraceptive advice.
“‘Venous thromboembolism
1.5.1 Explain to women that:
It’s a shame that they didn’t cast their net slightly wider in terms of evidence basis. For instance, the Charing Cross Registry of male-to-female trans-sexuals (who take high-dose estrogen lifelong) found an 8-fold higher risk of VTE with Conjugated equine estrogens (Premarin) than with either oral or transdermal estradiol products.
“‘1.6.6 Offer sex steroid replacement with a choice of HRT or a combined hormonal contraceptive to women with premature ovarian insufficiency, unless contraindicated (for example, in women with hormone-sensitive cancer).’
They should have mentioned that any women with premature ovarian insufficiency (POI) should be screened for Turner syndrome with karyotype, due to the multiple other problems and diseases encountered by adult Turner women. Also the rationale for prescribing an oral contraceptive agent (rather than HRT) to women with infertility rather escapes me. Women with POI tend to get their vasomotor symptoms and vaginal dryness back again for one-week-in-4, corresponding to the pill-free week. Also, combined oral contraceptive pills are based around the estrogen-analog Ethinylestradiol, rather than actual estrogen, so it’s a bit like treating hypogonadal men with nandrolone, rather than native testosterone replacement.”
‘Menopause: diagnosis and management. NICE guideline: short version. November 2015’ published by NICE on Thursday 12 November 2015.
Declared interests
Prof. Adam Balen declares that he has no relevant interests.
Prof. Paul Pharoah: “I have no conflicts of interest to declare.”
Dr Richard Quinton: “I have no conflicts of interest. In the past 3 years I have received a single pharma speaker’s fee from Amgen (which I don’t think is active in the area of menopause & HRT) to give a talk on vitamin D to Sheffield renal Physicians.”