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20210930_HRT prescribing supplement

This prescribing supplement has been commissioned and funded by Besins Healthcare (UK) Ltd and developed in partnership with Guidelines. Please see the bottom of the page for full disclaimer.

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Reviewed and co-authored by: Michael Savvas, Consultant Gynaecologist, King’s College Hospital

Oestrogel is indicated for:

  1. Hormone replacement therapy (HRT) for oestrogen deficiency symptoms in postmenopausal women
  2. Prevention of osteoporosis in postmenopausal women at high risk of future fractures who are intolerant of, or contraindicated for, other medicinal products approved for the prevention of osteoporosis.

The experience treating women older than 65 years is limited.

Utrogestan 100 mg is indicated for adjunctive use with oestrogen in postmenopausal women with an intact uterus as HRT.

Foreword: Hormone replacement therapy 

Hormone replacement therapy (HRT) is effective in alleviating the various climacteric symptoms, which include hot flushes, poor sleep, tiredness, mood swings, headaches, and loss of libido.1–3 In the long term HRT can also prevent osteoporosis, reduce the risk of osteoporotic fractures, and reduce the risk of heart disease.2,3

Anxiety remains regarding the risk of breast cancer, which deters many women from taking HRT.2 However, the current evidence is reassuring. The NICE guidelines on menopause state that:

  • HRT with oestrogen alone is associated with little or no change in the risk of breast cancer 
  • HRT with oestrogen and progestogen can be associated with an increase in the risk of breast cancer 
  • any increase in the risk of breast cancer is related to treatment duration and reduces after stopping HRT. 

The increased risk of breast cancer with combined oestrogen and progestogen HRT is small and is less than the risk of breast cancer seen with some avoidable risk factors, such as being overweight or obese.3 The type of progestogen used in combined HRT appears to be important and there is evidence that combined HRT with micronised progesterone for up to 5 years does not increase the risk of breast cancer as seen with synthetic progestogens such as medroxyprogesterone acetate.4,5

There is no evidence that HRT results in an increased mortality from breast cancer. A long-term follow-up study of two randomised trials found that conjugated equine oestrogen (CEE) alone was significantly associated with a lower breast cancer incidence and breast cancer mortality versus placebo.6 CEE plus medroxyprogesterone acetate was significantly associated with a higher breast cancer incidence but no significant difference in breast cancer mortality versus placebo.

Some women are progestogen intolerant, experiencing side effects such as mood changes, headaches, and tiredness, which can limit the use of HRT.7 These side effects are largely seen with the synthetic progestogens; they can be avoided with micronised progesterone.7

More than a quarter (27%) of all deaths in the UK are caused by cardiovascular disease.8 Both combined and unopposed oestrogen replacement have been reported to reduce the incidence and mortality from cardiovascular disease if started before the age of 60 years.

There is an increased risk of venous thromboembolism (VTE) when taking oral HRT (combined or unopposed).9,10 In women using transdermal oestrogen alone, there was no increase in the risk of VTE.9,10 For transdermal HRT combined with a progestogen, the risk of VTE depends upon which progestogen is used; there is no change in VTE risk in women using micronised progesterone.9 Transdermal rather than oral HRT can be prescribed in women who at increased risk of VTE.2

HRT is an effective treatment for menopausal symptoms resulting in improved quality of life. In the long term, the benefits of HRT far outweigh any theoretical risks and the all-cause mortality is reduced in women taking HRT.3 HRT can be prescribed as long as the woman requires it with no arbitrary time limits.3,11

Conflicts of interest 

Michael Savvas declared no conflicts of interest. 

References 

  1. British Menopause Society. Are women suffering in silence? New survey puts spotlight on significant impact of menopause despite recent guideline. BMS press release, 2016. Available from: thebms.org.uk/2016/05/women-suffering-silence-new-bms-survey-puts-spotlight-significant-impact-menopause/
  2. National Institute for Health and Care Excellence. NICE Guideline 23. Menopause: diagnosis and management. Available from: www.nice.org.uk/ guidance/ng23 Last accessed: December 2020. 
  3. Hamoda H, et al. Post Reprod Health. 2020;26(4):181–209. 
  4. Fournier A, et al. Int J Cancer. 2005;114(3):448–454. 
  5. Stute P, et al. Climacteric. 2018;21(2):111– 122. 
  6. Chlebowski R, et al. JAMA. 2020;324(4):369–380. 
  7. Panay N, et al. Hum Reprod Update. 1997;3(2):159–171. 
  8. British Heart Foundation. UK factsheet. BHS, 2020. Available from: www.bhf.org.uk/what-we-do/our-research/heart-statistics
  9. Scarabin P. Climacteric. 2018;21(4):341– 345. 
  10. Vinogradova Y, et al. BMJ. 2019;364:k4810. 
  11. NHS. Hormone replacement therapy. Available from: www.nhs.uk/conditions/ hormone-replacement-therapy-hrt/ Last accessed: December 2020. 

Prescribing hormone replacement therapy (HRT) in postmenopausal women: a focus on Oestrogel® (estradiol) and Utrogestan® 100 mg (micronised progesterone)

 

Individualised approach to HRT 

NICE recommends that prescribers adopt an individualised approach to prescribing HRT through emphasising individual preferences based on an overall balance of indication, short- and long-term benefits, and risks (Box 1).

Box 1: Taking an individualised approach

Menopause and its treatment

  • Explain stages of menopause
  • Identify short-term symptoms
  • Discuss and consider lifestyle changes
  • Discuss benefits and risks of treatments
  • Discuss long-term implications of menopause.

 

Oestrogel and Utrogestan 100 mg 

Oestrogel is a body identical oestrogen transdermal gel that is indicated for oestrogen deficiency symptoms in postmenopausal women.2,3

Utrogestan 100 mg is an oral capsule of body identical micronised progesterone and is indicated for adjunctive use with oestrogen in postmenopausal women with an intact uterus, as HRT.3,4 

Efficacy 

Vasomotor symptoms 

NICE recommends that women should be offered HRT for vasomotor symptoms after discussing with them the short-term and longer-term benefits and risks. Women without a uterus should be offered oestrogen alone. Women with a uterus should be offered oestrogen and progestogen.1

A double-blind, randomised, placebo-controlled study (n=221) showed that Oestrogel significantly reduced the frequency of moderate-to-severe hot flushes at week 12 compared with placebo (82% versus 57% mean reduction, p<0.001, Figure 1) on the starting dose.5,6 Oestrogel was shown to be as effective as oral oestrogen and transdermal oestrogen patches at relieving vasomotor symptoms.7–9

Combining oestrogen with micronised progesterone in women with an intact uterus protected the endometrium from hyperplastic changes associated with oestrogen-only therapy.10 Micronised progesterone plus oestrogen also reduces the number of bleeding days versus medroxyprogesterone acetate plus oestrogen by 23% (over 3 years; p≤0.01).11

Figure 1

Breast cancer 

The overall evidence shows an increased risk of breast cancer in women taking combined oestrogen-progestogen or oestrogen-only HRT that is dependent on the duration of taking HRT. Results from a large meta-analysis showed that after stopping treatment, the excess risk will decrease with time and the time needed to return to baseline depends on the duration of prior HRT use. When HRT is taken for more than 5 years, the risk may persist for 10 years or more.12 Oestrogel and Utrogestan are contraindicated in known, past or suspected breast cancer.2,4

Venous thromboembolism 

HRT is associated with an increased risk of venous thromboembolism (VTE), however transdermal oestrogen does not significantly increase that risk in users when compared to non-users.2,13–18 NICE recommends transdermal rather than oral HRT for menopausal women who are at increased risk of VTE.1 Unlike other progestogens, there is no significant association of VTE with micronised progesterone.4,14,16,19  Oestrogel and Utrogestan are contraindicated in previous or current VTE disorders.2,4

Warnings and precautions 

Please refer to the Oestrogel and Utrogestan 100 mg Summaries of Product Characteristics for the full list of warnings, precautions, contraindications, and adverse events.2,4 

Utrogestan 100 mg contains soya lecithin. As there is a possible relationship between allergy to soya and allergy to peanut, people with soya or peanut allergy should avoid using this medicine.4 For the avoidance of doubt, Utrogestan 100 mg does not contain peanut products. 

How to start a patient on Oestrogel and Utrogestan 100 mg 

Oestrogel

For women who have never taken HRT and are postmenopausal or have very infrequent menstrual cycles, treatment with Oestrogel can be started on any day. For women switching from a continuous oestrogen-progestogen combined HRT, treatment with Oestrogel can be started on any day of the cycle. For women switching from a cyclic or continuous sequential HRT treatment, the patient should finish the therapeutic sequence before beginning treatment with Oestrogel. 

Utrogestan 100 mg

In postmenopausal women with an intact uterus, two regimens of Utrogestan 100 mg are possible based on the bleeding pattern desired: 

  • 100 mg daily at bedtime from day 1 to day 25 of the cycle; withdrawal bleeding is less with this schedule 
  • 200 mg daily at bedtime for 12 days starting on day 15 of the cycle ending on day 26; withdrawal bleeding may occur in the following week. 

Conclusion 

When following menopausal guidelines Oestrogel and Utrogestan 100 mg are body identical options for the management of postmenopausal symptoms in women with an intact uterus.2–4 Separate micronised progesterone allows dose tailoring of the oestrogen component to provide an individualised approach.

References 

  1. National Institute for Health and Care Excellence. NICE Guideline 23. Menopause: diagnosis and management. Available from: www.nice.org.uk/ guidance/ng23 Last accessed: November 2020. 
  2. Oestrogel. Summary of Product Characteristics. Available from www.medicines.org.uk/emc/product/353 Last accessed: September 2021. 
  3. Panay N. Post Reprod Health. 2014;20(2):69–72. 
  4. Utrogestan 100 mg. Summary of Product Characteristics. Available from www.medicines.org.uk/emc/product/352 Last accessed November 2020. 
  5. Archer D, et al. Menopause. 2003;10(6):516–521. 
  6. Archer D, et al. Menopause. 2012;19(6):622–629. 
  7. Dupont A, et al. Maturitas. 1991;13(4):297– 311. 
  8. Jensen P, et al. Maturitas. 1987;9(3):207– 215. 
  9. Akhila Pratapkumar V. Int J Fertil Womens Med. 2006;51(2):64–69. 
  10. The Writing Group for the PEPI Trial. JAMA. 1996;275:370–375. 
  11. Lindenfeld E, et al. Obstet Gynecol. 2002;100(5 Pt 1):853–863. 
  12. Collaborative Group on Hormonal Factors in Breast Cancer. The Lancet. 2019;394(10204):1159–1168.
  13. Sweetland S, et al. J Thromb Haemostasis. 2012;10:2277–2286. 
  14. Canonico M, et al. Circulation. 2007; 115(7):840–845. 
  15. Renoux C, et al. J Thromb Haemost. 2010;8(5):976–986. 
  16. Canonico M, et al. Arterioscler Thromb Vasc Biol. 2010;30(2):340–345. 
  17. Vinogradova Y, et al. BMJ. 2019;364:k4810. 
  18. Mueck A, et al. Climacteric. 2012;15(Suppl 1):11–17. 
  19. Scarabin P, et al. Climacteric. 2018;21(4):341–345.

This prescribing supplement has been commissioned and funded by Besins Healthcare (UK) Ltd and developed in partnership with Guidelines. Besins Healthcare (UK) Ltd suggested the topic and author, and carried out full medical approval on all materials to ensure compliance with regulations. The author did not receive an honorarium for this work. The views and opinions of the author are not necessarily those of Besins Healthcare (UK) Ltd, or of Guidelines, its publisher, advisers, or advertisers. No part of this publication may be reproduced in any form without the permission of the publisher.

OES/2021/041

Date of preparation: October 2021