Unscheduled bleeding on hormone replacement therapy (HRT) is common and a step wise approach based on risk assessment is recommended for management of bleeding.
Let’s look at a case to illustrate this issue.

A 52-year-old postmenopausal woman presents with unscheduled bleeding on HRT. She had her last menstrual period 2 years ago and started HRT for vasomotor and mood symptoms of menopause 8 months ago. She has a body mass index (BMI) of 26 and reports no major previous medical or Gynaecological problems other than endometriosis for which she had a laparoscopic surgery 15 years ago.
She has been using transdermal oestrogen gel and natural micronised progesterone (100mg) orally daily for HRT. She started experiencing breakthrough bleeding about 6 weeks into starting her HRT and it has been continuing irregularly for past 6 months. She is worried about the bleeding but prefers not to stop the HRT as it has significantly improved her quality of life.

What is unscheduled bleeding on HRT? And what should be the next steps for this patient?

Unscheduled bleeding is a common problem, affecting up to about 40% of women using cyclical or continuous combined hormone replacement therapy. It is a major factor leading to repeat consultations and cessation of HRT^5,10,11. Unscheduled bleeding is defined as irregular bleeding that occurs more than six months after either initiating HRT or, changing the preparation or dose in women established on HRT. When women present with unscheduled bleeding on HRT, assessment starts with a comprehensive clinical assessment comprising of a thorough patient history, assessment for compliance/missed doses, individual risk factors for cancer and abdominal or pelvic examination as necessary including speculum examination and swabs^8,9.

As has been the experience of this patient, irregular or unscheduled bleeding remains a common side effect of HRT particularly in the first few months after starting or changing HRT preparation despite good compliance. This patient took her HRT medications regularly and a speculum examination did not reveal any abnormal findings related to cervical or vaginal tissues.

While often not a cause for concern, persistent or concerning bleeding warrants investigation⁹. The British Menopause Society⁹ has produced a guideline on the topic and advises healthcare professionals to assess the bleeding pattern, HRT type and dosage, and individual risk factors for endometrial cancer when deciding about management. Investigations for unscheduled bleeding can include a pelvic ultrasound, endometrial biopsy, and endometrial assessment via hysteroscopy (individualised based on clinical findings and clinical resources). Adjusting HRT dosage or type is often necessary to manage bleeding, aiming to balance oestrogen and progestogen levels^5,8,9,11.

Timeframes for investigating –
Within 6 months of initiating HRT unscheduled bleeding is common or within 3 months of a dose or preparation change.
Beyond 6 months: Bleeding occurring after 6 months on HRT, or persistent bleeding after 3 months of a dose change, should be investigated⁹

When to be concerned?

• Heavy or prolonged bleeding on sequential HRT (e.g., bleeding most days of the month or prolonged withdrawal bleeds).
• Heavy, painful, or post-coital bleeding.
• Bleeding associated with other worrying symptoms.
• If unscheduled bleeding continues in low-risk women, after six months of adjustments, discuss the options of an urgent ultrasound (within six weeks) versus weaning off HRT and consideration of non-hormonal alternatives (to avoid invasive investigations).
• Offer an urgent TVS (within 6 weeks) if the first presentation with bleeding occurs more than six months after initiating, or three months after changing, the HRT preparation.
• Offer an urgent TVS (within 6 weeks), irrespective of interval since starting, or changing, HRT preparations if a) bleeding is prolonged / heavy or, b) there are 2 minor risk factors for endometrial cancer.
• Offer an urgent suspicion of cancer pathway (USCP) referral to women with one major or three minor risk factors for endometrial cancer – irrespective of bleeding type or interval since starting or changing HRT preparations. Adjustments to the progestogen, or stopping HRT, should be offered whilst awaiting assessment⁹

So, what was the action for this patient?

As this patient had persistent bleeding more than 6 months since starting HRT, she was referred for a transvaginal ultrasound. The scan revealed normal findings with an endometrial thickness of 3.3 mm and no focal pathology. Her HRT was changed by increasing her oral progesterone dose to 200 mg daily after explaining the benefits versus risks. She went on to continue to have persistent unscheduled bleeding on HRT despite the change in HRT and had further scan after 3 months which did not reveal any abnormal findings. She then switched to an oral fixed dose combination of oestrogen and dydrogesterone (Femoston Conti) and the breakthrough bleeding stopped after 2 months. The patient was counselled about benefits versus side effects/risks of oral HRT in the long-term (as well as other alternatives) and she chose the option to continue with it.

How can we make sure we minimise unscheduled bleeding on HRT for our patients?

Educate patients about what may constitute normal bleeding on HRT and when to seek medical advice^5,8,9,11.
Individualised management is important:
HRT should be tailored to the individual’s needs and response to treatment. When endometrial pathology is ruled out, generally, increasing the progestogen dose within license or changing its type usually stops the bleeding⁵. Lowering oestrogen dose can also help. Switching to fixed dose combinations such as oral combined HRT (when there is no underlying thrombosis risks) can also encourage better compliance and help stop bleeding. Traditional progestogens such as medroxyprogesterone⁶ and norethisterone⁷ or dydrogesterone^1,2,3,4 appear to be more effective at bleeding-control than micronised progesterone²². Intrauterine progestogen coils or cyclical HRT preparations can be a more effective way of managing bleeding especially during perimenopause with background hormone fluctuations⁹. It is important that healthcare providers follow the guidance provided by British Menopause Society and their local healthcare body to make sure that unscheduled bleeding is investigated promptly and appropriately based on a risk-factor approach balancing both unnecessary over-intervention versus missing a significant pathology.

What is Femoston range of HRT?

Femoston® is indicated for oestrogen deficiency symptoms in postmenopausal women at least 6 months since the last menstrual cycle^1-2.
Whilst Femoston®-conti is indicated for oestrogen deficiency symptoms in postmenopausal women at least 12 months since their last menstruation^3-4.
Femoston® oral HRT is available in 4 preparations^1-4:
Two are cyclical combined HRT types – Femoston® 1/10 and 2/10mg. These provide the women with daily 1 or 2 mg oral oestradiol for 28 days and dydrogesterone 10 mg daily for 14 out of 28 days. This form of HRT induces monthly withdrawal bleeds.
The other two are Femoston®-conti and Femoston®-conti ultra-low dose, which ae continuous combined bleed-free HRT types providing 0.5-1mg oestradiol and 2.5-5mg dydrogesterone daily respectively.

It is generally recommended that cyclical HRT should be switched to bleed-free HRT anywhere between 1-5 years of using cyclical HRT – this is because the use of cyclical HRT beyond 5 years can slightly increase the chance of endometrial pathology such as hyperplasia in women above the age of 45.
Femoston® combines oestradiol with dydrogesterone, a progesterone closely comparable to endogenous progesterone^1-4.
This offers efficacy without oestrogenic and androgenic side effects^1-4.

Femoston® provides a wide dose range from standard to ultra-low. All are once-daily, fixed dose oral tablets for ease of use^1-4.

• Femoston demonstrated endometrial protection with more than 98% of 442 women studied showing adequate progestational response all with an acceptable bleeding profile^12-14.
• Femoston was not associated with higher risk of cardiovascular events compared to other HRT* as shown in an assessment of the risk of developing myocardial infarction, thrombotic stroke or venous thromboembolism in estradiol/dydrogesterone users (n=4,658), users of other HRT(n=30,048), or non-users of HRT (n=34,706) using data from the General Practice Research Database (GPRD)¹⁵.
• Lower breast cancer16-19 and VTE20 risk associated with dyrdrogesterone, the progesterone found in Femoston, vs other synthetic progestogens including NETA, MPA and levonorgestrel.
• Breast Cancer – as per IMS recommendations, based on three studies showing that micronised progesterone or dydrogesterone could be associated with a lower risk than synthetic progesterone, a large European observational study, a case-control study in France and a Finish registry study¹⁷
• VTE – assessment of the association between risk of venous thromboembolism and use of different types of HRT as calculated from QResearch and Clinical Practice Research Datalink (CPRD) database records of 80,395 women aged 40-79 with a primary diagnosis of VTE between 1998 and 2017²⁰.
• Femoston®-conti was found to significantly improve vasomotor symptoms versus placebo. A study of 313 women experiencing >50 moderate to severe hot flushes during the previous week, randomised to Femoston-conti 0.5/2.5mg or 1/5mg treatment arms or placebo for 13 weeks, assessed for the reduction in the number of moderate to severe hot flushes/day. Both 0.5/2.5mg and 1/5mg doses were well tolerated²¹.
• Femoston®-conti 1/5mg, Femoston®1/10mg and 2/10mg are also indicated for prevention of osteoporosis in postmenopausal women at high risk of fractures who are intolerant of, or contraindicated for, other medicinal products approved for the prevention of osteoporosis^1,2,4.
• High rates of amenorrhoea were achieved, even at ultra-low dose. A randomised control trial assessing the percentage of women with amenorrhoea 3 months and 10-12 months post initiation showed 91% of study participants receiving Femoston®-conti 0.5/2.5mg (n=122) and 81% receiving 1/5mg (n=59) achieved amenorrhoea²¹.

*other HRT= oral conjugated equine oestrogen (CEE) + norgestrel, oral oestradiol (valerate) + norethisterone (acetate), or oral CEE + medroxyprogesterone acetate.

Abbreviations:
IMS, International Menopause Society; HRT, hormone replacement therapy; MPA, medroxyprogesterone acetate; NETA, norethisterone acetate; VTE, venous thromboembolism

References:
1. Femoston 1/10mg Summary of Product Characteristics
2. Femoston 2/10mg Summary of Product Characteristics
3. Femoston- Conti 0.5/2.5mg Summary of Product Characteristics
4. Femoston- Conti 1/5mg Summary of Product Characteristics
5. BMS Progestogens and endometrial protection; Accessed July 2025
6.Medroxyprogesterone Summary of Product Characteristics
7. Norethisterone Summary of Product Characteristics
8. NICE Menopause identification and management; Accessed August 2025
9. Management of unscheduled bleeding on hormone replacement therapy
10. Binkowska M et al. Prz Menopauzalny 2015 Jun 22;14(2):134–143
11. BMS NICE Menopause diagnosis and management Guideline to practice; Accessed August 2025
12. Ferenczy A et al; Climacteric 2002; 5(1): 26-35
13. Quereux C et al Maturitas; Maturitas 2006; 53(3): 299-305
14. Bergeron C et al; Maturitas 2010; 66(2): 201-5
15. C Schneider, S S Jick, C R Meier; 2009 Oct;12(5):445-53
16. Fournier A, et al. Breast Cancer Res Treat. 2008; 107:103–11
17. Baber RJ, Panay N, Fenton A; IMS Writing Group. Climacteric. 2016 Apr;19(2):109-50
18. Collaborative Group on Hormonal Factors in Breast Cancer. The Lancet. 2019; 394(10204): 1159–68.8
19. Vinogradova Y, BMJ 2020 Oct 28:371:m3873
20. Vinogradova Y, et al. BMJ. 2019; 364: k4810
21. Stevenson JC, et al; Maturitas. 2010 Nov;67(3):227-32
22. Shoupe D. 2021. Contracept Reprod Med. 7;6:3

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