Menopause—guidance on management and prescribing HRT

Primary Care Women's Health Forum


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The following section, with the exception of Ovarian Cancer is based on NICE Guideline 23 (NG23)
Menopause: diagnosis and management

Diagnosis

  • Diagnosis can be made without laboratory tests in otherwise healthy women aged over 45 years with appropriate symptoms:
    • peri-menopause based on vasomotor symptoms and infrequent periods
    • menopause in women who have:
      • not had a period for at least 12 months and are not using hormonal contraception
    • in women without a uterus displaying vasomotor symptoms
  • Consider using a follicle-stimulating hormone (FSH) test to diagnose menopause only:
    • in women aged 40–45 years with menopausal symptoms, including a change in their menstrual cycle
    • in women aged under 40 years in whom menopause is suspected
  • If possible, test FSH day 2–5 of cycle
  • Two FSH levels over 30 mIU/ml taken 6 weeks apart in women using hormonal contraception rendering them amenorrhoeic (intrauterine system, progestogen-only pill, etonogestrel implant), can be used to determine when contraception can be stopped (after a further 12 months in women over 50 years)
    • do not test FSH levels in women using combined hormonal contraception or depot medroxyprogesterone acetate
  • Some women may have normal levels of FSH during the menopausal transition, so this should not exclude peri-menopause as a cause of their symptoms

Vasomotor symptoms

  • Offer women hormone replacement therapy (HRT) after discussing with them the short-term (up to 5 years) and longer-term benefits and risks
  • Offer a choice of preparations as follows:
    • oestrogen and progestogen to women with a uterus
    • oestrogen alone to women without a uterus
  • Do not offer selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), or clonidine as first-line treatment for vasomotor symptoms alone. Consider testosterone supplementation for menopausal women with low sexual desire if HRT alone is not effective

Urogenital atrophy

  • Vaginal oestrogen can be given to women with urogenital atrophy (including those on systemic HRT) and continued for as long as needed to relieve symptoms
  • If vaginal oestrogen does not relieve symptoms of urogenital atrophy, consider increasing the dose after seeking advice from a healthcare professional with expertise in menopause. Vaginal moisturisers and lubricants can be used alone or in addition to vaginal oestrogen
  • There is no need for monitoring of endometrial thickness during treatment of urogenital atrophy with vaginal oestrogens. But advise women they should report unscheduled vaginal bleeding promptly

Venous thromboembolism

  • The risk of venous thromboembolism (VTE) is increased (relative risk=2) by oral HRT compared with baseline population risk
  • The risk associated with transdermal HRT given at standard therapeutic doses (under 50 µg/24 h) does not appear to be greater than baseline population risk
  • Consider transdermal rather than oral HRT for menopausal women who are at increased risk of VTE, including those with a body mass index (BMI) over 30
  • Refer menopausal women at high risk of VTE (e.g. those with a strong family history of VTE or a hereditary thrombophilia) to a haematologist or local specialist/GP with Special Interest in the menopause for assessment, before considering HRT

Cardiovascular disease

  • HRT does not increase coronary heart disease risk when started in women aged under 60 years, and does not affect the risk of dying from cardiovascular disease
  • The presence of cardiovascular risk factors is not a contraindication to HRT as long as they are optimally managed
  • The baseline risk of coronary heart disease and stroke for women around menopausal age varies according to their personal cardiovascular risk factors
  • HRT with oestrogen alone is associated with no, or reduced, risk of coronary heart disease if started before the age of 60
  • HRT with oestrogen and progestogen is associated with little or no increase in the risk of coronary heart disease if started before the age of 60
  • Taking oral oestrogen (but not transdermal under 50 µg/24 h) is associated with a small increase in the risk of stroke, but the baseline population risk of stroke in women aged under 60 years is very low, so the increased risk is non significant

Type 2 diabetes

  • Taking HRT (either orally or transdermally) is not associated with an increased risk of developing type 2 diabetes
  • In women with diabetes, HRT is not generally associated with an adverse effect on blood glucose control

Osteoporosis

  • Give women advice on bone health and discuss any risk factors for osteoporosis
  • The baseline population risk of fragility fracture for women around menopausal age in the UK is low and varies according to their personal and familial risk factors
  • Risk of fragility fracture is decreased while taking HRT but returns to normal for age and personal risk factors when treatment stops, although may persist for a while in women who take HRT for longer

Loss of muscle mass and strength

  • There is limited evidence suggesting that HRT may improve muscle mass and strength, which otherwise tends to decrease after the menopause. Muscle mass and strength is also maintained through daily activities and weight-bearing exercise

Breast cancer

  • HRT does not affect the risk of dying from breast cancer
  • The baseline risk of breast cancer for women around menopausal age varies according to the presence of underlying familial and environmental risk factors
  • HRT with oestrogen alone is associated with little or no increase in the risk of breast cancer
  • HRT with oestrogen and progestogen can be associated with an increase in the risk of breast cancer, however any increase in risk of breast cancer is related to treatment duration and reduces after stopping HRT

Ovarian cancer (not covered by NG23)

  • A 2015 meta-analysis of 52 epidemiological studies has shown an increased risk of ovarian cancer with oestrogen-only and combined HRT. While this study provides evidence of an association between HRT use and some tumour subtypes, it provides insufficient evidence to claim that HRT causes ovarian cancer
  • When counselling patients, it is important to discuss these findings in terms of absolute risk
  • With 5 years of HRT use, there could be 1 additional ovarian cancer per 1000 users and 1 additional death per 1700 users among women of all ages
  • A better way of framing it is to point out that, after 5 years of HRT there is only a 0.1% increase in ovarian cancer and less than 0.6% additional deaths

Premature ovarian insufficiency

  • In women with premature ovarian insufficiency (menopause under 40 years) it is important to start hormonal treatment either with HRT or a combined hormonal contraceptive
  • This treatment should be continued until at least the age of natural menopause (unless contraindicated) to protect against the increased risk of dementia, cognitive decline, cardiovascular disease, and osteoporosis seen in these women
  • HRT has a negligible effect on blood pressure and beneficial effects on metabolic parameters, when compared with a combined oral contraceptive
  • Both HRT and combined oral contraceptives offer bone protection
  • HRT is not a contraceptive
  • Consider referring women with premature ovarian insufficiency to healthcare professionals who have the relevant experience to help them manage all aspects of physical and psychosocial health related to their condition

Review each treatment for menopausal symptoms at 3 months to assess efficacy and tolerability. Annually thereafter unless there are clinical indications for an earlier review (such as treatment ineffectiveness, side effects or adverse effects).

Table 1: Progestogens
Synthetic Progestogens Features Natural Progestogens Features
C19 testosterone derivatives
Norethisterone, norgestrel, levonorgestrel Better cycle control
Androgenic (good for libido)
Unfavourable effect on lipids
Micronised progesterone Fewer progestogenic side effects
No androgenic or glucocorticoid activity
No impact on lipids
Less effective cycle control
C21 testosterone derivatives
Medroxyprogesterone acetate Can be added to oral or transdermal oestrogen
(Androgenic so may be good for libido)
Unfavourable effect on lipids
Dydrogesterone Non Androgenic
Not available as single preparation
IUS=levonorgestrel Replace after 5 years as per FSRH guidance
There is minimal systemic absorbtion
IUS=intrauterine system; FSRH= Faculty of Sexual and Reproductive Healthcare.

Figure 1: Flow chart of HRT prescribing

Flow chart of HRT prescribing
Table 2: Possible routes of medication
HRT Tablets* Second line* Transdermal*
Sequential preparations
For patients with:
  • intact uterus
  • perimenopausal—under 1 year or amenorrhoea
Continuous combined
Bleed free HRT use if:
  • amenorrhoeic>1 year
  • >54 years
  • >3 years on sequential HRT
  • Can be useful if:
    • bloating on oestrogen
    • poor libido
    • endometriosis
Unopposed oestrogen
Post hysterectomy
Topical vaginal oestrogen
Progestogen adjunct to topical oestrogen if no hysterectomy
* Use lowest dose to control symptoms.
HRT=homone replacement therapy.
See BNF for a full list of medications to use; there are alternatives available.

The Primary Care Women's Health Forum (PCWHF) is a charity focused on improving the education of healthcare professionals in the area of women’s health. Membership is free and the forum provides tips and useful guides free of charge, along with educational webinars and meetings. To find out more or become a member, head to www.pcwhf.co.uk

References

full guideline available from…
www.pcwhf.co.uk/documents/pcwhf_menopause_guidelines_2016.pdf

Primary Care Women's Health Forum. Menopause—guidance on management and prescribing HRT for GPs based on NICE guidance 2015. April 2016.


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