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Hormone replacement therapy (HRT) shortage: switching to Femoston®  (estradiol / dydrogesterone) from an alternative combination oral or transdermal HRT

Reviewed and endorsed by:

Dr John C Stevenson, Consultant Physician and Endocrinologist, Royal Brompton Hospital; Reader in Metabolic Medicine, Imperial College London

Dr Sarah Gray, GP specialist in Women’s Health, St Erme Medical, Cornwall

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Introduction

During the supply constraint of hormone replacement therapy (HRT), prescribers must consider all the alternative options available, which may involve a change in route of administration and the progestogen.

Femoston® and Femoston® conti contain oestradiol and dydrogesterone, and are suitable oral alternatives in women for whom oral therapy is not contraindicated.

Indication

Femoston® 1/10 and 2/10 are indicated for oestrogen deficiency symptoms in postmenopausal women at least 6 months since last menses.1

Femoston® conti 0.5/2.5 and 1/5 are indicated for oestrogen deficiency symptoms in postmenopausal women at least 12 months since last menses.2

Switching route of administration: transdermal to oral

The British Menopause Society and NICE guidelines recommend transdermal rather than oral HRT for menopausal women who are at increased risk* of venous thromboembolism (VTE).3,5

The baseline population risk of VTE is relatively low, at 16 per 10,000 women (aged 50–59 years) years, and the addition of standard dose oral HRT increases the risk by nine per 10,000 women years.6

In regard to breast cancer risk, observational studies have demonstrated that there are no differences between routes of administration.7,8

Individualised approach

When individualising treatment for menopausal women, the NICE guideline also highlight the importance of considering the woman’s personal choice and preferences.3

Switching progestogen to dydrogesterone

Progestogens are required for non‑hysterectomised women for endometrial protection; various progestogens are used in combined HRT, and they may display different side-effects and risk profiles.

Breast cancer

Overall evidence suggests an increased risk of breast cancer diagnosis in women taking combined HRT.1,2

However, recent evidence suggests that different progestogens may have different risk profiles. Observational studies have shown that oestradiol plus dydrogesterone may be associated with a lower risk of breast cancer diagnosis than some other preparations (Figure 1).7,9

Graph 1 Femoston

Picture 1: Standard incidence ratio of invasive breast cancer among women using estrogen-progestogen therapy between 1994 and 2005

Venous thromboembolism

HRT is associated with a 1.3–3 fold risk of developing VTE. The occurrence of such an event is more likely in the first year of HRT than later.1,2

The occurrence of VTE associated with Femoston® and Femoston® conti is uncommon (between 1/100 and 1/1,000).1,2 Observational studies suggest that dosage, route of administration, and types of oestrogen and progestogen may impact the associated VTE risk.6,10,11 A recent case control study suggested that HRTs containing oestradiol and dydrogesterone were associated with a lower VTE risk profile compared to other oral combined HRTs.6

Graph 2 Femoston

Picture 2: Odds ratio of VTE for different types of oral HRT

Conclusion

During the shortage of HRT, prescribers must consider all options available to women, and Femoston® and Femoston® conti are viable alternatives to other transdermal and oral HRTs.

The overall baseline risk of VTE is low, and oral HRT may be a suitable alternative for women without additional risk factors for VTE, and some may even consider this to be a more convenient option.

Observational studies have demonstrated that the combination of oestradiol and dydrogesterone (Femoston® and Femoston® conti) may be associated with a lower breast cancer and VTE risk compared to other preparations, and therefore should be considered as a suitable alternative.

* Risk factors for VTE include:3,4 previous VTE, obesity, strong family history, major surgery, multiple trauma, immobilisation, increasing age, thrombophilia (e.g. Factor V Leiden), malignancy.

References

  1. Mylan. Femoston®—summary of product characteristics. November 2016. www.medicines.org.uk/emc/search?q=femoston
  2. Mylan. Femoston®-conti—summary of product characteristics. June 2019. www.medicines.org.uk/emc/search?q=femoston+conti
  3. NICE. Menopause: diagnosis and management. NICE Guideline 23. NICE, 2015. Available at: www.nice.org.uk/ng23
  4. Anderson F Jr, Spencer F. Risk factors for venous thromboembolism. Circulation 2003; 107  (23 suppl 1): I9–I16.
  5. Hamoda H, Panay N, Arya R et al. The British Menopause Society & Women’s Health Concern 2016 recommendations on hormone replacement therapy in menopausal women. Post Reproductive Health 2016; 22 (4): 165–183.
  6. Vinogradova Y, Coupland C, Hippisley-Cox J. Use of hormone replacement therapy and risk of venous thromboembolism: nested case-control studies using the QResearch and CPRD databases. BMJ 2019; 364: k4810.
  7. Lyytinen H, Pukkala E, Ylikorkala O. Breast cancer risk in postmenopausal women using estradiol progestogen therapy. Obstet Gynecol 2009; 113 (1): 65–73.
  8. Collaborative Group on Hormonal Factors in Breast Cancer. Type and timing of menopausal hormone therapy and breast cancer risk: individual participant meta-analysis of the worldwide epidemiological evidence. Lancet 2019; 394 (10204): 1159–1168.
  9. Fournier A, Berrino F, Clavel-Chapelon F. Unequal risks for breast cancer associated with different hormone replacement therapies results from the E3N cohort study. Breast Cancer Res Treat 2008; 107 (1): 103–111.
  10. Canonico M, Oger E, Plu-Bureau G et al. Hormone therapy and venous thromboembolism among postmenopausal women: impact of the route of estrogen administration and progestogens: the ESTHER study. Circulation 2007; 115 (7): 840–845.
  11. Schneider C, Jick S, Meier C. Risk of cardiovascular outcomes in users of estradiol/dydrogesterone or other HRT preparations. Climacteric 2009; 12 (5): 445–453.

This supplement has been commissioned and funded by Mylan and developed in partnership with Guidelines. Mylan suggested the topic and carried out full medical approval on all materials to ensure compliance with regulations. The sponsorship fee included honoraria for Dr Stevenson and Dr Gray. The views and opinions presented are not necessarily those of Guidelines, its publisher, advisers, or advertisers. No part of this publication may be reproduced in any form without the permission of the publisher.

FEM-2019-0098

Date of preparation: November 2019