Primary care HRT guidance

Disclaimer: For up-to-date references supporting the following advice, please refer the clinical resources at the bottom of this page

On this page


HRT or MHT Hormone replacement therapy or menopausal hormone therapy
Menopause Age 45–55 with outliers above 55
Early menopause Age 40–45
Perimenopause Change in cyclical menstrual pattern with or without psychological or physical symptoms (including depression, anxiety, low libido). Often causing distress and affecting quality of life.
Postmenopausal 12 months of amenorrhea, average age 51
Premature ovarian insufficiency (POI) Elevated FSH with oligomenorrhea or amenorrhea diagnosed under age of 40
Premenstrual syndromes

Usually psychological symptoms but may be physical. Causing distress and having an adverse effect on quality of life

Also includes: Premenstrual dysphoric disorder (PMDD) and premenstrual exacerbation

HRT formulations

  • Synthetic hormones: 100% synthesised, manmade eg tibolone, progestogens.
  • Natural body-identical hormones: Licenced hormones e.g. all estradiol preparation and Utrogestan. Base molecule derived from either soy or yams and modified to be identical to ovarian estradiol, progesterone or testosterone
  • Compounded bioidentical hormones: Unregulated unlicensed natural bioidentical hormones with no extant safety data eg transdermal progesterone cream and oral lozenges
  • Equine estrogens: Obtained from pregnant mares (horses) urine. No usually prescribe but available as premarin or premique. Most VTE risk data comes from studies using this, suggesting a class risk effect

Hormone replacement therapy

  • HRT choice is based on a number of factors: Patient choice, patient adherence, safety and efficacy 
  • Anecdotal evidence supports the use of over the counter (OTC) supplements and alternative therapies although, there is minimal validated evidence of efficacy.
  • HRT is licenced for women who present with symptoms consistent with the menopause that are having a significant impact on their quality of life. 
  • HRT provides immediate symptom relief of menopause symptoms both psychological and physical, as well as long-term protection against osteoporosis, cognitive decline including Alzheimer’s disease and cardiovascular risk reduction. Risk data is available via the British Menopause Society (BMS).
  • In POI or early menopause there is a risk of osteoporosis developing before the average age of the menopause. A baseline BMD is advised with effective estrogen replacement continued until at least the age of 51. The reversal of low bone density is achievable over time with adequate estrogen replacement, with the goal of restoring healthy bone density.
  • Until menopause status is confirmed, pregnancy risk remains and contraception should be advised. For some women this may be up until at least the age of 55. 
  • There is no definitive age cut off for HRT use as this should be determined by individual with risks versus benefits. Persistent symptoms on cessation of HRT or the need for bone protection are indicators for on-going treatment.

Good clinical practice points

  • HRT choice is based upon a number of factors: Patient choice, patient adherence, safety and efficacy 
  • Most women can effectively be managed in primary care, with the use of NICE and British Menopause Society guidelines to inform clinical decision making
  • Only women under the age of 45 require FSH/LH to aid diagnosis
  • Women diagnosed with POI should have HRT until at least the age of 51
  • Transdermal estrogen has a non-significant risk for MI, CVA, Stoke, VTE in any age group
  • Oral estradiol is associated with a significant but low VTE risk and may be suitable in women with a low risk
  • For women with and intact uterus, natural bioidentical progesterone may be preferred due to its non-significant breast cancer risk. Dydrogesterone also demonstrates a non-significant breast cancer risk. May be used as an alternative to utrogestan
  • Discuss future pregnancy options and contraceptive needs in POI and perimenopause

 Considering risks and benefits

  • Licensed benefit: symptom relief which is not a defined list an may include fatigue, depression, anxiety, low libido etc and is not age dependant, osteoporosis prevention
  • Additional health benefits: reduced CVD  and Alzheimer’s disease
  • Risks of HRT are determined by patent age at starting HRT and their past medical history
  • Natural menses continue until the age of 51 promote CVD, bone and brain health. HRT used up until this age is considered equally safe and beneficial and should not be stopped prematurely.
  • Refer to secondary care before initiating HRT, where risks appear to outweigh benefit or commencing over the age of 60
  • The licensed use of HRT use is not limited by its duration of use but yearly risk and benefit assessments should be undertaken
Past medical historyHRT choices—decision-makingComment
MI, CVA, Stoke, VTE

Transdermal estradiol does not significantly increase event risk

Increasing transdermal estrogen doses is not associated with increased event risk

Transdermal estradiol always recommend if women with a pre-existing risk history

Oral estradiol increases risk event and not recommended unless there are no other pre-existing risk factors

Norethisterone (NET) may be associated with significant increased VTE risk

Oral estradiol is contraindicated in MI, CVA, stoke, VTE history

Suspected coagulopathies should be assessed by a haematology specialist with an interest in HRT

NET not recommended as a first line progestogen

Migraine +/-aura

Transdermal estradiol does not significantly increase VTE risk

Transdermal estradiol is recommend in women with a pre-existing risk history 

Oral estradiol is contraindicated in history of migraine with aura 

Breast Cancer or other hormonal cancer

Natural body-identical progesterone has a non-significant breast cancer risk with HRT

Medroxyprogesterone (MPA) may be associated with significant increased breast cancer risk

Natural body-identical progesterone is the hormone of choice

MPA not recommended as a first line progestogen

Clinical considerations and trouble shooting

  • Common problems with HRT are: uncontrolled symptoms, suboptimal estrogen replacement or irregular bleeding
  • Where problems cannot be resolved after trying alternative options, refer to a menopause specialist or appropriate clinical pathway 
Bone density

The younger the women at diagnosis the greater the risk of developing osteoporosis and increased morbidity

Confirmed low bone density should be actively treatment with a therapeutic estrogen replacement dose

Encourage Vitamin D, magnesium, Vitamin K supplements and weight bearing exercises 

Regular bone scans per guidance or as directed by the specialist

A serum estradiol of at least 250pmol/l is required to promote bone metabolism and reversal of bone loss – change estradiol dose and brand as required

A serum estradiol of at least 250pmol/l is required to promote bone metabolism and reversal of bone loss – change estradiol dose and brand as required

Refer to rheumatology if HRT is optimised but bone health not improving

Refer to menopause clinic if HRT is not optimised and bone health not improving

Hormonal depression and anxiety in perimenopausal or postmenopausal women

PMS/PMDD and the menopause present with a high incidence of suicide

Antidepressants are not recommended as first line treatment in the NICE guideline

Effective HRT will alleviate hormonal depression by replacing stable physiological hormone levels and serotonin equilibrium

 Co-morbid endogenous depression should be treated concurrently

Safety netting: Women with a history of suicidal risk or mental health disorders should have an up to date risk assessment and referral to mental health services 

Hormonal depression is best relieved with good stable estrogen replacement

The effective dose replacement is individual and the maximum licensed dose and alternative brands should be tried

High estrogen levels are often required, between 400-600pmol/l. Referral to secondary care may be indicated if off licence doses of estrogen is required

Progesterone or progestogen intolerance

The development of progestogenic side effects often describe as PMS

A common limiting factor with the HRT, COCP, POP and IUS

There is usually at least 1 progestogen replacement that will be tolerated

Utrogestan is least likely to case side-effects and may be used off-label per vaginum to limit this effect

Contraception needs must be advised

Due to their synthetic nature, the COCP or POP are not usually effective, often worsening depressive symptoms

Due to their synthetic nature, the COCP or POP are not usually effective, often worsening depressive symptoms

Androgenic progestogens eg NET are more likely to provoke side effects and reduce adherence

Natural body-identical progesterone is least likely to precipitate side effects and can be used per vagina (off label)

The Mirena (licenced use) or  Kyleena (off label) are excellent options due to low systemic effects

The evidence does not support the use of transdermal compounded progesterone for the protection against endometrial hyperplasia or atypia in licensed HRT

Premenstrual syndromes


Hormonal depression and anxiety – in perimenopausal or postmenopausal women

Progesterone intolerance

Refer to the National Association of Premenstrual Syndrome guidelines (NAPS).

 A national support network for women with PMS/PMDD with evidence base treatment guidelines and patient support

Resistant PMS may require cycle suppression with GnRHa or ultimately surgery

Safety netting: Women with a history of suicidal risk or mental health disorders should have an up to date risk assessment and referral to mental health services 

Irregular bleeding on a sequential combined HRT (intact uterus)

A sequential combined HRT is only suitable for women who are perimenopausal or still having regular menstrual cycles

The licenced dose and duration of use should be adhered to when taking progestogen or progesterone

A lower dose or shorter duration significantly  increases the risk of irregular bleeding and potential for endometrial hyperplasia or atypia

Missing doses may be attributed to irregular bleeding but should still be investigated due to the risk undiagnosed pathology

All irregular bleeding should be investigated if continues beyond 4-6 months

A timed ultrasound scan after an induced bleed is advised

The endometrial result should about 5mm or less although there is no standard in menstruating women

Any abnormal pathology eg endometrial polyp, should be followed up according to your local care pathway

Changing to a more androgenic progestogen eg NET, or the Mirena is recommended

Any  persistent abnormal irregular bleeding, should be followed up according to your local care pathway

Where a specialist has recommended an un-licenced progesterone regimen twice yearly endometrial surveillance is indicted post withdrawal bleed

Unresolved menopause symptoms—symptomatic on HRT 

Unresolved symptoms often correlates with poor adherence or lack of effective absorption

This is one of the few occasions performing FSH/LH and serum estradiol have clinical value as other gynaecological disorders may present similarly

Symptoms generally resolved when serum estradiol >250pml/l. There is no upper limit but generally not >600pmol

If symptomatic on HRT use the full licensed dosing range, change brand or change route of administrations; with oral estradiol the last option (unless contraindicated)

Vaginal atrophic symptoms

Systemic HRT does not always resolve vaginal atrophic symptoms, but suboptimal replacement should be addressed

Local estrogen can be used to relieve symptoms whether or not systemic HRT is being used

HRT risks are not increased by using both systemic and local estrogen together

Any regular over the counter vaginal lubricants (for intimacy) and moisturiser (for daily rehydration) is advised in addition to or instead of local estrogen

A year of Vagifem 10mcg use is equivalent to one oral table of estrogen

Previous evidence based used of 25mcg Vagifem twice weekly is still extant. Therefore, Vagifem 10mcg can be used 4-5 times per week if symptoms persist

Where other vulval pathology is suspected a referral to dermatology vulval clinic is advised

Persistent recurrent UTI or vaginal infection to be referred to the respective specialist clinics

Under age 45—uncertain diagnosis 

NICE guideline advise this is the only indication for using FSH/LH to aid diagnosis to aid exclusion of other gynaecological disorders that may present similarly

Discuss family planning, egg freezing, ovum donation, surrogacy, adoption

Offer contraception due to risk of sporadic ovulation or  unplanned pregnancy

Refer women under the age of 40 with POI to a specialist POI clinic, with baseline investigations, USS and BMD where possible

Early menopause may be treated as for all menopause women, but with greater consideration for effective estrogen replacement for long-term bone, heart and brain health and continued until at least the age of 51 or longer

POI Daisy network

Differential diagnosis

A full health history should exclude any red flags prior to starting HRT

Unresolved symptoms may also indicate other comorbid diseases

Persistent unresolved symptoms may indicate other health disorders and should be excluded 

NICE CKS: What else might be causing symptoms

Prescribing practice points

  • The estrogen dose should alleviate symptoms and be sufficient for bone health
  • Use the full dosing range to achieved clinically therapeutic outcome
  • HRT is a long-term treatment and be prescribed accordingly eg 6/12 supply per time once stabilised
  • Unless there are supply shortages, continue branded prescriptions that are acceptable to the patient and effective
  • In times of supply shortages use any alternative brand at the equivalent dose should be prescribed
  • Only recommend licenced products
  • All oral and transdermal estrogens are equally effective. Individual pharmacodynamics and pharmacokinetics can result in variable response requiring tailored prescribing or brands and doses
  • Refer to the BMS web site for comparative prescribing options

Back to the top
Back to main page

Clinical resources 


angusws Claire Bellone George Vasilopoulos