_ RCGP Learning

Written by Dr Toni Hazell 

Menopause is defined as a biological stage in a woman’s life when menstruation stops permanently, due to the loss of ovarian follicular activity. It is a retrospective diagnosis, made 12 months after the last period, which often follows several years of perimenopause in which periods can be irregular and menopausal symptoms may be felt. The average age of the menopause in the UK is 51. An early menopause is one that happens before 45. Premature ovarian insufficiency (POI) is defined as the transient or permanent loss of ovarian function below the age of 40¹. Care for women with POI should be holistic – as well as the risks to physical health, POI can be very distressing, particularly for those women who do not feel that they have completed their family.

A woman with POI may have an absolutely reduced number of ovarian follicles, or there may be remaining follicles which are not functioning properly. 90% of POI is idiopathic, but the following causes of a reduction or poor function of the follicles may be found in up to 10% of women²:

• Chromosomal disorders (e.g. Fragile X and Turner syndrome)
• Autoimmune disease (e.g. thyroiditis and Addison’s)
• Iatrogenic (e.g. due to the use of chemotherapy or pelvic radiotherapy or surgical after oophorectomy)
• Metabolic disorders (e.g. galactosaemia)
• Toxins such as cigarette smoke and some chemicals and pesticides can speed up follicle depletion
• Infection (e.g. mumps, TB and malaria – this is rare).

POI should be suspected in women who are under than 40 who have at least four months of amenorrhoea, with an estimated FSH level of more than 30 IU/L on two blood samples taken 4 – 6 weeks apart^1,2,3. If the diagnosis is in doubt, then a referral should be done⁴. Referral might be to a specialist menopause clinic, to endocrinology or to gynaecology, depending on your specific concerns and what pathways you have available locally. A full history should be taken, including:

• a review of menopausal symptoms
• other possible causes (including pregnancy)
• lifestyle factors (smoking, alcohol, exercise, nutrition)
• the need for contraception (women with POI still have a small risk of ovulation)
• smear status
• family history of POI, venous thromboembolism or breast cancer
• the woman’s thoughts about HRT use
• any co-morbidities which might be relevant when considering HRT use
• osteoporosis risk – consider a baseline assessment of bone mineral density, with a repeat 2-3 years after diagnosis³.

Those who have worked in primary care for decades will be aware of the changing demand for hormone replacement therapy (HRT) over the years, with a significant decline in the early 2000s⁵, associated with concerns about cardiovascular risk and breast cancer, often based on studies looking at different populations from those who are prescribed HRT in the UK. This has been reversed in the last few years, with a 35% increase in HRT items prescribed from 2020/21 to 2021/22⁶. It is vital that healthcare professionals understand the key difference between prescribing HRT for women who go through their menopause at a normal age, and those with POI, as the risk/benefit analysis is completely different. For women with POI, HRT is merely replacing the hormones that an average woman would have had naturally and reducing the excess risk of osteoporosis that comes with POI. For the vast majority there appears to be no excess risk of breast cancer arising from the use of HRT up to the age of 50³. Both NICE⁴ and the British Menopause Society³ (BMS) are clear that this cohort of women should be offered HRT unless there is a clear absolute or relative contraindication, the main one being a history of a hormone sensitive cancer such as breast cancer. All the data that we have suggests that transdermal oestrogen does not increase the risk of venous thromboembolism (VTE) in women who have their menopause at a normal age^3,4 – the BMS acknowledges the limited data in women with POI but says that the transdermal route should be considered in women with POI who are at an increased risk of VTE, for example due to obesity. Transdermal oestrogen, when used with micronised progesterone, is also ‘unlikely to significantly increase VTE risk above the individual’s intrinsic risk’⁷ for those who have a personal or family history of VTE.

The decision as to whether to refer a woman with POI to a specialist menopause clinic will depend on several factors. These may include the level of suspicion of an underlying cause, the confidence of the GP to manage POI, the woman’s desire for ongoing fertility, a need for specialist psychological input and any individual risk factors for HRT. For women with a history of a hormone sensitive cancer, a referral to discuss the risks and benefits of HRT would be sensible, and this discussion might usefully include her oncologist.

Women who go through their menopause at a normal age are advised to use contraception for one year after their last period (if that happens over the age of 50), or two years if their last period is under the age of 50. Women with POI have a higher risk of spontaneous ovulation and conception and have around a 5 – 10% change of spontaneous natural conception³. Contraception is therefore advised if they do not want to become pregnant and some will prefer to use combined hormonal contraception (CHC) instead of HRT – either are suitable options for oestrogen replacement (assuming no contraindications to combined hormonal contraception), although HRT may be more beneficial for bone health and cardiovascular risk³. They should continue to have smear tests at the normal frequency for their age. If a woman has no need for contraception (e.g. post sterilisation) and has no other licensed indications (e.g. menstrual symptoms) and is using CHC because she prefers it to HRT, then this will be unlicensed.

A diagnosis of POI can have physical, social, and psychological impacts on a woman and her family so holistic care is important. Signposting to a charity such as The Daisy Network⁸ and to reliable sources of information such as the Women’s Health Concern⁹, Rock My Menopause¹⁰, the RCOG menopause hub¹¹, and articles on the website Patient¹² may help her to feel more in control. GPs who wish to learn more about menopause might want to start with the RCGP course on the subject, consisting of a half-hour eLearning module, a short screencast and a podcast¹³. Access Menopause eLearning course via the following link https://elearning.rcgp.org.uk/course/info.php?id=663

Declaration of interests – Dr. Hazell does both paid and unpaid work for the PCWHF, who host Rock My Menopause, and also works for the website Patient.

References (all viewed 26.5.23)

1)     NICE CKS. Menopause. Last updated September 2022. https://cks.nice.org.uk/topics/menopause/

2)     Daisy network. What is POI. https://www.daisynetwork.org/about-poi/what-is-poi/

3)     British Menopause Society. Premature Ovarian Insufficiency. April 2020. https://thebms.org.uk/publications/consensus-statements/premature-ovarian-insufficiency/

4)     NICE. NG23. Menopause: diagnosis and management. Last updated December 2019. https://www.nice.org.uk/guidance/ng23

5)     Cagnacci A, Venier M. The Controversial History of Hormone Replacement Therapy. Medicina (Kaunas). 2019 Sep 18;55(9):602

6)     NHSBSA Statistics and Data Science. Hormone replacement therapy – England. October 2022. https://www.nhsbsa.nhs.uk/statistical-collections/hormone-replacement-therapy-england/hormone-replacement-therapy-england-april-2015-june-2022

7)     Hamoda H, Panay N, Pedder H et al. The British Menopause Society & Women's Health Concern 2020 recommendations on hormone replacement therapy in menopausal women. Post Reprod Health. 2020 Dec;26(4):181-209

8)     The Daisy Network. https://www.daisynetwork.org/

9)     Women’s Health Concern. https://www.womens-health-concern.org/

10)  Rock My Menopause. Premature ovarian insufficiency factsheet. https://rockmymenopause.com/portfolio-item/premature-ovarian-insufficiency

11)  RCOG. Menopause and later life. https://www.rcog.org.uk/for-the-public/menopause-and-later-life/

12)  Patient. What it’s like to go through early menopause. Last updated June 2019. https://patient.info/news-and-features/what-its-like-to-go-through-early-menopause

13)  RCGP eLearning. Menopause. September 2022.  https://elearning.rcgp.org.uk/course/view.php?id=663

14) Eunice Kennedy Shriver National Institute of Child Health and Human Development. What causes POI? https://www.nichd.nih.gov/health/topics/poi/conditioninfo/causes