Bleeding on HRT - information for women who still have a womb

When a woman still has a uterus (womb) the endometrium (womb lining) responds to both of the female hormones oestrogen and progesterone, and depending on what is happening with these hormones this can result in menstrual bleeding. In the normal menstrual cycle the endometrium thickens under the influence of oestrogen, becomes ready for implantation under the influence of progesterone, and then sheds when progesterone levels drop if no pregnancy occurs - this is a normal period.

HRT is always given with the same dosage of oestrogen every day, but can either be given with the same dosage of progesterone (called continuous) or with 2 weeks of progesterone and 2 weeks without progesterone (called sequential). Progesterone must be part of an HRT regime otherwise unopposed oestrogen can causes abnormal cells to develop, and ultimately lead to endometrial cancer. Women should be offered continuous HRT if they have not had a natural period for 12 months, they are aged 54 or over or they have had 5 years of sequential HRT (after the age of 45).

A continuous regime would ideally result in no vaginal bleeding, whereas a sequential regime will usually result in monthly bleeds. 85% women on sequential HRT will get some bleeding, and to be considered ‘normal’ this should be light, short in duration and occurring when they are not taking any progesterone.

Bleeding patterns can be outside of this ‘norm’, and is called ‘unscheduled’, and determining when this needs to be investigated further is important. The most important condition which needs to be detected is endometrial cancer, which typically presents with abnormal vaginal bleeding. Major risks factors for endometrial cancer are:

1) BMI ≥ 40

2) hereditary conditions such as Lynch or Cowden syndrome.

Minor risk factors include:

1) BMI 30-39

2) diabetes

3) polycystic ovarian syndrome (PCOS).

Non-cancerous causes like polyps or fibroids should also be considered. Irregular bleeding is common and it is felt that up to 50% of women may discontinue HRT use due to unscheduled bleeding.

Unscheduled bleeding

All women should be offered a referral under the 2 week wait cancer referral pathway if they have 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 assessment.

All women should be offered an ultrasound scan within 6 weeks if they have 2 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 assessment.

All women should be offered an ultrasound scan within 6 weeks if the first presentation with bleeding occurs more than six months after initiating, or three months after changing, the HRT preparation.

Sequential HRT

With sequential HRT up to 40% of women will experience irregular bleeding, and for some women this is troublesome enough for them to want to stop HRT. More than 5 years of sequential HRT in postmenopausal women (ie for 5 years after the last natural period) is associated with a three-fold increase in endometrial cancer risk whereas continuous combined progestogen was associated with a four- to five-fold reduction in cancer risk; it is important to note that is not relevant to peri-menopausal women. It is therefore important to switch from a sequential to a continuous regime by the age of 54. Timing a switch earlier than this can be challenging but it is recommended that this be trialled after 5 years of continuous use if started over the age of 45, and this is particularly likely to be successful if there hasn’t been any withdrawal bleeding.

Potential problems within 6 months of starting HRT or 3 months of changing the dosage or preparation:

• Withdrawal bleed is heavy or prolonged

  • An ultrasound scan should be arranged within 6 weeks

  • If the scan is normal then treatment options include to increase the dose or change the type of progestogen (Mirena coil is the least likely to cause unscheduled bleeding) or reduce the dose of oestrogen or stop HRT

• Bleeding occurs early in the progestogen phase

  • Increase the dose or change the type of progestogen (Mirena coil is the least likely to cause unscheduled bleeding)

• Spotting before the withdrawal bleed (spotting is defined as bleeding not requiring any sanitary towel, or not more than one per day)

  • Increase the dose of oestrogen

If these changes do not result in a cessation of unscheduled bleeding after 6 months of starting HRT or 3 months of changing the dosage/preparation then it is recommended to either stop HRT and organise an ultrasound if bleeding does not cease after 4 weeks, or organise an ultrasound scan within 6 weeks.

Combined HRT

With combined HRT, up to 80% of women will experience unscheduled bleeding or spotting in the first 6 months of treatment. It is important to emphasise that 10-20% of women will still experience vaginal bleeding on combined HRT if it is given transdermally after 12 months

If the bleeding is prolonged or heavy then an ultrasound scan should be arranged.

Increasing the dose or progesterone or changing the type of progestogen may stop the bleeding (Mirena coil is the least likely to cause unscheduled bleeding) or reducing the dose of oestrogen or stopping HRT are alternative options.

If these changes do not result in a cessation of unscheduled bleeding after 6 months of starting HRT or 3 months of changing the dosage/preparation then it is recommended to either stop HRT and organise an ultrasound if bleeding does not cease after 4 weeks, or organise an ultrasound scan within 6 weeks.

References

[1] MacLennan AH, MacLennan A, Wenzel S, Chambers HM, Eckert K. Continuous low-dose oestrogen and progestogen hormone replacement therapy: a randomised trial. Med J Aust 1993;159: 102–6.

[2] de Medeiros SF, Yamamoto MMW, Barbosa JS. Abnormal bleeding during menopause hormone therapy: insights for clinical management. Clin Med Insights Womens Health 2013;6:13–24.

[3] Hahn RG. Compliance considerations with estrogen replacement: withdrawal bleeding and other factors. Am J Obstet Gynecol 1989;161:1854–8.

[4] Lou YY, Kannappar J, Sathiyathasan S. Unscheduled bleeding on HRT – do we always need to investigate for endometrial pathology? Int J Reprod Contracept Obstet Gynecol 2017;6:4174–8.

[5] Whitehead MI, Hillard TC, Crook D. The role and use of progestogens. Obstet Gynecol. 1990;75:559- 76.

[6] Management of unscheduled bleeding on hormone replacement therapy (HRT) British Menopause Society https://thebms.org.uk/wp-content/uploads/2024/04/01-BMS-GUIDELINE-Management-of-unscheduled-bleeding-HRT-APRIL2024-D.pdf