Greater Glasgow and Clyde Medicines

Patient Safety: Unopposed Oestrogen Prescribing

Key Points:

  • Women with an intact uterus prescribed hormone replacement therapy (HRT), require both oestrogen and progestogen. The progestogen provides endometrial protection against the risk of endometrial hyperplasia and endometrial cancer.
  • It is the responsibility of the prescriber to ensure robust systems are in place to prevent women with an intact uterus receiving unopposed oestrogen.
  • When Mirena® Intrauterine system (IUS) is being used as the progestogenic component of HRT then the date of insertion must be under 5 years. Additional progestogen for endometrial protection must be prescribed if past this date.
  • If a woman prescribed unopposed oestrogen is identified, HRT must be amended accordingly to a combined preparation and a referral made to gynaecology or sexual health services for endometrial assessment.


HRT treatment is available in different forms and treatment is individualised according to the patient’s symptoms, medical history and preference. The intention is always to use the lowest effective dose that achieves symptom control. HRT can be given orally or transdermally (patches, spray or gel).

Combined oestrogen-progestogen preparations are available for women with an intact uterus. Oestrogen alleviates symptoms whilst progestogen provides endometrial protection.

Estradiol-only preparations are available only for women without a uterus


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HRT regimens for women with an intact uterus

Cyclical preparations (also called sequential HRT)

For women with menstrual cycles or those who are within 1 year of their last cycle (perimenopausal).

NHSGGC formulary preparations

  • Provides daily oestrogen alone for the first part of each month, followed by oestrogen and progestogen for the remaining days.

  • Preparations are available as combined tablets or in the form of a combined patch.

  • At times, it may be necessary to separate the oestrogen and progestogen. An example may be an oestrogen patch, gel or spray, with an oral progestogen. This is a more complicated regimen, but may be required for some women. Progestogen can be given as medroxyprogesterone acetate 10mg (Provera®) daily.

Continuous combined preparations

Due to the risk of irregular bleeding, these preparations are reserved for women where 12 months have elapsed since the last menses or in women commencing HRT over the age of 54 years.

NHSGGC formulary preparations

  • Provides oestrogen and progestogen throughout the cycle.

  • Preparations are available as combined tablets or in the form of a combined patch.

  • If prescribed an oestrogen only preparation, then progestogen can be given as medroxyprogesterone acetate 5mg (Provera®) daily.

Levonorgestrel Intrauterine system (Mirena®)

Licensed for endometrial protection as part of the HRT regime. Mirena® is particularly helpful:

  • When there are heavy bleeds with sequential HRT

  • When contraception is still required along with HRT

  • When there are systemic side effects from the progestogen part of HRT.

  • Releases progestogen directly into the womb and provides excellent protection of the womb lining in both perimenopause and postmenopause.

  • It allows for more flexibility as any estradiol dose or preparation which is suitable for the woman can be prescribed.

  • Mirena® currently has a four year licence for this indication; however The Faculty of Sexual and Reproductive Healthcare guidance now states that 5 year use is acceptable. This guidance can also be accessed at GP notebook or NICE CKS.


Other Special circumstances:

  • Subtotal hysterectomy: There is always the possibility of residual endometrium. In these cases, a combined preparation should be used. Discuss with a consultant gynaecologist or refer to a specialist menopause clinic if unopposed oestrogen is considered.
  • Previous hysterectomy for endometriosis: These cases should be considered individually. Unopposed oestrogen or continuous combined preparations can be prescribed.


Published: 17/05/2022. Medicines Update blogs are correct at the time of publishing

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