Hormone Replacement Therapy

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Who should be offered HRT?

  • Peri- and postmenopausal women with symptoms attributable to the menopause.
  • Follicle-stimulating hormone (FSH) measurements are not indicated prior to HRT treatment but may be considered to diagnose menopause only in women aged 40 to 45 years with menopausal symptoms or in women under 40 in whom menopause is suspected.
  • Adopt an individualised approach at all stages of diagnosis, investigation and management of menopause.

Should first choice be oral or transdermal?

  • Oral treatment is cost-effective and is well tolerated.
  • Start with lower dose regimes and reappraise need on an annual basis. Do not change preparation before an adequate trial has been completed, as side-effects are common in the first 3 months but usually subside.
  • The risk of VTE associated with HRT is greater for oral than transdermal preparations. The risk associated with transdermal HRT given at standard therapeutic doses is no greater than baseline population risk.
  • Consider transdermal rather than oral HRT for menopausal women who are increased risk of VTE, including those with a BMI over 30kg/M².

When can bleed-free regimes be used?

  • Women who have had no periods for at least 1 year prior to starting HRT or after 2 years on a sequential regimen.

What are the contra-indications to HRT?

  • Active arterial or venous thromboembolic disease.
  • Unexplained vaginal bleeding.
  • Oestrogen-dependent tumours, eg breast, uterus.
  • Recent myocardial infarction and/or active coronary heart disease.

Risks of HRT

  • HRT does not increase cardiovascular risk when started in women aged under 60 years. Cardiovascular risk factors are not a contraindication to HRT as long as they are optimally managed.
  • Oral HRT (not transdermal) is associated with a small increase in the risk of stroke although the baseline population risk of stroke in women aged under 60 years is very low.
  • Risk of VTE is increased by oral HRT compared to baseline population. If HRT is to be used by women at increased risk of thromboembolism, use a transdermal preparation.
  • HRT with oestrogen and progestogen can be associated with an increase risk in breast cancer but any increase is related to the treatment duration and reduces on stopping HRT. HRT with oestrogen alone is associated with little or no change in the risk of breast cancer.
  • If 1000 women age 50 to 59 used combined HRT for 5 years, it is estimated that an extra 3 breast cancers will be diagnosed.
  • If HRT is commenced at a young age then the use of HRT up to age 50 does not increase breast cancer risk any more than in a woman who continues to have periods up to age 50.

General points

Discontinuing HRT

There is no clear consensus on how to discontinue HRT, and symptoms may recur regardless of whether HRT is stopped slowly or suddenly. It is not usually appropriate to start women over the age of 60 on HRT but it does not mean that those who have started it earlier need to stop it on reaching 60.

Alternatives to HRT for menopausal symptoms

  • Do not routinely offer SSRI or SNRI type drugs or clonidine as first-line treatment for vasomotor symptoms alone. There is no clear evidence for SSRI or SNRI to ease low mood in menopausal women who have not been diagnosed with depression.
  • Consider HRT to alleviate low mood that arises from the menopause
  • Relaxation therapy, mindfulness-based therapies and CBT may alleviate low mood and anxiety arising as a result of the menopause.
  • There is some evidence that isoflavones or black cohosh may relieve vasomotor symptoms but safety is uncertain and interactions with other medicines have been reported.

Atrophic vaginitis

  • Vaginal oestrogen effectively treats urogenital atrophy (including those on systemic HRT (see section 7.2). Continue treatment for a long as needed to relieve symptoms.
  • Vaginal oestrogens may be considered in women in whom systemic HRT is contra-indicated.
  • Non-hormonal options such as moisturisers and lubricants can be used alone or in addition to vaginal oestrogens.

Access to further information

For further information on issues around the menopause refer to www.menopausematters.co.uk or www.thebms.org.uk.

Table

 

HRT

TABLETS/OTHER

PATCHES

HINTS

Sequential preparations

For women with intact uterus

  • perimenopausal
  • under age 54 with less than one year amenorrhoea

Always start on lower dose

Elleste-Duet®
estradiol 1 or 2mg
norethisterone 1mg (C19)

Cyclo-progynova®
estradiol 2mg tablets and estradiol2mg/norgestrel 500 micrograms tablets

Femoston®
estradiol 1 or 2mg
dydrogesterone 10mg (C21)

Evorel® Sequi
estradiol 50 micrograms
norethisterone 170 micrograms (C19)

Femseven® Sequi
estradiol 50 micrograms  levonorgestrel 10 micrograms (C19)

Consider patches if liver disease or previous history of DVT/PE (see overleaf major caution).

Switch from C19 to C21 progestogens if PMS-like symptoms and/or androgenic side-effects*.

For persistent oestrogenic side-effects** reduce dose, change preparation or move to transdermal preparation.

Continuous combined preparations
(period-free HRT)

For women over age 54

or

more than one year since last menstrual period

or

after 2 years on sequential regime 

Always start on lower dose

Premique® Low Dose
conjugated oestrogen (equine) 300 micrograms, medroxyprogesterone acetate 1·5mg (C21)

Kliofem®
estradiol 2mg  norethisterone 1mg (C19)

Evorel® Conti
estradiol 50 micrograms norethisterone 170 micrograms (C19)

Femseven® Conti
estradiol 50 micrograms levonorgestrel 7 micrograms (C19)

Switch from C19 to C21 progestogens if PMS-like symptoms and/or androgenic side-effects*.

For persistent oestrogenic side-effects** reduce dose, change preparation or move to transdermal preparation.

If switching from a sequential regimen try to keep to same ‘type/hormones’ where possible.

Oestrogen only

For women without a uterus

Always start on lower dose

Elleste-Solo®
estradiol 1 or 2 mg

Premarin®
conjugated oestrogens (equine) 300 micrograms, 625 micrograms or 1·25mg

Evorel®
estradiol 25 or 50 or 75 or 100 micrograms
(start on 50 microgram patch then adjust to lowest effective dose)

Estraderm MX®
estradiol 25 or 50 or 75 or 100 micrograms
(start on 50 microgram patch then adjust to lowest effective dose)

Consider patches if liver disease or previous history of DVT/PE (see overleaf major caution).

For persistent oestrogenic side-effects** reduce dose, change preparation or move to transdermal preparation.

Topical oestrogen***

To relieve vaginal symptoms only

Use minimum effective amount to control symptoms

Estradiol (Vagifem®)
vaginal tablets
10 micrograms

or

Estriol
cream 0·01%

Review at 3 to 6 month intervals.

Vagifem 10 micrograms has good long-term endometrial safety data.

Progestogen

For the prevention of endometrial hyperplasia during oestrogen replacement therapy

Mirena ®
(releasing levonorgestrel 20 micrograms/24 hours) intra-uterine system

Lowest progestogenic side-effects. Potentially lowest breast cancer risk, as with oestrogen only HRT.

 *C19 (testosterone derivatives) eg norethisterone, levonorgestrel, norgestrel and C21 (progesterone derivatives) eg dydrogesterone, medroxyprogesterone. C19 progestogens may lead to bloating, mastalgia, depression, irritability and skin changes in a minority of women.

**Oestrogenic side-effects include breast tenderness, bloating, leg cramps, nausea and headaches, and usually settle within 3 months.    

*** refer to section 7.2.

Editorial Information

Last reviewed: 31 May 2017

Next review: 30 June 2018

Author(s): Obstetric and Gynaecology Review Group

Version: 7

Approved By: high-uhb.tam@nhs.net

Document Id: TAM182