6.4.1 Female sex hormones and their modulators

Further guidance supporting the prescribing of HRT preparations and the clinical management of menopause can be found here Guidance on the management of menopause

Oestrogen only

For women without a uterus, oestrogen-only HRT is appropriate, however, in endometriosis, endometrial foci may remain despite hysterectomy and the addition of a progestogen should be considered in these circumstances. For women with a uterus, oestrogen plus progestogen HRT is recommended. A progestogen should be added to reduce the risk of cystic hyperplasia of the endometrium and possible transformation to cancer.

Vaginal oestrogen preparations to be used in the relief of vaginal atrophy can be found here 7.2.1 Preparations for vaginal and vulval changes

Conjugated oestrogen, equine

Premarin®

(Conjugated equine oestrogens)

  • Tablets 300 micrograms, 625 micrograms, 1.25mg (£2.02, £1.34, £1.19)

Indications

  • Menopausal symptoms
  • Osteoporosis prophylaxis

Dose

  • Menopausal symptoms, 0.3–1.25mg daily continuously
  • Osteoporosis prophylaxis, 0.625-1.25mg daily continuously; with cyclical progestogen for 12-14 days of each cycle in women with a uterus

Notes

  1. Prescribe by brand (to aid identification where products contain multiple ingredients, or to prevent confusion where multiple brands contain similar ingredients)

Estradiol

Elleste solo®

(Estradiol)

  • Tablets 1mg, 2mg (£1.69)

Indications

  • Menopausal symptoms
  • Osteoporosis prophylaxis

Dose

  • Menopausal symptoms: 1 mg daily
  • Menopausal symptoms not controlled with lower strength or osteoporosis prophylaxis: 2 mg daily
  • Start treatment on day 1 of menstruation (or at any time if cycles have ceased or are infrequent), to be taken with cyclical progestogen for 12–14 days of each cycle in women with a uterus.

Notes

  1. Prescribe by brand (to aid identification where products contain multiple ingredients, or to prevent confusion where multiple brands contain similar ingredients)
Evorel®

(Estradiol)

  • Patches 25 micrograms, 50 micrograms, 75 micrograms, 100 micrograms per 24 hours (£4.12 = 75 micrograms)

Indications

  • Menopausal symptoms
  • Osteoporosis prophylaxis

Dose

  • 1 patch to be applied twice weekly continuously.
  • Start within 5 days of onset of menstruation (or at any time if cycles have ceased or are infrequent), to be used with cyclical progestogen for 12–14 days of each cycle in women with a uterus.

Notes

  1. Prescribe by brand (to aid identification where products contain multiple ingredients, or to prevent confusion where multiple brands contain similar ingredients)
  2. 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

Oestrogen with progestogen

Continuous Combined Preparations

Continuous combined preparations are not suitable for use in the perimenopause or within 12 months of the last menstrual period; women who use such preparations may bleed irregularly in the early stages of treatment—if bleeding continues endometrial abnormality should be ruled out and consideration given to changing to cyclical HRT.

Conjugated oestrogens with medroxyprogesterone

Premique®

(Conjugated oestrogens with medroxyprogesterone)

  • Low dose modified release tablets (300 micrograms + 1.5mg) (£2.17)

Indications

  • Menopausal symptoms

Dose

  • 1 tablet daily, continuously

Notes

  1. Prescribe by brand (to aid identification where products contain multiple ingredients, or to prevent confusion where multiple brands contain similar ingredients)
  2. Premique contains medroxyprogesterone and is less androgenic.
  3. Animal source of oestrogen.

Estradiol with norethisterone

Kliofem®

(Estradiol with norethisterone)

  • Tablets (2mg + 1mg) (£3.81)

Indications

  • Menopausal symptoms
  • Osteoporosis prophylaxis

Dose

  • In women with a uterus whose last menstrual period occurred over 12 months previously, 1 tablet daily continuously; if changing from cyclical HRT begin treatment at the end of scheduled bleed.

Notes

  1. Prescribe by brand (to aid identification where products contain multiple ingredients, or to prevent confusion where multiple brands contain similar ingredients)
Kliovance®

(Estradiol with norethisterone)

  • Tablets (1mg + 500 microgram) (£4.40)

Indications

  • Menopausal symptoms
  • Osteoporosis prophylaxis

Dose

  • Women whose last menstrual period occurred over 12 months previously, 1 tablet daily continuously; start at end of scheduled bleed if changing from cyclical HRT

Notes

  1. Prescribe by brand (to aid identification where products contain multiple ingredients, or to prevent confusion where multiple brands contain similar ingredients)
  2. Kliovance has lower norethisterone content.
Evorel® Conti

(Estradiol with norethisterone)

  • Patches (50 micrograms/24 hours + 170 micrograms/24 hours) (£13.00)

Indications

  • Menopausal symptoms
  • Osteoporosis prophylaxis

Dose

  • 1 patch to be applied twice weekly continuously

Notes

  1. Prescribe by brand (to aid identification where products contain multiple ingredients, or to prevent confusion where multiple brands contain similar ingredients)

Estradiol with dydrogesterone

Femoston Conti®

(Estradiol with dydrogesterone)

  • Tablets (0.5mg + 2.5mg), (1mg + 5mg) (£8.14)

Indications

  • Menopausal symptoms
  • Osteoporosis prophylaxis (1mg/5mg strength only)

Dose

  • Women whose last menstrual period occurred over 12 months previously, 1 tablet daily continuously (if changing from cyclical HRT begin treatment the day after finishing oestrogen plus progestogen phase)

Notes

  1. Prescribe by brand (to aid identification where products contain multiple ingredients, or to prevent confusion where multiple brands contain similar ingredients)
  2. Femoston Conti is less androgenic
  3. Femoston products are included for patients experiencing progestogenic side effects with the first line agents.

Sequential Combined Preparations (Cyclical HRT)

Estradiol with norethisterone

Elleste Duet®

(Estradiol with norethisterone)

  • Tablets 1mg and (1mg + 1mg) (£3.07)
  • Tablets 2mg and (2mg + 1mg) (£3.07)

Indications

  • Menopausal symptoms
  • Osteoporosis prophylaxis, 2mg tablets only

Dose

  • 1 tablet (estradiol) daily for 16 days starting on day 1 of menstruation (or at any time if cycles have ceased or are infrequent), then 1 tablet (estradiol and norersthisterone) daily for 12 days; subsequent courses are repeated without interval

Notes

  1. Prescribe by brand (to aid identification where products contain multiple ingredients, or to prevent confusion where multiple brands contain similar ingredients)
  2. There are two prescription charges for Elleste Duet

Estradiol with dydrogesterone

Femoston®

(Estradiol with dydrogesterone)

  • Tablets 1mg and (1mg + 10mg) (£5.39)
  • Tablets 2mg and (2mg + 10mg) (£5.39)

Indications

  • Menopausal symptoms
  • Osteoporosis prophylaxis

Dose

  • 1 tablet (estradiol) daily for 14 days, starting within 5 days of onset of menstruation (or any time if cycles have ceased or are infrequent) then 1 tablet (estradiol and dydrogesterone) daily for 14 days; subsequent courses repeated without interval

Notes

  1. Prescribe by brand (to aid identification where products contain multiple ingredients, or to prevent confusion where multiple brands contain similar ingredients)
  2. Femoston is included as a less androgenic alternative allowing dose titration.
  3. Femoston products are included for patients experiencing progestogenic side effects with the first line agents.
  4. There are two prescription charges for Femoston

Selective oestrogen receptor modulators

Raloxifene
  • Tablets 60mg (£8.24)

Indications

  • Secondary prevention of osteoporotic fragility fractures in postmenopausal women

Notes

  1. Raloxifene does not reduce menopausal vasomotor symptoms.
  2. Women taking raloxifene are at increased risk of thromboembolism.
  3. Refer to NICE CG164 (June 2013) for guidance on the use of raloxifene in patients with breast cancer.
  4. NICE TA160: Raloxifene is not recommended as a treatment option for the primary prevention of osteoporotic fragility fractures in postmenopausal women (February 2018)
  5. NICE TA161: Raloxifene is recommended as an alternative treatment option for the secondary prevention of osteoporotic fragility fractures in postmenopausal women (February 2018)

Noretynodrel derivatives (Tibolone)

Tibolone is not suitable for use in the perimenopause or within 12 months of the last menstrual period; women who use such preparations may bleed irregularly in the early stages of treatment—if bleeding continues endometrial abnormality should be ruled out and consideration given to changing to cyclical HRT.

Tibolone
  • Tablets 2.5mg (£10.36)

Indications

  • Short-term treatment of symptoms of oestrogen deficiency (including women being treated with gonadotrophin releasing hormone analogues)
  • Osteoporosis prophylaxis in women at risk of fractures (second-line when other prophylaxis contra-indicated or not tolerated)

Dose

  • 2.5mg daily

Notes

  1. Tibolone is significantly more expensive than first line HRT preparations.
  2. Tibolone combines oestrogenic and progestogenic activity with weak androgenic activity; it is given continuously, without cyclical progestogen.
  3. The benefit-risk balance for tibolone, is described separately to conventional combined HRT. Refer to the September 2007 MHRA drug safety update, the BNF and the manufacturer's summary of product characteristics (SPC) for details.

Progestogens

Progestogens act mainly on tissues sensitised by oestrogens and are used for menstrual disorders including severe dysmenorrhoea and menorrhagia. Although oral progestogens have been used widely for menorrhagia they are relatively ineffective compared to tranexamic acid.

Progestogens have been used for the prevention of miscarriage in women with a history of recurrent miscarriage but there is no evidence of benefit and they are not recommended for this purpose.

Norethisterone
  • Tablets 5mg (£2.03 = 30 tablets)

Indications and dose

  • Endometriosis: 10–15mg daily for 4–6 months or longer, starting on day 5 of cycle (if spotting occurs increase dose to 20–25mg daily, reduced once bleeding has stopped)
  • Dysfunctional uterine bleeding or menorrhagia: 5mg 3 times daily for 10 days to arrest bleeding; 5mg twice daily from day 19 to 26 of cycle to prevent bleeding
  • Dysmenorrhoea: 5mg 3 times daily from day 5 to 24 of cycle, for 3–4 cycles
  • Postponement of menstruation: 5mg 3 times daily starting 3 days before expected onset (menstruation occurs 2–3 days after stopping)

Notes

  1. The norethisterone 5mg preparation is not licensed for HRT
Medroxyprogesterone acetate
  • Tablets 2.5mg, 5mg, 10mg, 100mg, 200mg, 400mg (£2.47 = 5mg x 10)

Indications and dose

  • Oral: 2.5–10mg daily for 5–10 days beginning on day 16 to 21 of cycle, repeated for 2 cycles in dysfunctional uterine bleeding and 3 cycles in secondary amenorrhoea
  • Oral: mild to moderate endometriosis, 10mg 3 times daily for 90 consecutive days, beginning on day 1 of cycle.
  • Doses used for the management of carcinoma are much higher – refer to specialist for guidance.

Progesterone receptor modulators

Ulipristal acetate tablets 5mg

EMA Safety review (March 2020): Suspension of ulipristal acetate for uterine fibroids during ongoing EMA review of liver injury risk.

  • Women should stop taking ulipristal acetate for uterine fibroids while the safety review is ongoing
  • Prescribers should contact patients currently being treated with ulipristal acetate for uterine fibroids as soon as possible and stop their treatment. Consider other treatment options as appropriate
  • Advise patients to immediately report signs and symptoms of liver injury (such as nausea, vomiting, right hypochondrial pain, anorexia, asthenia and jaundice).
  • Liver function testing should be performed 2–4 weeks after treatment has stopped as described in the product information for the medicines.
  • Do not start any new patients on ulipristal acetate for uterine fibroids

Please refer to section 7.3.5 Emergency Contraception for use of ulipristal acetate in emergency contraception (not affected by the EMA safety review)

 

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