Premature Ovarian Insufficiency (Menopause <40y)

Overview

Premature Ovarian Insufficiency (POI) is defined as ovarian failure under the age of 40years. Prevalence is estimated to be 1%. Women in this group are at increased risk of cardiovascular disease, osteoporosis and cognitive impairment. Untreated, women will have a reduced life expectancy.  

HRT until the age of 51 (average age of menopause) is cardioprotective, improves bone density, and does not increase breast cancer risk above the baseline risk of a woman of the same age with ovarian function. Therefore, HRT should be discussed with and offered to all women with POI (regardless of symptoms), as well as appropriate lifestyle interventions.  

Diagnosis

1. Under age 40 at time of diagnosis  
2. Oligo/amenorrhoea for >4months duration 
3. Elevated (>25 iu/L) FSH on at least two occasions, measured at least 4-6weeks apart (do not measure FSH whilst a patient is using combined hormonal contraception, estradiol or injectable contraceptives)  

Consider repeating FSH level if one normal and one abnormal result in the context of on-going symptoms or concerns, or risk factors present.   

Management

All women with a new diagnosis of POI should be managed by an appropriate specialist. This may be a specialist in Primary Care, Complex Menopause clinic, Reproductive Medicine clinic, Fertility clinic or Paediatric Adolescent Gynaecology, dependent on patient factors.  

Hormone replacement in the form of hormone replacement therapy (HRT) or the combined oral contraceptive pill (COC) should be recommended for all women (unless contra-indicated) up until the age of 51. This should be started at the time of referral.  

• Reduces the long-term risk of cardiovascular disease and osteoporosis, and has a beneficial effect on cognition if started within 5-10 years of symptoms onset. 
• Provides symptom control   
• HRT does not increase the risk of breast cancer in this group up until the natural age of menopause compared to the general population.
• Follow the local HRT guidelines for advice on prescriptions.
• The aim of treatment with HRT is to achieve symptom relief. Women with POI may require higher doses of oestrogens than older women to achieve this. 
• HRT should be offered to all women, including those who are asymptomatic. These women should be prescribed standard doses.  
• The combined oral contraceptive (COC) pill can be used as an alternative to HRT, however HRT may be more beneficial in improving bone health and cardiovascular markers. Consider risk factors for taking the COC, and take into account patient preference, plus that COC can be used as a contraceptive (which HRT alone cannot). 
• Consider tricycling COC to reduce frequency of pill free interval (tricycling is an off-licence use which is supported by FSRH).  
• If symptomatic, topical oestrogen can be used to treat genitourinary symptoms in addition to systemic HRT. 

There is on-going national research to determine whether HRT or COC is a better management strategy for POI (Home - Poise) 

Qlaira ® (estradiol valerate, dienogest) (TLS Amber Specialist Recommended) is an option for patients with premature ovarian insufficiency requiring contraception and HRT cover where standard oral contraceptives are not suitable and patients have completed puberty. 

Lifestyle advice  

• Balanced diet, adequate calcium and vitamin D intake (consider replacement), weight bearing exercise, smoking cessation and avoidance of excess alcohol.  

Bone mineral density

• It is important to consider bone heath at diagnosis 

• FRAX scoring is not validated in those <40, however the risk factors remain relevant: 
  • Previous fractures
  • Parental hip fracture
  • Current smoker
  • Long term steroid use
  • Excess alcohol intake (>3units/day)
  • Rheumatoid arthritis  
  • Known osteoporosis
• QFracture is validated for use in women >33 (QFracture). Those with 10-year fracture risk > 10% may require a DXA scan. 
• Consider requesting a DXA for people with POI, PLUS an additional risk factor for osteoporosis (refer to FRAX for risk factors - frax.shef.ac.uk/FRAX/tool.aspx?country=1) 

• DXA reports will give a plan for follow up and repeat imaging if required.  

• If risk factors change or develop, a DXA should be requested as indicated. 

• If a person with POI is not using HRT (e.g. declined) then a DXA scan may be indicated to assess bone health.  

• Women with osteoporosis should be managed accordingly.  (Osteoporosis (Remedy BNSSG ICB))  

Follow up

As with all women established on HRT, those with POI should have an annual review to include – effectiveness of treatment, side effects, bleeding pattern, type and dose of hormone replacement, risk factors for bone health, and to assess ongoing risk vs benefit. Routine BP and BMI should be documented annually.  

Contraception and Fertility

Women with POI can have intermittent ovarian activity and have a small chance of spontaneous pregnancy, estimated to be 5-10%. For women wishing to pursue fertility outcomes, it is beneficial for them to have a regular bleed and therefore they should be advised to use sequential HRT or COC.  

Contraception should be discussed and offered as appropriate. HRT is not contraceptive. The COC can be used as an alternative to HRT and offers both hormone replacement and contraception. 

Women wishing to discuss their fertility options can be referred to the Reproductive Medicine clinic for advice, or advice can be sought via the Advice and Guidance service.  Those actively trying to conceive should be referred in line with local policy ( Infertility Assessment and Treatment Policy.docx).  As per the policy women with proven POI would be eligible for immediate referral for fertility assessment and treatment once fertility is desired (and do not have to have been trying for 2 years), providing they meet all other criteria.  As success with IVF with a woman’s own eggs in the context of POI is extremely low, those with a POI diagnosis would be eligible for IVF with egg donation but not for treatment with their own eggs.   

Referral

Referrals should be made via eRS to Gynaecology at NBT or the Menopause Triage service at UHBW.

Please do start hormone replacement therapy in the meantime.  

At time of referral please arrange the following investigations, if not already done, and manage as appropriate 

Resources

Patient Information  

Charity for Women with POI | The Daisy Network 

BRITSPAG HRT in Young Women - HRT-BritSPAG-Information-Leaflet-2019.pdf

ESHRE Patient information leaflets – 2 leaflets available Iatrogenic and Non-iatrogenic Recommended patient information (eshre.eu) 

Food for healthy bones - NHS (www.nhs.uk) 

Exercise - NHS (www.nhs.uk 

19-WHC-FACTSHEET-Osteoporosis-Bone-NOV2022-B.pdf (womens-health-concern.org) 

References

BMS Premature Ovarian Insufficiency Consensus Statement - Premature ovarian insufficiency - British Menopause Society (thebms.org.uk) 

ESHRE Guidelines – Management of Premature Ovarian Insufficiency Guideline on the management of premature ovarian insufficiency (eshre.eu) 

 FRAX calculator - frax.shef.ac.uk/FRAX/tool.aspx?country=1 

QFracture  

PCWHF_A-guide-to-managing-POI-in-primary-care_v2.pdf 

Efforts are made to ensure the accuracy and agreement of these guidelines, including any content uploaded, referred to or linked to from the system. However, BNSSG ICB cannot guarantee this. This guidance does not override the individual responsibility of healthcare professionals to make decisions appropriate to the circumstances of the individual patient, in consultation with the patient and/or guardian or carer, in accordance with the mental capacity act, and informed by the summary of product characteristics of any drugs they are considering. Practitioners are required to perform their duties in accordance with the law and their regulators and nothing in this guidance should be interpreted in a way that would be inconsistent with compliance with those duties.

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