Perimenopause and post menopause hormonal treatment

Transdermal (TD) oestradiol is usually prescribed first-line as the risk of thrombotic effects is lower with this route. Oral oestradiol undergoes metabolism in the liver where clotting factors are produced. 

A progestogen is also needed for women if they have a uterus and are on any oestrogen-containing HRT, as it is used to protect the lining of the uterus (endometrium). This is because oestrogen can cause endometrial proliferation and endometrial cancer. It is important that this is clearly explained to all women starting HRT. Note: the risk of endometrial cancer is increased in women with overweight or obesity, or diabetes (independent of HRT). 

Most menopausal women, can use TD, body identical HRT containing oestradiol to help with their symptoms. If indicated, oral micronised progesterone (body identical) is commonly used. 

Treatment regimens 

Perimenopausal women (with a uterus) usually take their HRT sequentially i.e. an oestrogen-containing product for 28 days of their menstrual cycle and the progestogen-containing product on days 14-28 of their cycle. For example, 200mg micronised progesterone orally on days 14-28, which allows a monthly menstrual bleed.  

Post menopausal women take their HRT continuously as oestradiol (plus progestogen if they have a uterus). For example, 100mg micronised progesterone every day, usually at night. 

Women with a complex medical history e.g. CV disease, endometriosis, migraine, history of cancers need to discuss their options with a clinician with specialist menopause training. 

Common problems with HRT 

Breakthrough bleeding can happen in the first 3-6 months after starting HRT and after changing the dose or formulation, women should be reassured that this is not unusual. However, any post-menopausal unexpected bleeding after 6 months of continuous HRT needs to be investigated.  

Women will need further assessment and an internal ultrasound. If there are no cancer findings, the endometrium is ≤ 4mm, and no additional risk factors the dose of micronised progesterone can be increased to 200mg at night (See Useful Resources for further information). 

Other symptoms, such as mood changes, breast tenderness, or bloating may be improved by trying a different dose/route of oestradiol or switching the progestogen, if symptoms are severe or do not improve after at least 3 months. Micronised progesterone capsules are sometimes used intravaginally (off-licence) in those who cannot tolerate progesterone orally.   

Oestradiol blood levels may need to be checked if the woman has tried different TD formulations (gels/patches/spray) at maximum doses and is still experiencing symptoms. The aim is to achieve physiological levels to help minimise symptoms and improve QoL.   

Oestradiol levels should be between 250 picomol/L and 1000 picomol/L. Low oestradiol levels may be due to poor skin absorption, which can occur in about 25% of those using TD HRT. Some factors that affect absorption include site of application, skin temperature, hydration, and epidermal thickness. 

Contraception and HRT 

The College of Sexual & Reproductive Healthcare (CoSRH) states that women aged under 50 years should use contraception for two years after their final MP, and those aged over 50 need to use contraception for at least a year. The progestogen-only pill (POP) can be used with HRT but it does not give enough endometrial protection to be used as HRT. However, the IUS containing levonorgestrel can be used for both contraception and the progestogen part of HRT. 

Managing GSM 

Vaginal and bladder symptoms tend to worsen with time unless treated, impacting future health and wellbeing. Vaginal oestradiol/oestriol can be used and as systemic absorption is minimal there are few contraindications.   

Some individuals (about 20%) may need both systemic HRT and vaginal oestrogen, if they have GSM despite optimal HRT. Tablets and creams should be used nightly for 2 weeks (3 weeks for pessary and gel) and then twice weekly as maintenance.   

This can be continued long-term as symptoms frequently recur on stopping. Since absorption is minimal, progestogen is not required. Additional, non-hormonal lubricants and moisturisers can also be used. 

Advice for women starting HRT

• Allow 3-6 months on treatment, and after dose or formulation changes to see if symptoms/adverse effects improve, unless intolerable
• Progesterone is needed to protect the lining of the uterus
• Report any unexpected bleeding after taking continuous HRT for over 6 months
• Take progesterone capsules at bed-time, ideally 2 hours after food. It has a sedative effect, so may help sleep
• Despite dose optimisation, TD oestradiol may not be effective in 25% of women due to absorption problems. Ask for a blood test to check oestradiol levels
• They may need a different dose/formulation to other women they know
• Individualised therapy can take many months to achieve success. Only change one thing at a time as more likely to know what might be helping

Testosterone the missing piece of the puzzle?   

Testosterone is also a female hormone (about a tenth of the levels found in men) that declines with age, produced by the ovaries and adrenal glands. Even with oestradiol optimised, some women still experience symptoms. 

Currently, RCT data are only available for use in reduced libido (hypoactive sexual desire Disorder - HSDD). Yet, observational studies also report women having improvements in energy, mood, brain function and MSK health. 

A blood test is needed to check baseline levels, before starting treatment if levels are suboptimal in women with symptoms. Unfortunately, most licensed products are designed for men so need to be used at much lower doses. Testosterone can be prescribed through the NHS but depending on local formularies, specialist advice may be required e.g. GP with specialist interest consults with a hospital specialist.