Menopause/HRT

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Questionnaire/history:

Menstrual history?

Vasomotor symptoms:

- Hot flushes?

- Excessive sweating?

- Night sweats?

- Headaches?

- Palpitations?

Cognitive impairment and mood disorders?

- Poor concentration?

- Poor memory?

- Difficulties in multi-tasking?

- Sleep disturbance?

- Fatigue?

- Anxiety?

- Low mood?

- Mood swings?

- Irritability?

Urogenital symptoms?

- Vulvovaginal irritation, discomfort, burning, itching and/or dryness?

- Dyspareunia?

- Reduced libido?

- Dysuria, urinary frequency and urgency?

- Recurrent lower urinary tract infections?

Other?

- Joint and muscle pains?

If amenorrhoea: other causes (eg pregnancy, depo, POP, implant, ablation)?

Lifestyle factors?

- Smoking?

- Alcohol?

- Exercise?

- Nutrition?

Need for ongoing or future contraception?

Cervical screening history?

Bone health and risk of osteoporosis?

Treatment goals?

Previous treatments?

Past medical history?

Family history?

- Premature menopause or POI?

- Venous thromboembolism?

- Hormone-dependent cancer?

Current medication?

Drug allergies?

Examination:

BP?

BMI?

Pelvic examination (if hx, sxs or FH of gyn. disease)?

Investigations: Estrogen blood tests not evidence based, no specific recommendations, it does not correlate well with the clinical picture (risk of overtreating, absorption problem?, one smear, then wash the hands, skin at forearms thinner, so better absorption, swab to oral estrogen for 2-3/12 to see if absorption problem, consider support from menopause clinic) FSH, LH, oestrogen (rarely AMH) (ideally on D3-5 of a period) if not on combined hormonal contraception or HRT and:

Suspicion of premature menopause/POI?

Atypical symptoms?

Reduced fertility?

> 50 years using progestogen-only contraception?(If FSH level in the premenopausal range to continue contraception and FSH level control 1 year)

(Note: no absolute values to determine menopausal status, single FSH > 30 IU/L indicates a degree of ovarian insufficiency, but not necessarily sterility, to check for an elevated FSH level on 2 samples taken 4-6 weeks apart)

If perimenopausal problems with menorrhagia and/or dysfunctional uterine bleeding (DUB) to consider ultrasound, hysteroscopy/biopsy

Diagnosis:

Perimenopause (irregular cycles of ovulation and menstruation (until 12 months after the last menstrual period))

Menopause (no period for at least 12 months (and is no hormonal contraception))

Early menopause (cessation of ovarian function btw 40 and 45 years, in the absence of other causes of secondary amenorrhoea)

Premature menopause (loss of ovarian function before the age of 40 for example following bilateral oophorectomy)

Premature ovarian insufficiency (POI, also known as premature ovarian failure) (transient or permanent loss of ovarian function before the age of 40 years characterized by menstrual disturbance (amenorrhoea or oligomenorrhoea) and potential spontaneous resumption of ovulation, menstruation, and spontaneous pregnancy + elevated FSH (> 30 IU/L on 2 blood samples taken 4-6 weeks apart) (LH, oestradiol, prolactin, testosterone, TSH may be helpful, not routinely AMH)

Genitourinary syndrome of menopause

Management:

General advice given:

Weight loss (if applicable)

Well-balanced diet: ideally ‘5 a day’, and high in phytoestrogens (eg lentils, peanuts), avoiding spicy foodVitamins [B, C, D, E] & minerals [Ca, Mg, Zn, Cu, Se, Mn] if required

Regular exercise (CV, strength training and pelvic floor exercise (eg squeezy app))

Adequate sleep

Stress reduction, to consider CBT for stressSmoking, alcohol and caffeine cessation

For hot flushes and night sweats: wearing loose thin layers of clothing, turning down central heating, sleeping in a cooler room, leaving a door or window open, using a fan or aircon, menopause quit

For sleep disturbances: avoiding exercise late in the day and maintaining a regular bedtime

For mood and anxiety disturbances: adequate sleep, regular physical activity and relaxation exercises

For cognitive symptoms: exercise and good sleep hygiene

To seek occupational health advice if support is needed in the workplace

Manage CV RF

Engagement with national screening programmes

HRT does not provide contraception

Potential fertility for 2 years after last menstrual period if < 50 years and for 1 year if > 50 years

In general contraception can be stopped with 55 years

Progestogen-only methods of contraception safe to use alongside cyclical HRT

Combined hormonal contraception in eligible women < 50 years can be used as an alternative to HRT for relief of menopausal symptoms and prevention of loss of bone mineral density, to switch to a progestogen-only method of contraception at 50 years of age, if needed

Perimenopausal problems:

Expectant management

Tranexamic acid, mefenamic acid

Progestogens

Mirena IUS

Endometrial ablation/resection

Hysterectomy

Menopause:

Advised:

Stages of menopause

Common symptoms

Short- and long-term health implications

MSK changes in menopause: reduced oestrogen causes decreased muscle mass and strength and collagen in connective tissue with ligaments & tendons becoming stiffer and increased injury risk, also decreased bone density up to 10% mass in first 5 years with lifetime risk of fracture 50% after age of 50, and raised cortisol causes increased sensitivity to pain and muscular aches

Support organizations (eg Daisy Network, Menopause Matters, NHS Health A to Z, Rock My Menopause, RCOG, WHC/BMS)

HRT

Aim of HRT: symptom control or reduction by at least 50% No age limitation if risk factors are continuously and regularly monitored

Benefits:

Feeling better

Improved QOLControls the typical symptoms

Reduces risk of fragility fractures Improvement of muscle mass and strength (limited evidence)

Endometrial cancer: risk decrease with continuous combined HRT

Risks (if transdermal option and newer generation estrogens): Overall: ALL risks are low in statistical & medical terms compared to modifiable risk factors All cause mortality: life expectancy unlikely to change with the use of combined HRT For people aged 45+ HRT as a treatment option for menopause-associated sxs, overall, taking HRT is unlikely to affect life expectancy

VTE: baseline AR: 12.5/1000 over 5 yrs, not greater with transdermal preparations (ARI (oral HRT): 5/1000))

CHD: no risk increase with combined HRT

Stroke: no risk increase with transdermal oestrogen (small increase with oral oestrogen)

CVD: no increase if started younger than 60 years, combined HRT does not affect the risk of dying from CVD

T2DM: no increase

Dementia: minimal

Breast cancer: Similar to the risk of OCP

Oestrogen only HRT: little or no risk increase with no legacy risk

52mg LNG-IUS: low to no risk increase

Combined HRT: lowest risk if used < 5 yrs, increased risk if used > 1 y, dependent on duration of treatment (irrespective of type of oestrogen or progestogen or route with slightly lower risk with cyclical compared with continuous combined HRT)

Oral levonorgestrel: longest legacy risk

With 5 years HRT use in 40s and 50s +5/1000 cases if oestrogen-only HRT, +14/1000 cases if sequential combined HRT and +20/1000 case if continuous combined HRT, with 10y HRT use extra cases double as above

Risk reduces after stopping HRT

Very small increase in risk of death from breast cancer with combined HRT

Vaginal oestrogen: no increased risk of breast cancer

Ovarian cancer: small risk increase with combined HRT (in women who use HRT for 5 years from around age 50 years 1 extra ovarian cancer per 1000 users and about 1 extra ovarian cancer death per 1700 users)

Endometrial cancer: risk may slightly increase with sequential combined HRT

Decision aids: NICE: HRT and the likelihood of some medical conditions MHRA: Summary of HRT risks and benefits during current use and current use plus post-treatment from age of menopause up to age 69 years, per 1000 women with 5 years or 10 years use of HRT

MHRA: Detailed summary of relative and absolute risks and benefits during current use from age of menopause and up to age 69, per 1000 women with 5 years or 10 years use of HRT

Menstruating:

Cyclical/sequential HRT

Oestrogen every day and progestogen for 10 to 13 days per months (induction of monthly withdrawal bleed in about 85%)

Amenorrhoeic:

Start continuous HRT

If 52mg LNG-IUS add oestrogen only at any time (check IUS is not more than 5 yrs old)

No uterus:

Continuous oestrogen

Entrometriosis:

Combined HRT

Sub-total hysterectomy:

Prosterone challenge

Vaginal symptoms:

Vaginal moisturisers

Vaginal oestrogens

Always examine before prescribing

Perimenopause:

Oestrogen every day and progestogen for 10 to 13 days per months (induction of monthly withdrawal bleed in about 85%)

Lenzetto 1.53mg/dose transdermal application, apply 1 spray on the forearm once daily, increased to 2 sprays once daily after at least 4 weeks of continuous treatment prn, max dose 3 sprays daily, 56 doses

Oestrogel Pump-Pack 0.06% gel, apply 1.5 mg (2 pumps) once daily continuously, increased, if necessary, up to 3 mg after 1 month continuously, to be applied over a large area, 80g

Estradiol (Evorel) transdermal patch 50mcg/24 h, apply 1 patch twice weekly continuously, started within 5 days of onset of menstruation (or at any time if cycles have ceased or are infrequent), therapy should be initiated with Evorel 50 patch; subsequently adjust according to response; dose may be reduced to Evorel 25 patch after first month if necessary for menopausal symptoms only, 8

Utrogestan capsule 100 mg, 200 mg at bedtime (not with food) on days 15-26 of each 28-day oestrogen HRT cycle, alternatively 100 mg once daily on days 1-25 of each 28-day oestrogen HRT cycle, 3 x 30

Postmenopause or 53+:

Progestogen can be taken every day along with the oestrogen (may cause some bleeding in the first 6 months, but should not induce bleeding thereafter)

Usually one (two) year(s) after no periods

After 5 years of use over age 45 years or by age 54 years (whichever is first)

If already on something that makes amenorrhoeic (e.g. POP/Mirena)

Patient wishes to tryIf patients gets irregular bleeding, swop to sequential/cyclical HRT for a few months then back again

Utrogestan capsule 100 mg, 100 mg at bedtime (not with food), (3 x 30)

Consider higher dose if on higher oestrogen dose:Micronised progesterone 300 mg for 12 days a monthsMicronised progesterone 200 mg on a continuous regimen

Consider an USS to see if endometrium thickens

Mirena Coil:

In both the perimenoause and the postmenopause, particularly helpful when there are heavy bleeds with sequential HRT, when contraception is still required along with HRT, and when there are side effects from the progestogen part of HRT

Oestrogen can be taken in the form of a tablet, patch, gel, vaginal ring or implant and tried for 3 months (if malabsorption, lactose sensitivity or migraines better none oral form)

Limited data for continued usage beyond age of 60 years, and not usually appropriate to start > 60

Indication for non-tablet route:

Individual preference

Poor symptoms control/side effects/malabsorption

History of migraine (when steadier hormone levels are required)

Lactose sensitivity (all HRT tablets contain lactose)

History of gallstone

Current use of medication such as anti-epileptic medication which may interfere with the break-down of tablet HRT

Vasomotor symptoms:

With a uterus: transdermal or oral combined preparation (with a progestogen which prevents oestrogenic stimulation and thickening of the womb lining)

Without a uterus: transdermal or oral oestrogen-only preparation

Eligible women < 50: HRT or combined hormonal contraception

Mood disorder:

Transdermal or oral HRT

Urogenital symptoms:

Low-dose vaginal oestrogen (Note: some women on systemic HRT may also benefit from additional low-dose vaginal oestrogen))

If no relief: specialist advice about increasing the dose

If low-dose vaginal oestrogen not tolerated or contra-indicated: oral ospemifene

Vaginal moisturizer and lubricants alone or in addition to vaginal oestrogen

Low dose vaginal oestogens:

Estriol Estriol cream 0.01%

Ovestin cream 0.1%

Blissel vaginal gel 0.01% - specifically marketed for women with a hx of breast cancer

Imvaggis pessaries 0.03mg

Estradiol

Vagirux 10mcg vaginal tablets, one tablet daily for 2 weeks, then one tablet twice a week, (24 pessaries)

(reusable applicator, greener option)

Vagifem pessaries 10mcg

Gina pessaries 10mcg (OTC – 30 pounds/months)

Estring vaginal ring 7.5mcg/23 hours – ‘strongest’ form of vaginal estradiol, inserted into upper third of vagina, lasts for 3 months

Gynest cream (Estradiol 0.1%), maybe used on vulva

Prasterone (DHEA)

Prasterone (DHEA) vaginal pessary 6.5mg daily

Can combine cream and pessaries

Can combine with vaginal moisturisers – use at a different time

Ovestin cream (without applicator) for more immediate relief and Blissel vaginal gel with the option to drop Ovestin cream

Advantages:

Avoids enterohepatic circulation

Lowest possible dose

No endometrial stimulation

Cyclical progestogens unnecessary

No systemic side effects

Exerts mainly local effect

Acceptable following breast cancer

Disadvantages:

No systemic benefits (for bones, vasomotor and psychological symptoms)

Mode of administration

Altered sexual function:

Indication:

Low libido (specifically termed Hypoactive Sexual Desire Disorder) with menopause if HRT alone is not effective Baseline total testosterone prior to initiation (more accurate representation of the therapeutic response than free testosterone or free androgen index) If if >=1.4nmol/L or >=75% of local lab ref range then TRT is nor recommended To aim for upper end of normal Repeat in a few weeks time, if total testosterone >=2.0nmol/L (110%) reduce dose & repeat in 2-4 weeks Once dosage is right, recheck at 3 months, 12 months, then annually if stable

If clinical improvement & in the physiological range continue, if no improvement at 6 months, stop Take in the morning before application of TRT, ensure no contamination of skin (avoid arms where HRT is applied, ideally apply TRT below the waist

Testim gel 1% in 5 ml tube, starting dose 0.5 ml (5mg) (1/2 finger nail) per day, if that is not enough a full finger nail, one sachet should last for 10 days Testogel 2.5g sachets containing 0.5mg testosterone, starting dose 1/8 of sachet (approx. 5 mg) per day, one sachet should last 8 days

Tostran gel 2% canister containing 60g testosterone, starting does 1 pump of 10mg alternate days, one canister should last for 240 days

AndroFeme cream 1% cream in 50 ml tube, starting dose 0.5 ml per day, one tube should last for 100 days (licensed for women)

Safe, SE uncommon within the physiological range, supraphysiological levels have no benefit but possible SEs like acne, increased body hair at the application site, hirsutism, alopecia, mood changes; deeper void, clitoromegaly, theoretical risks, but rare with physiological doses, masculinization regimes use 10x the dose

Testosterone implants

Bioidentical hormone replacement therapy not recommended by the BMS and NICE, not evidence of effectiveness

Review

After 3 months if HRT has been started or changed, then 6-12 monthly

BP and weight

Reinforced information and lifestyle advice

Assessed efficacy and tolerability of treatments

If bothersome adverse effects or persistent symptoms: options:

Reduce dose of oestrogen

Change the dose or type of progestogen

Alter the route of administration

Switch to combined oestrogen/bazedoxifene acetate preparation if progestogen-containing therapy not appropriate

Sudden change in menstrual pattern -> 2-week referral if a gynaecological cancer suspected

If persistent symptoms, consider alternative cause

Review the duration of HRT treatment (if HRT was started in the perimenopause, discuss the option of changing the treatment regimen and/or reducing the dose of oestrogen)

Check BP and weight

Decision on when and how to stop

For vasomotor symptoms most women require 2-5 years of treatment, but some may need longer

Women with premature menopause of POI should take HRT up to the average age of natural menopause (51 years in the UK) after which the need for ongoing HRT should be reassessed

HRT may be gradually reduced over 3-6 months, or stopped suddenly, depending on the woman’s preferences

If troublesome symptoms recur, options include restarting HRT at a low dose, or considering alternative non-hormonal treatments

Vaginal oestrogen preparations may be required long term, but regular attempts to stop treatment, such as annually, can be made

Non-hormonal HRT

Vasomotor symptoms:

SNRI (eg venlafaxine MR 37.5mg for 1 week, then increased to 75mg if needed): more effective than SSRI, and if woman on tamoxifen and SSRI should be avoided

SSRIs (eg sertraline, paroxetine 10mg, fluoxetine 20mg, citalopram 20mg): interaction with tamoxifen (reduces efficacy)

Gabapentin 300mg od for 1-2-52, then bd for 1-2 weeks, then tds: reduces hot flushes, aids aches, pains and paraesthesia, CD – addictive potentialPregabalin: better tolerated

Clonidin (25-)50 mcg bd for 2 weeks, then increased to 75mcg bd: SEs significantFezolinetant (Veoza) (neurokinin 3 receptor antagonist) 45mg: for moderate to severe vasomotor symptoms, maybe used in women with post breast cancer, needs baseline LFT and every 3/12

CBT

Mood disorder:

Self-help resources

CBT, menopause-specific CBT

Antidepressant treatment for a confirmed diagnosis of depression and/or anxiety

Urogenital symptoms:

Vaginal moisturizer (YES, Replens MD or Hyalofemme at least twice weekly)

Vaginal lubricants if insufficient vaginal secretions for comfortable sexual activity

Alone or in addition to vaginal oestrogen preparations

Ospemifene tab 60 mg

Vaginal laser therapy

Complementary therapies: