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®
  • Tablets conjugated oestrogens (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

Estradiol

Elleste solo®
  • Tablets estradiol (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.
Evorel®
  • Patches estradiol (25micrograms, 50 micrograms, 75 micrograms, 100 micrograms per 24 hours) (£4.12 = 75 micrograms)

Indications

  • Menopausal symptoms
  • Osteoporosis prophylaxis

Dose

  1. 1 patch to be applied twice weekly continuously.
  2. 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. 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®
  • Low dose modified release tablets conjugated oestrogen (300 micrograms) and medroxyprogesterone acetate (1.5mg) (£2.17)

Indications

  • Menopausal symptoms

Dose

  • 1 tablet daily, continuously

Notes

  1. Premique® contains medroxyprogesterone and is less androgenic.
  2. Animal source of oestrogen.

Estradiol with norethisterone

Kliofem®
  • Tablets estradiol (2mg), norethisterone (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.
Kliovance®
  • Tablets estradiol valerate (1mg) and norethisterone (500microgram) (£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. Kliovance® has lower norethisterone content.
Evorel® Conti
  • Patches estradiol (50 micrograms/24 hours) and noresthisterone (170 micrograms/24 hours) (£13.00)

Indications

  • Menopausal symptoms
  • Osteoporosis prophylaxis

Dose

  • 1 patch to be applied twice weekly continuously

Estradiol with dydrogesterone

Femoston Conti®
  • Tablets estradiol valerate (0.5mg/1mg) and dydrogesterone (2.5mg/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. Femoston Conti® is less androgenic
  2. Femoston® products are included for patients experiencing progestogenic side effects with the first line agents.

Sequential Combined Preparations (Cyclical HRT)

Conjugated oestrogens with norgestrel

Prempak-C®
  • Tablets conjugated oestrogens (1.25mg) with norgestrel (150 micrograms) (£2.08, £2.47)

Indications

  • Menopausal symptoms
  • Osteoporosis prophylaxis

Dose

  • 1 yellow tablet (oestrogen) daily continuously, starting on day 1 of menstruation (or at any time if cycles have ceased or are infrequent), and 1 brown tablet daily on days 17–28 of each 28-day treatment cycle; subsequent courses are repeated without interval.

Notes

  1. There are two prescription charges for Prempak-C®.
  2. Animal source of oestrogen.

Estradiol with norethisterone

Elleste Duet®
  • Tablets estradiol (1mg, 2mg) with norethisterone acetate (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. There are two prescription charges for Elleste Duet®

Estradiol with dydrogesterone

Femoston®
  • Tablets estradiol (1mg, 2mg) with dydrogesterone (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. Femoston® is included as a less androgenic alternative allowing dose titration.
  2. Femoston® products are included for patients experiencing progestogenic side effects with the first line agents.
  3. There are two prescription charges for Femoston®

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 (£114.13)

Indications

  • Pre-operative treatment of moderate to severe symptoms of uterine fibroids
  • Intermittent treatment of moderate to severe symptoms of uterine fibroids (up to four courses), in line with NICE CG44 (see commissioning policy for more information).

Dose

  • 5mg daily for up to 3 months (maximum) starting during the first week of cycle
  • Re-treatment courses should start at the earliest during the first week of the second menstruation following the previous treatment course completion. Treatment courses should each not exceed 3 months.

Notes

  1. In the case of repeated intermittent treatment, each 12 week course should be initiated by the consultant, who should prescribe the first 28 days' supply. GPs may then be asked to prescribe the remaining 56 days' supply
  2. Periodic monitoring of the endometrium with annual ultrasound (performed after resumption of menstruation during off-treatment period) is recommended with repeated intermittent treatment with UPA 5mg (Esmya SPC). Specialists will be responsible for requesting transvaginal ultrasound if clinically indicated, and acting on the results
  3. Repeated intermittent treatment has been studied up to 4 intermittent courses; the efficacy, safety and cost-effectiveness of more than 4 courses are uncertain
  4. If symptoms return after 4 intermittent courses, the patient should be referred back to a specialist for further consideration of treatment options.

 

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