Menopause – Guidance

on management and
prescribing HRT for GPs:
Based on NICE guidance 2015 and recent updates
WORDS BY DR IMOGEN SHAW, GPSI GYNAECOLOGY

INCLUDED IN THIS GUIDANCE:

1. A summary of the 2015 NICE guidance and other relevant studies
2. Oestrogens and progestogens used in HRT
3. A flow chart to use as a guide in choosing the appropriate treatment
• Remember that all women are different, and this is a guide only; treatment must be individualised.
There is a considerable variation in the individual’s response to different types and routes of oestrogen
for symptom control.
4. Possible medications to use - these are the drugs frequently used by the author; alternatives are available.

This resource was supported by an unrestricted educational grant from Viatris. Viatris has no editorial control over the content.
Date of creation September 2020.
Menopause – Guidance on management and prescribing HRT for GPs:
Based on NICE guidance 2015 and recent updates

1. SUMMARY 2015 NICE GUIDANCE: MANAGEMENT OF THE MENOPAUSE

Diagnosis Vasomotor symptoms

Diagnosis can be made without laboratory tests • Offer women HRT after discussing with them the
in otherwise healthy women aged over short-term (up to 5 years) and longer-term benefits
45 years with appropriate symptoms: and risks. Offer a choice of preparations as follows:
• Perimenopause based on vasomotor symptoms • Oestrogen and progestogen to women with a uterus
and irregular periods. 
 • Oestrogen alone to women without a uterus.
• Menopause in women who have: Do not offer selective serotonin reuptake inhibitors
∙ Not had a period for at least 12 months and (SSRIs), serotonin and norepinephrine reuptake
are not using hormonal contraception. Or, inhibitors (SNRIs) or clonidine as first-line treatment
∙ Symptoms in women without a uterus. for vasomotor symptoms.
Consider testosterone supplementation for menopausal
women with low sexual desire if HRT alone is not sufficient.
Consider using an FSH test to diagnose
menopause only:
• in women aged 40 to 45 years with possible Genitourinary syndrome
menopausal symptoms, including a change in
their menstrual cycle.
of menopause
• in women aged under 40 years in whom Vaginal oestrogen can be given to women with
menopause is suspected. urogenital atrophy (including those on systemic
• if possible, test day 2-5 of the cycle. HRT) and continued for as long as needed to relieve
• 2 FSH levels over 30mIU/ml taken 6 weeks apart symptoms. Treatment should be started early
in women with amenorrhoea using hormonal before irreversible changes have occurred.
contraception can be used to determine when • If vaginal oestrogen does not relieve symptoms
contraception can be stopped (after a further of urogenital atrophy, consider increasing
1 year in women over 50 years, 2 years in those the dose beyond the licensed twice-weekly
under 50 years). dose after seeking advice from a healthcare
• Some women may have normal levels of FSH professional with expertise in menopause.
during the menopausal transition, so this should Vaginal moisturisers and lubricants can be used
not exclude the perimenopause as a cause of alone or in addition to vaginal oestrogen.
their symptoms. • There is no need for monitoring of endometrial
thickness during the treatment of urogenital
atrophy with vaginal oestrogens. However, advise
women they should report unscheduled vaginal
bleeding promptly.

For more resources visit: www.pcwhf.co.uk 2

This guidance was compiled by the PCWHF and was correct at the time of going to press. The PCWHF will undertake annual reviews of this guidance to ensure
it remains in line with best practice. The next review is due in November 2021. The guidance is for use by healthcare professionals only. The guidance has been
compiled by Dr Imogen Shaw for The Primary Care Women’s Health Forum and views expressed do not necessarily represent those of individuals or partners.
Declaration of interests are available at www.abpi.org.uk/our-ethics/disclosure-uk/. For further information, please contact [email protected]
DECLARATION: This resource was supported by an unrestricted educational grant from Viatris. Viatris has no editorial control over the content.
Menopause – Guidance on management and prescribing HRT for GPs:
Based on NICE guidance 2015 and recent updates

1. SUMMARY 2015 NICE GUIDANCE: MANAGEMENT OF THE MENOPAUSE

Venous thromboembolism • HRT with oestrogen alone is associated with no,

or reduced, risk of coronary heart disease.
The risk of venous thromboembolism (VTE) • HRT with oestrogen and progestogen is
is increased by oral HRT compared with baseline associated with little or no increase in the
population risk (RR =2). risk of coronary heart disease.
• The risk of VTE associated with HRT is more • Taking oral oestrogen (but not transdermal under
significant for oral than transdermal preparations. 50mcg/24hr) is associated with a small increase
• The risk associated with transdermal HRT given in the risk of stroke, but the baseline population
at standard therapeutic doses (<50mcg) is no risk of stroke in women aged under 60 years is
greater than the baseline population risk. very low, so the increased risk is non-significant.
∙ Consider transdermal rather than oral HRT for
menopausal women who are at increased risk of The all-cause mortality in women aged 50–59 years
VTE, including those with a BMI over 30 kg/m2. taking HRT on the two Woman’s Health Institute
∙ Consider referring menopausal women at (WHI1) randomised trials during the intervention
high risk of VTE (for example, those with a phase was significantly reduced, and this reduction
strong family history of VTE or a hereditary in mortality was still present at an 18-year follow up.
thrombophilia) to a haematologist for
assessment before considering HRT.
Type 2 diabetes
Cardiovascular disease Taking HRT (either orally or transdermally)
is not associated with an increased risk of
• HRT does not increase coronary heart developing type 2 diabetes.
disease risk when started in women aged In women with diabetes, HRT is not associated
under 60 years and does not affect the with an adverse effect on blood glucose control.
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.

For more resources visit: www.pcwhf.co.uk 3

This guidance was compiled by the PCWHF and was correct at the time of going to press. The PCWHF will undertake annual reviews of this guidance to ensure
it remains in line with best practice. The next review is due in November 2021. The guidance is for use by healthcare professionals only. The guidance has been
compiled by Dr Imogen Shaw for The Primary Care Women’s Health Forum and views expressed do not necessarily represent those of individuals or partners.
Declaration of interests are available at www.abpi.org.uk/our-ethics/disclosure-uk/. For further information, please contact [email protected]
DECLARATION: This resource was supported by an unrestricted educational grant from Viatris. Viatris has no editorial control over the content.
Menopause – Guidance on management and prescribing HRT for GPs:
Based on NICE guidance 2015 and recent updates

1. SUMMARY 2015 NICE GUIDANCE: MANAGEMENT OF THE MENOPAUSE

Osteoporosis Breast cancer

Give women advice on bone health and discuss The baseline risk of breast cancer for women around
any risk factors for osteoporosis. menopausal age varies according to the presence of
• The baseline population risk of fragility fracture underlying familial and environmental risk factors.
for women around menopausal age in the UK is There is still no evidence of any increase in
low and varies according to their personal and mortality from breast cancer in women taking HRT.
familial risk factors. NICE stated that:
• Risk of fragility fracture is decreased while • HRT with oestrogen alone is associated with little
taking HRT but increases once treatment stops, or no increase in the risk of breast cancer.
although benefits may persist for a while in • HRT with oestrogen and progestogen can be
women who take HRT for longer. associated with an increase in the risk of breast
HRT is the only treatment that gives protection cancer; however, any increase in the risk of
against all fractures, even in women with normal breast cancer is related to treatment duration
bone density. and reduces after stopping HRT.
Women who have undergone an early
menopause, either natural or surgical, should be NICE guidance was based on a review of studies
prescribed HRT and advised to continue until at meeting the GRADE criteria, including the largest
least the normal age of the menopause. Women RCT the Woman’s Health Institute (WHI) study.
with established osteoporosis aged under 60y,
especially with menopausal symptoms, should be • This study suggested that if 1000 women used
given HRT to improve their bone density. HRT for 5 years, there would be 4 extra cases of
breast cancer with combined HRT use, and 4 fewer
cases with oestrogen-only use, on a baseline risk
Loss of muscle mass and strength of 15 cases per 1000 women over 5 years.
• Women who had not used HRT prior to the
There is limited evidence suggesting that HRT study showed no increase in breast cancer with
may maintain muscle mass and strength, which combined HRT for 5 years, but a higher risk than
otherwise tends to decrease after the menopause. never users with over 5 years of treatment.
Muscle mass and strength is also maintained
through daily activities and weight-bearing exercise.

For more resources visit: www.pcwhf.co.uk 4

This guidance was compiled by the PCWHF and was correct at the time of going to press. The PCWHF will undertake annual reviews of this guidance to ensure
it remains in line with best practice. The next review is due in November 2021. The guidance is for use by healthcare professionals only. The guidance has been
compiled by Dr Imogen Shaw for The Primary Care Women’s Health Forum and views expressed do not necessarily represent those of individuals or partners.
Declaration of interests are available at www.abpi.org.uk/our-ethics/disclosure-uk/. For further information, please contact [email protected]
DECLARATION: This resource was supported by an unrestricted educational grant from Viatris. Viatris has no editorial control over the content.
Menopause – Guidance on management and prescribing HRT for GPs:
Based on NICE guidance 2015 and recent updates

1. SUMMARY 2015 NICE GUIDANCE: MANAGEMENT OF THE MENOPAUSE

A meta-analysis of all available epidemiologic of oestrogen, with micronised progesterone.

evidence on the association between HRT This is now considered the progestogen of
use and breast cancer risk was published choice by most experts, as it is thought that
in The Lancet in August 2019. transdermal 17-beta-estradiol and micronised
The meta-analysis concluded: progesterone may be associated with lower
• Similar to the WHI, combined HRT regimens were breast cancer risk than conjugated oestrogens
associated with excess breast cancer risk. An excess and medroxyprogesterone acetate.
risk was also seen with oestrogen-only regimens,
unlike the reduction in risk seen in the WHI. This meta-analysis has revived concerns amongst
• Breast cancer risk increased after a year of healthcare professionals regarding the association
use of all forms of systemic HRT and continued between HRT and breast cancer. In response the
to increase with duration of use after that. BMS, IMS, and RCOG issued a joint statement:
• The authors of the study calculated that for ‘The meta-analysis provides important additional
women of average weight, 5 years of HRT use information on the risks of breast cancer, but it needs
starting at age 50 years would increase their to be considered in the context of the benefits of HRT
20-year risk of breast cancer (between the in treating vasomotor symptoms, improving sleep
ages of 50 and 69 years) by approximately: and quality of life for symptomatic women, and the
• 1 in every 50 users of oestrogen prevention of bone loss.
plus daily progestogen. The findings from the meta-analysis are in keeping
• 1 in every 70 users of oestrogen with the NICE guidance observational data on breast
plus intermittent progestogen. cancer risk, and discussions should also include
• 1 in every 200 users of oestrogen-only regimens. findings from the WHI randomised trials and E3N
observational studies which found no increased
risk of breast cancer over five years with the use
There were significant limitations of oestradiol and micronised progesterone.
in this meta-analysis2:
• It included only observational studies, mainly An 18-year long-term follow-up study of the WHI
composed of the Million Women Study. This study randomised trials published in JAMA in 2020
has been criticised for methodological flaws. concluded that use of CEE alone was significantly
associated with lower breast cancer incidence and
• The majority of women included in the analysis mortality, whereas the use of CEE plus MPA was
were using conjugated oestrogens and associated with a higher breast cancer incidence, but
medroxyprogesterone acetate, not comparable no significant difference in breast cancer mortality.’
with current HRT regimens using lower doses,
different types and routes of administration

For more resources visit: www.pcwhf.co.uk 5

This guidance was compiled by the PCWHF and was correct at the time of going to press. The PCWHF will undertake annual reviews of this guidance to ensure
it remains in line with best practice. The next review is due in November 2021. The guidance is for use by healthcare professionals only. The guidance has been
compiled by Dr Imogen Shaw for The Primary Care Women’s Health Forum and views expressed do not necessarily represent those of individuals or partners.
Declaration of interests are available at www.abpi.org.uk/our-ethics/disclosure-uk/. For further information, please contact [email protected]
DECLARATION: This resource was supported by an unrestricted educational grant from Viatris. Viatris has no editorial control over the content.
Menopause – Guidance on management and prescribing HRT for GPs:
Based on NICE guidance 2015 and recent updates

1. SUMMARY 2015 NICE GUIDANCE: MANAGEMENT OF THE MENOPAUSE

Ovarian cancer Premature ovarian insufficiency

A 2015 meta-analysis of 52 epidemiological studies In women with premature ovarian insufficiency
has shown an increased risk of ovarian cancer with (menopause under 40 years), it is essential to start
oestrogen-only and combined HRT. Whilst this hormonal treatment either with HRT or a combined
study provides evidence of an association between hormonal contraceptive.
HRT use and some tumour subtypes, it provides This treatment should be continued until at least the
insufficient evidence to claim that HRT causes age of natural menopause (unless contraindicated)
ovarian cancer. to protect against the increased risk of dementia,
When counselling patients, it is essential to discuss cognitive decline, cardiovascular disease and
these findings in terms of absolute risk. osteoporosis seen in these women.
With 5 years of HRT use, there could be 1 additional • HRT has a negligible effect on blood pressure and
ovarian cancer per 1000 users and 1 additional beneficial effects on metabolic parameters when
death per 1700 users among women of all ages. 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 events).

For more resources visit: www.pcwhf.co.uk 6

This guidance was compiled by the PCWHF and was correct at the time of going to press. The PCWHF will undertake annual reviews of this guidance to ensure
it remains in line with best practice. The next review is due in November 2021. The guidance is for use by healthcare professionals only. The guidance has been
compiled by Dr Imogen Shaw for The Primary Care Women’s Health Forum and views expressed do not necessarily represent those of individuals or partners.
Declaration of interests are available at www.abpi.org.uk/our-ethics/disclosure-uk/. For further information, please contact [email protected]
DECLARATION: This resource was supported by an unrestricted educational grant from Viatris. Viatris has no editorial control over the content.
Menopause – Guidance on management and prescribing HRT for GPs:
Based on NICE guidance 2015 and recent updates

2.OESTROGENS AND PROGESTOGENS

All routes of oestrogen administration are equally effective for symptom relief and bone protection,
but their metabolic effects differ.

• Oral oestrogen increases sex hormone binding • In women who are still experiencing some
globulin (SHBG) levels which can result in lower periods, a cyclical progestogen regime is
free testosterone concentrations, a benefit if required in order to regulate the cycles,
women are noticing postmenopausal hirsutism. encouraging a bleed around the end of each
• Transdermal preparations can be started at a month. Cyclical oral formulations contain older
low dose such as Estradiol 25 µg patch, or one progestogens which protect the endometrium
measure of Estradiol gel and titrated up until but may have progestogenic side effects.
symptoms are alleviated. If symptoms are still • For perimenopausal women, micronised
present after 1 month, an increase to 37.5 µg, progesterone 200 mg a day can be used for
then 50 µg (patch or gel) is associated with 14 days of each month. In women who are
fewer side effects such as breast tenderness and more than a year post-last period or have used
vaginal bleeding, and also keeps risks minimised. a cyclical preparation for 2 to 3 years this can
• The increased VTE risk seen with oral be transferred to a continuous regime using
preparations is not found using transdermal micronised progesterone 100 mg daily, which
preparations under 50mcg estradiol gel. should keep women amenorrhoeic.

• Most women find a standard dose of a 50µg • Micronised progesterone or dydrogesterone

patch or two measures of estradiol gel are should be the first choices of progestogen as
adequate for symptom relief; the only exception they appear to be safer for the cardiovascular
is younger women either after oophorectomy or system, having neutral effect on lipids and
with premature ovarian insufficiency who often coagulation, and a lower risk of breast cancer.
require higher doses of estradiol.

For more resources visit: www.pcwhf.co.uk 7

This guidance was compiled by the PCWHF and was correct at the time of going to press. The PCWHF will undertake annual reviews of this guidance to ensure
it remains in line with best practice. The next review is due in November 2021. The guidance is for use by healthcare professionals only. The guidance has been
compiled by Dr Imogen Shaw for The Primary Care Women’s Health Forum and views expressed do not necessarily represent those of individuals or partners.
Declaration of interests are available at www.abpi.org.uk/our-ethics/disclosure-uk/. For further information, please contact [email protected]
DECLARATION: This resource was supported by an unrestricted educational grant from Viatris. Viatris has no editorial control over the content.
Menopause – Guidance on management and prescribing HRT for GPs:
Based on NICE guidance 2015 and recent updates

2.OESTROGENS AND PROGESTOGENS

TYPE OF PROGESTOGEN GOOD FOR WATCH OUT FOR PRESCRIBED AS

SYNTHETIC: C19 TESTOSTERONE DERIVATIVES
Norethisterone Cycle control Some degree of estrogenic E2/Net fixed combined
Androgenic – good for libido effect caution if VTE risk ++ tablet/patch
or as stand alone
Levonorgestrel Cycle control Androgenic effects 52mg LNG IUS
(acne, mood) Or
As IUS Low systemic absorption PMS In combined patch
Excellent contraception
Good for HMB
SYNTHETIC: C21 PROGESTERONE DERIVATIVES
Medroxyprogesterone acetate Cycle control Caution if VTE risk + SCHRT – E2 plus
10-20mg cyclically
CCHRT-
E2 plus 5mg conti
Or fixed dose in oral
Dydrogesterone Non-androgenic so good Only available with Oral fixed dose
if PMS type side effects oral oestrogen Sequential (including
low dose) or combined
Natural progesterone: Fewer progestogenic Less effective cycle control Sequential –
Micronised progesterone side effects 200mg cyclically
No androgenic or Take at night as Or
glucocorticoid activity may cause sedation
Continuous
No impact on lipids 100mg daily

Table 1: Progestogens currently licenced for use in the UK as part of combined HRT3
PROGESTOGEN OESTROGENIC ANTI-OESTRO- ANDROGENIC ANTI-ANDRO- GLUCOCORTI- ANTIMINERALO-
GENIC GENIC COID CORTICOID
Norethisterone      
Levonorgestrel/
Norgestrel (including      
intrauterine devices)
Progesterone      
Medroxyprogesterone
     
acetate
Dydrogesterone      

For more resources visit: www.pcwhf.co.uk 8

This guidance was compiled by the PCWHF and was correct at the time of going to press. The PCWHF will undertake annual reviews of this guidance to ensure
it remains in line with best practice. The next review is due in November 2021. The guidance is for use by healthcare professionals only. The guidance has been
compiled by Dr Imogen Shaw for The Primary Care Women’s Health Forum and views expressed do not necessarily represent those of individuals or partners.
Declaration of interests are available at www.abpi.org.uk/our-ethics/disclosure-uk/. For further information, please contact [email protected]
DECLARATION: This resource was supported by an unrestricted educational grant from Viatris. Viatris has no editorial control over the content.
Menopause – Guidance on management and prescribing HRT for GPs:
Based on NICE guidance 2015 and recent updates

3. FLOWCHART FOR HRT PRESCRIBING

Menopausal HRT

Vaginal sx. only Uterus Intact Post Hysterectomy

LMP < 1 year LMP > 1 year

Oral sequential Transdermal E.

Vaginal E. lubricants combined E. & P. Oral E.
& moisturisers Oral continuous
Patch sequential Tibolone
combined E. & P.
combined E. & P.
Patch continuous
Transdermal/oral E.
combined E. & P.
+ IUS or oral P.
Transdermal/oral E. +
Estradiol valerate &
IUS or oral P.
dienogest COC –
if low risk and Tibolone
contraception needed
(COC rules apply)

Non-hormonal Clonidine Venlafaxine

treatment Gabapentin

For more resources visit: www.pcwhf.co.uk 9

This guidance was compiled by the PCWHF and was correct at the time of going to press. The PCWHF will undertake annual reviews of this guidance to ensure
it remains in line with best practice. The next review is due in November 2021. The guidance is for use by healthcare professionals only. The guidance has been
compiled by Dr Imogen Shaw for The Primary Care Women’s Health Forum and views expressed do not necessarily represent those of individuals or partners.
Declaration of interests are available at www.abpi.org.uk/our-ethics/disclosure-uk/. For further information, please contact [email protected]
DECLARATION: This resource was supported by an unrestricted educational grant from Viatris. Viatris has no editorial control over the content.
Menopause – Guidance on management and prescribing HRT for GPs:
Based on NICE guidance 2015 and recent updates

4. POSSIBLE MEDICATIONS TO USE – there are alternatives available, see the BNF

HRT TABLETS* 2ND LINE* TRANSDERMAL*

SEQUENTIAL PREPARATIONS Estradiol 1mg + Norethisterone Estradiol + Dydrogesterone Estradiol 50mcg +
For patients with: sequential 1/10mg sequential Levonorgestrel 10mcg
• intact uterus SEQUI patch
• perimenopausal-under 1yr Estradiol 2mg + Estradiol + Dydrogesterone
or amenorrhoea Norethisterone sequential 2/10mg sequential Estradiol 50mcg +
(Non-androgenic) Norethisterone 170mcg
SEQUI patch
CONTINUOUS COMBINED Estradiol 2mg + Norethisterone TIBOLONE 2.5mg Estradiol 50mcg +
Bleed free HRT use if: 1mg CONTI Can be useful if: Levonorgestrel 7mcg
• Over 1yr since last period • Bloating on oestrogen CONTI patch
• >54y Estradiol 0.5mg + • Poor libido
• >3yrs on sequential HRT Dydrogesterone 2.5mg CONTI • Endometriosis Estradiol 50mcg +
Norethisterone 170mcg
Estradiol 1mg + Dydrogesterone CONTI patch
5mg CONTI
UNOPPOSED OESTROGEN Estradiol 1mg tablets ESTRADIOL PATCH
Post hysterectomy 25mcg, 37.5mcg, 50mcg,
Estradiol 2mg tablets 75mcg, 100mcg

Estradiol 0.06% gel

Estradiol 500mcg or
1mg gel sachets
TOPICAL VAGINAL Estradiol 10mcg
OESTROGEN vaginal pessaries

Estriol 0.1% CREAM

Estradiol vaginal ring
PROGESTOGEN ADJUNCT Medroxyprogesterone Levonorgestrel intrauterine
TO TOPICAL OESTROGEN 10mg d14-28 or 2.5-5mg daily˚ system 52mg
IF NO HYSTERECTOMY
Micronised progesterone Replace after five years
200 mg d14-28 or 100mg daily˚ as per FSRH guidance

*Use the lowest dose to control symptoms. ˚Day 14-28 (sequential – i.e. still giving periods), daily for continuous combined (bleed-free)

REFERENCES
1 https://www.nhlbi.nih.gov/science/womens-health-initiative-whi 2 J. C. Stevenson & R. D. T. Farmer (2020) HRT and breast cancer: a
million women ride again, Climacteric, 23:3, 226-228, DOI: 10.1080/13697137.2020.1735797 3 Original information courtesy of Mylan (n.d.).
The importance of the progestogenic component of hormone replacement therapy in women with a uterus. [online] Guidelines. Available
at: https://www.guidelines.co.uk/supplements/the-importance-of-the-progestogenic-component-of-hormone-replacement-therapy-in-
women-with-a-uterus/454874.article [Accessed 19 Sep. 2020].

For more resources visit: www.pcwhf.co.uk 10

This guidance was compiled by the PCWHF and was correct at the time of going to press. The PCWHF will undertake annual reviews of this guidance to ensure
it remains in line with best practice. The next review is due in November 2021. The guidance is for use by healthcare professionals only. The guidance has been
compiled by Dr Imogen Shaw for The Primary Care Women’s Health Forum and views expressed do not necessarily represent those of individuals or partners.
Declaration of interests are available at www.abpi.org.uk/our-ethics/disclosure-uk/. For further information, please contact [email protected]
DECLARATION: This resource was supported by an unrestricted educational grant from Viatris. Viatris has no editorial control over the content.