Menopause and HRT tips

• Age 45 or over - Diagnosis is clinical and hormone blood tests are not recommended
• Age < 45 - Consider:
  • FSH/LH
  • Estradiol
  • TFT, Prolactin

• treatment of menopausal symptoms
  • HRT can be used for as long as the patient feels that the benefits outweigh the risks
  • there are NO arbitrary limits
• treatment of early or premature menopause,
  • HRT should generally be offered and continued at least until the average age of the menopause, unless medical contraindication
• prevention or treatment of osteoporosis in women under the age of 60
  • HRT should be offered as first line for this indication if no contraindication (see osteoporosis guidance)

Not recommended for prevention of cardiovascular disease or dementia in absence of menopausal symptoms.

• Full assessment of symptoms and impact is required to lead to joint informed decision making
• If estrogen replacement is required, determine if vaginal estrogen, or systemic HRT

Indications for non-tablet route of Estrogen.

• Individual preference, based on correct information.
• Poor symptom control with tablet HRT.
• Side effects such as nausea with tablet.
• Bowel disorder which may affect absorption of tablet therapy.
• History of migraine (when steadier hormone levels which may be achieved with a patch may be beneficial).
• Lactose sensitivity (all tablet preparations of HRT contain lactose).
• History of gallstones.
• Current use of medications such as anti-epileptic medication which may interfere with the break-down of tablet HRT.
• Variable blood pressure.
• High triglyceride levels.
• Risk factors for deep vein thrombosis including Body Mass Index greater than 30, family history or past history of deep vein thrombosis or pulmonary embolus, after full discussion and specialist advice when necessary. Because risk of deep vein thrombosis increase with age, non-tablet route should also be considered when HRT is continued over the age of 60.

Oral still provides many benefits, convenient, uncomplicated, good bleeding control in continuous combined regimen.

Vaginal estrogen is very effective for urogenital symptoms, several types available, long term treatment recommended https://www.menopausematters.co.uk/local.php

Treatment of urogenital atrophy with vaginal estrogen requires long term treatment. Many women do not realise that the prescription should be continued, and often only receive enough for a few weeks. Some women require vaginal estrogen as well as systemic HRT and they can be used together.

Women having a spontaneous menopause at the usual age, should start on a low dose and only increase gradually (not more often than 3 monthly), if symptoms continue. At a later stage, the dose can gradually be reduced--we have seen several patients in their 60's and 70’s still on a high dose, this is rarely necessary and can cause problems such as bleeding and unnecessary investigations.

Women suffering from a premature or early menopause, often need to gradually increase to fairly high doses of estrogen to control symptoms, especially if a sudden, induced menopause.

In these women, it is reasonable to start at a medium dose and be prepared to increase at 3 monthly intervals.  

• Estrogen in a higher than medium dose should be associated with a proportionate increase in progestogen dose for endometrial protection
• Higher than licensed doses not recommended and other contributory factors (such as diet and lifestyle) should be addressed before increasing dose

• Sequential HRT is offered in the perimenopause, when there is still some ovarian function, as evidenced by periods still being present.
• Continuous combined (period-free) can be offered
  • at the age of 54, (when 80% of women do not have periods) or
  • when known to be postmenopausal as evidenced by having at least 1 year of no periods.

Advantages of continuous combined include patient satisfaction (most women prefer not to have periods) and better endometrial protection with daily progestogen.

If offering continuous combined, advise that some bleeding within the first 6 months is common and only needs to be investigated if bleeding persists beyond 6 months, or occurs at a later time.

HRT aims to replace estrogen. Unless the patient has had a total hysterectomy, some form of progestogen should be used in addition.Please note:

• Many HRT preparations have similar names, eg Evorel is an estrogen only patch whereas Evorel Conti contains estrogen and progestogen. Check the brand and components carefully
• Mirena can be used for the progestogenic endometrial protection along with systemic estrogen, but only if it is "up-to-date" which means is within 5 years of insertion. (Mirena is licensed for 4 years for endometrial protection, but nationally it is accepted that 5 years is OK). If inserted after the age of 45 for contraception, it can be continued after 5 years, but if adding in systemic estrogen, it MUST be up-to-date

If Mirena removed and patient has been taking systemic estrogen, HRT MUST be changed to one containing both estrogen andprogestogen and should be clearly documented.

Inadvertent unopposed estrogen

A number of patients are referred having being identified as having had a period of unopposed estrogen. In the absence of abnormal bleeding:

• < 3 months of unopposed estrogen - change regimen to include appropriate progestogen
• 3 to 6 months – refer if other risk factors, e.g. high BMI, H/O PCOS. If none, change regimen
• > 6 months - refer
• Abnormal bleeding - refer

• Perform vaginal and speculum examination and then refer as Urgent
• Sequential therapy - change in pattern of bleeding including increased duration, frequency and/or heaviness, and irregular bleeding.
• Continuous combined therapy or tibolone - if still bleeding after 6 months of therapy or if bleeding occurs later after a spell of no bleeding.
• Only use Urgent, suspicion of cancer, option if concerns on examination, eg suspicion of cervical cancer
• Incidence of endometrial cancer in patients with bleeding problems on HRT is extremely low, unless unopposed estrogen taken, or regimens with high dose estrogen and inadequate progestogen
• No need to advise stopping HRT prior to appointment, but OK to do so if patient wishes to stop

Most common reason for referral is unscheduled bleeding on continuous combined HRT. Bleeding problems can be reduced by

• When starting HRT, start with low dose and aim for lowest effective dose
• Consider oral continuous combined HRT if no VTE or cardiovascular risk factors, since chance of amenorrhoea is higher than with transdermal continuous combined HRT Postmenopause : Menopause Matters
• If transdermal continuous combined HRT indicated, offer off license half continuous combined patch, rather than medium dose (Evorel conti or Femseven conti) to offer low dose when possible Postmenopause : Menopause Matters
• If higher dose estrogen required (after giving any type of HRT at least 3 months to show effect, addressing other factors contributing to symptoms, eg diet and lifestyle, patch adherence..) increase progestogen proportionately
• Try to avoid the need for regimens taking estrogen and progestogen separately, since progestogen can be missed leading to higher chance of endometrial stimulation and hence bleeding. The need for separate progestogen is inevitable if using estrogen gel or spray, since these are estrogen only, but these should be a later option, not offered first line
• Uterine bleeding with hormone therapies in menopausal women: a systematic review. J H Pickar1 2, D F Archer 3, S R Goldstein et al. Climacteric 2020 Dec; 23(6):550-558

• Allow 3 to 6 months on therapy to ensure full effect
• Inadequate estrogen dosage - increase dose or change route
• Poor absorption due to bowel disorder - change to transdermal
• Drug interactions eg. barbiturates, phenytoin, carbamazepine - increase oral dose or change to transdermal
• Poor patch adhesion - change delivery system. Patch position—buttocks best absorption. Some women absorb best from patch, others from gel, others from spray and some respond best to oral
• Incorrect diagnosis - other conditions such as thyroid dysfunction, hypertension and poor glucose control and lifestyle factors can cause similar symptoms to menopause
• Unrealistic expectations - HRT can help symptoms due to estrogen deficiency but is not an answer to all problems!

• Only recommended indication is persistent troublesome low libido after all other contributory factors addressed, including adequate estrogenisation, relationship issues, life stresses!
• If decision made to start, advise that effect is moderate at best and view it as a trial. Stop if no benefit after 6 months
• Before starting, check total testosterone—if already at higher end of normal female physiological range, don’t start—unlikely to provide any benefit since aim is to keep within normal range
• Check total testosterone at 3 months and, if continuing, 6 to 12 monthly. Warn re side effects and reduce dose if above normal range

When commenced on HRT or if HRT is changed, review should be arranged after 3 months.

Once settled on HRT or vaginal estrogen, review should be at least annual, to assess effectiveness, presence of side effects, update on new information, help with ongoing risk/benefit analysis.

When to refer depends on your experience and confidence but in general terms, the following apply:

1. SIDE EFFECTS Persistent side effects. See Menopause Matters Side effect management for initial management advice
2. POOR SYMPTOM CONTROL Inadequate control despite following Menopause Matters Poor symptom control advice
3. BLEEDING PROBLEMS
   • Sequential therapy - change in pattern of bleeding including increased duration, frequency and/or heaviness, and irregular bleeding.
   • Continuous combined therapy or tibolone - if still bleeding after 6 months of therapy or if bleeding occurs later after a spell of no bleeding.
4. COMPLEX MEDICAL HISTORY
5. PAST HISTORY OF HORMONE DEPENDENT CANCER
6. INDIVIDUAL REQUEST

The interactive decision tree on www.menopausematters.co.uk/tree.php aims to help with prescribing decisions.

Telephone helpline, Thursdays 9am to 12, 01387 241121 – run by SR Katrina Martin who is happy to help with any queries and can also be contacted by email at katrina.martin@nhs.scot