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View Femoston® (estradiol/dydrogesterone) and Femoston® -conti (estradiol/dydrogesterone) prescribing and adverse event reporting information.

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Guidance background 

  • Hormone replacement therapy (HRT) is first-line treatment for menopausal symptoms:1–3
    • although all forms of systemic HRT have proven benefits in terms of vasomotor symptom control, other risk–benefit profiles depend on the type of HRT regimen and the woman’s characteristics2,4 
    • the current NICE guideline on menopause management (NG23) recommends an individualised approach for diagnosing and treating women with menopausal symptoms based on their specific needs1
  • Little guidance is currently available on prescribing the progestogen component of combined HRT:
    • an expert panel was established to identify the different progestogens used in HRT that are available in the UK; their formulations and delivery routes; and their profiles in terms of breast cancer and venous thromboembolism (VTE) risk, metabolic effects, and side effects 
    • this guidance focuses on use of the combined preparation containing oestradiol plus the progestogen, dydrogesterone (Femoston® and Femoston® -conti) for menopausal women with an intact uterus, who are suitable for oral HRT and have no pre-existing increased risk of VTE or breast cancer. 

When to use HRT 

  • Prescribe HRT for women:
    • to treat vasomotor symptoms after discussing with them the short-term (up to 5 years) and longer-term benefits and risks1
    • to prevent osteoporosis in women with premature ovarian insufficiency (POI) and to be used until at least the age of natural menopause1
    • to prevent osteoporosis as a second line agent in menopausal women <60 years, particularly in those with oestrogen deficiency symptoms1,4,6 
    • with oestrogen deficiency symptoms post-hysterectomy (those with endometriosis should be prescribed a continuous combined HRT for the first few years after surgery5
    • with menopausal symptoms, including premenstrual symptoms, anxiety, memory problems and difficulty concentrating (brain fog), and mood disturbances1,2,4
      • women who present with psychological symptoms may also have undisclosed symptoms of hot flushes and night sweats 
  • No specific blood tests are required before starting HRT. It is good practice to document blood pressure (BP) and body mass index (BMI) at baseline, women should be breast aware and attend check ups with the NHS Breast Cancer Screening Programme (depending on age)
    • diagnose menopausal symptoms without blood tests in otherwise healthy women >45 years with typical symptoms 
    • consider FSH levels in women aged 40–45 years with menopausal symptoms or changes in their menstrual cycle, and in women <40 years in whom menopause is suspected.1

Adding a progestogen to oestrogen 

  • The addition of a progestogen greatly reduces the risk of oestrogen-associated endometrial hyperplasia in non-hysterectomised women6–9 
  • Progestogen-containing HRT should therefore be used in women with an intact uterus (including women with suspected residual endometrium after subtotal hysterectomy, after endometrial ablation, and in women with endometriosis and possible residual endometriosis lesions)5
  • A variety of progestogens are available for combined HRT:
    • Table 1 summarises the progestogens available to prescribe as part of HRT in the UK 
    • dydrogesterone is the progestogen in the oral HRT combinations Femoston® and Femoston®‑conti.6–9

Table 1

Risk-based selection of progestogen-containing HRT formulations 

  • Good history is key to selecting the optimal HRT for each patient:
    • The Primary Care Women’s Health Forum has produced a guide to support provision of HRT through telephone and virtual consultations (see Useful resources box) 
  • The main risks associated with HRT are breast cancer and VTE. Although these are very uncommon, they may vary depending on the type of progestogen combination (Table 2 and Table 3)
    • when selecting progestogen-containing HRT consider patient’s individual benefits and risks profile, including whether they have a uterus, their risk factors for breast cancer, VTE, and cardiovascular disease (including BMI) 
    • the lowest effective dose of HRT for the individual should be chosen following informed discussion with the patient.4

Breast cancer and progestogens 

  • A personal history of breast cancer is a contraindication to HRT. For those with no personal history of breast cancer, but have a concerning family history, seek specialist secondary care advice1,10
    • 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 HRT use6–9
      • the Women’s Health Initiative (WHI) study and a meta-analysis from 2019 are consistent in finding an increased risk of breast cancer in women taking combined oestrogen-progestogen for HRT that becomes apparent after about three (range 1–4) years6–9 
    • the progestogen component of combined HRT has a differential effect on the risk of breast cancer:
      • observational studies have shown that oestradiol + dydrogesterone may be associated with a lower risk of breast cancer diagnosis than some other combined progestogen preparations2,4,11–14
        • the rate of increased breast cancer risk with HRT differs by type of progestogen used 
        • dydrogesterone appears to increase this risk at a slower rate than some other progestogen preparations (Figure 1)14
    • consider seeking specialist advice if breast cancer risk is a particular concern.

VTE and progestogens 

  • The risk of VTE is increased by oral HRT preparations. Transdermal HRT at standard doses does not increase this risk1
    • the type of progestogen can differentially affect the risk of VTE with micronised progesterone and dydrogesterone conferring a lower risk compared to that with other synthetic progestogens4
    • in a large UK based case-control study conducted in 2019; amongst the oral combined preparations oestradiol with dydrogesterone was associated with the lowest risk of VTE 1.18 (0.98 to 1.42, Table 3 and Figure 2).15

Table 2

Table 3

Figure 1

Figure 2

Metabolic effects of different progestogens 

  • For overweight women and those with type 2 diabetes or prediabetes, consider the metabolic effects of different progestogen-containing HRTs:,21
    • oestradiol + dydrogesterone may have metabolic advantages over other combinations in terms of insulin resistance and lipid profiles19–21
      • oestrogen increases HDL, but this beneficial effect is blunted by medroxyprogesterone acetate and norethisterone acetate19,21 
        • this blunting effect is not seen with dydrogesterone (Figure 3)19,21
      • oestrogen reduces insulin resistance, but the beneficial effect of the oestrogen on insulin sensitivity may be blunted by the addition of a progestogen21,22
        • dydrogesterone has a neutral effect on glucose metabolism, and may be considered to be used in women with insulin resistance or diabetes21
    • Randomised controlled trials have found no difference in weight gain between placebo and HRT23
      • differences between progestogens in terms of weight gain are not known.

Figure 3

Endometrial hyperplasia and progestogens

  • The addition of a progestogen to oestrogen greatly reduces the risk of endometrial
    • women with a history of endometriosis should receive continuous combined HRT for at least the first few years after surgery, or until asymptomatic before moving onto oestrogen-replacement therapy5
    • the risk of endometrial hyperplasia with progestogen-containing HRT is higher when progestogen is given for fewer than 10 days.24,25

Side effects and progestogens

  • Side effects differ for androgenic and non-androgenic progestogens due to their differential effects on steroid receptors:
    • norethisterone acetate, levonorgestrel, and medroxyprogesterone acetate are androgenic and result in side effects such as acne, greasy skin, and hirsutism16,17
    • dydrogesterone and micronised progesterone are non-androgenic and do not produce these side effects (Table 2) and should be considered in patients prone to acne or with a history of polycystic ovarian syndrome
    • micronised progesterone can cause drowsiness, which is not reported with

Other considerations

  • Lifestyle and behavioural factors should be taken into account when choosing the route of delivery. For example:
    • consider transdermal HRT in those who choose it as an option, where there is poor symptom control with oral HRT, gastrointestinal (GI) disorder affecting oral absorption, previous history of VTE, BMI >30, migraines, current use of hepatic medication (inducing enzymes), and gall bladder disease
    • oral HRT may be preferred in younger women who do not smoke.

Selecting the regimen and dose for Femoston® and Femoston® -conti

  • Oestrogen + dydrogesterone is available as sequential (Femoston®)6,7 or continuous combined (Femoston® -conti)8,9
  • Figure 4 provides an algorithm to guide prescribing of the Femoston® range 
  • Boxes 1 and 2 illustrate key questions when selecting hormone therapy, patient considerations before and during HRT.

Sequential HRT with Femoston®

  • Use sequential HRT for:
    • oestrogen deficiency symptoms in postmenopausal women at least 6 months since last menses6,7
  • Initial dose selection should be Femoston® 1/10. However, other factors should also be taken into consideration when choosing the starting dose: 
    • for women with POI (aged <40 years), a higher dose may be required such as Femoston® 2/10
    • for women sensitive to oestrogens, start with Femoston® 1/10
    • for women with severe symptoms, start the higher dose of Femoston® 2/10
    • for women who have been oestrogen deficient for some time, start with the lower dose of Femoston® 1/10
  • Advise women that side effects are likely to have settled by 3 months. 

Continuous combined HRT with Femoston® -conti

  • Use continuous combined HRT for:
    • women with established menopause, whose last period was more than 12 months ago 
  • Initial dose selection can be based on the woman’s age:
    • for women <60 years, start with the higher dose of Femoston® -conti 1/5
    • for women >60 years, start with the lower dose of Femoston® -conti 0.5/2.5
  • Advise women that side effects are likely to have settled by 3 months. 

Figure 4

Box 1 and 2

Monitoring and follow up

  • Monitoring of oestrogen levels is generally not required while taking HRT 
  • Review the patient after 3 months
    • check whether symptoms are controlled and whether any side effects have settled 
      • increase the dose after 3 months if symptom relief with the lower dose is insufficient 
      • if side effects are troublesome, taper down the dose rather than stopping HRT completely 
      • if women still experience vaginal atrophy or dryness, prescribe a vaginal oestrogen in addition 
    • check BP
      • BP increase is uncommon with HRT 
    • reduce the dose if the patient develops breast tenderness
  • HRT prescribing is generally reviewed three months after initiation then on an annual basis. Frequency of review depends on individual clinical need. There are no arbitrary limits to the duration of use. Treatment should be guided by the balance of the benefits and risks for each individual patient 
    • consider reducing the dose of HRT once women turn 60 years of age.

Switching from sequential to continuous combined therapy

  • After 1–2 years, consider switching women on sequential HRT to continuous combined therapy:
    • for each woman, the increased endometrial protection with continuous combined HRT must be balanced against the slightly increased risk of breast cancer
    • patient preference should be considered when switching from sequential to continuous combined therapy: 
      • some women may prefer to remain on sequential therapy to maintain their monthly bleed, while others may prefer the amenorrhoea with continuous combined 
  • Start on continuous combined therapy after the withdrawal bleed 
    • women may experience spotting or bleeding during the first few months after the switch:
      • if bleeding persists, consider switching back to sequential or reduce the oestrogen dose
      • refer women whose bleeding becomes heavy and/or painful or who start bleeding after 6 months of amenorrhoea to a gynaecologist for investigations
  • Taper down the dose in women who want to stop HRT rather than stopping abruptly, unless treatment is being withdrawn due to a major event such as VTE.



  1. NICE. Menopause: diagnosis and management. NICE Guideline 23. NICE, 2015 (last updated December 2019). Available at: www.nice.org.uk/guidance/ng23
  2. Baber R et al. IMS Writing Group. 2016 IMS Recommendations on women’s midlife health and menopause hormone therapy. Climacteric. 2016; 19(2): 109–50. 
  3. British Menopause Society. HRT–Guide. BMS, 2020. Available at: www.thebms.org.uk/wp-content/uploads/2020/07/04-BMS-TfC-HRT-Guide-JULY2020-01D.pdf
  4. Hamoda H et al. The British Menopause Society & Women’s Health Concern 2020 recommendations on hormone replacement therapy in menopausal women. Post Reproductive Health. October 2020.
  5. British Menopause Society. Induced menopause in women with endometriosis. BMS, 2019. Available at: https://thebms.org.uk/publications/tools-for-clinicians/induced-menopause-in-women-with-endometriosis/
  6. Femoston® 1/10 mg—summary of product characteristics. September 2020. www.medicines.org.uk/emc/product/5523
  7. Femoston® 2/10 mg— summary of product characteristics. September 2020. www.medicines.org.uk/emc/product/3903
  8. Femoston® -conti 0.5 mg/2.5 mg— summary of product characteristics. August 2020. www.medicines.org.uk/emc/product/2825
  9. Femoston® -conti 1 mg/5 mg— summary of product characteristics. August 2020. www.medicines.org.uk/emc/product/1347
  10. NICE. Familial breast cancer: classification, care and managing breast cancer and related risks in people with a family history of breast cancer. Clinical Guideline 164. NICE 2013 (last updated November 2019) Available at: www.nice.org.uk/guidance/cg164
  11. Lyytinen H, Pukkala E, Ylikorkala O. Breast cancer risk in postmenopausal women using estradiol-progestogen therapy. ObstetGynecol. 2009; 113(1): 65–73. 
  12. 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; 29 Aug. Available at: www.thelancet.com/journals/lancet/article/PIIS0140-6736(19)31709-X/fulltext
  13. 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: 103–111. 
  14. Vinogradova Y, Coupland C, Hippisley-Cox J. Use of hormone replacement therapy and risk of breast cancer: nested case-control studies using the QResearch and CPRD databases. BMJ 2020; 371: m3873
  15. 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. 
  16. Schindler AE et al. Classification and pharmacology of progestins. Maturitas, 2008; 61(1–2): 171–180.
  17. Panay N, Studd J. Progestogen intolerance and compliance with hormone replacement therapy in menopausal women. Hum Reprod Update. 1997 Mar-Apr; 3(2): 159–71.
  18. Utrogestan 100mg Capsules—summary of product characteristics. October 2020. www.medicines.org.uk/emc/product/352
  19. Godsland, et al. Effects of postmenopausal hormone replacement therapy on lipid, lipoprotein and apolipoprotein(a) concentrations: analysis of studies published from 1974-2000. Fertil Steril. 2001; 75(5): 898–915.
  20. Stevenson J et al. 1 and 2 mg 17beta-estradiol combined with sequential dydrogesterone have similar effects on the serum lipid profile of postmenopausal women. Climacteric, 2005 Dec; 8(4): 352–9.
  21. Stevenson JC et al. Progestogens as a component of menopausal hormone therapy: the right molecule makes the difference. Drugs Context. 2020 Dec 2; 9: 2020-10-1.
  22. Lindheim SR et al. A possible bimodal effect of estrogen on insulin sensitivity in postmenopausal women and the attenuating effect of added progestin. Fertil Sieril. 1993; 60: 664–667.
  23. van Seumeren I. Weight gain and hormone replacement therapy: are women’s fears justified? Maturitas, 2002; 34(1): S3–8.
  24. Weiderpass E et al. Risk of endometrial cancer following estrogen replacement with and without progestins. J Natl Cancer Inst, 1999; 91(13): 1131–7. 
  25. Brinton LA, Felix AS. Menopausal hormone therapy and risk of endometrial cancer. J Steroid Biochem Mol Biol. 2014; 142: 83–9.


This promotional algorithm has been commissioned and funded by Viatris and developed in partnership with Guidelines. Viatris reviewed and approved the scope and pre-meeting documents, suggested a Chair and experts for the group, and carried out full medical approval on all materials to ensure compliance with regulations. Viatris staff also attended the development meeting. Viatris contracted the participants and paid their honoraria. The views and opinions of the participants are not necessarily of Viatris, Guidelines, its publisher, advisers, or advertisers. No part of this publication may be reproduced in any form without the permission of the publisher.

Group members–Professor John Stevenson (Chair), Professor Serge Rozenberg, Dr Diana Mansour, Dr Joanne Hobson.


Job code: FEM-2021-0237

Date of preparation: June 2021