Premature ovarian insufficiency Flashcards
What are the criteria necessary for a diagnosis of primary ovarian insufficiency?
POI= Menopause before the age of 40 and is diagnosed by meeting the following criteria:
- Menstrual disturbance: oligomenorrhoea or amenorrhoea for at least 4 months
- Raised gonodatrophins: FSH> 25, LH > 15 on 2 occasions 1 month apart
- Oestrogen deficiency:
o Symptoms: vasomotor- flushes, night sweats, fatigue, mood swings, vaginal dryness
o Biochemically: low estradiol levels
What are the causes of POI?
- Chromosomal and genetic:
- X-chromsome anolomalies eg turners
- Fragile X syndrome (FMR-1 gene)
- autosomal gene defects: galactosaemia (i.e. a genetic condition that affects the body’s ability to process galactose)
- Autoimmune disorders
- coeliac disease
- Addisons
- APS
- Thyroid disease
- T1DM
- Infections
- potentially but not proven Mumps, HIV,herpes zoster,CMV, TB,malaria,varicella, shingels
- Iatrogenic
- Ovarian surgery
- radiotherapy (after cancer treatment 35%)
- Chemotherapy
- Enviromental
- smoking, etoh, nutrition, obesity
- Idiopathic (up to 50%)
What is the prevalence of POI?
The prevalence of POI is approximately 1%. Population characteristics such as ethnicity may affect the prevalence.
In view of the long-term health consequences of POI, efforts should be made to reduce the incidence of POI. Modifiable factors may include:
gynaecological surgical practice
lifestyle – smoking
modified treatment regimens for malignant and chronic diseases.
What are the implications for relatives of women with POI?
Relatives of women with the fragile-X premutation should be offered genetic counselling and testing.
Relatives of women with non-iatrogenic premature ovarian insufficiency who are concerned about their risk for developing POI should be informed that:
- currently there is no proven predictive test to identify women that will develop POI, unless a mutation known to be related to POI was detected
- there are no established POI preventing measures
- fertility preservation appears as a promising option, although studies are lacking, and
- their potential risk of earlier menopause should be taken into account when planning a family.
What are the fertility options?
- Small chance of spontaneous pregnancy ( up to 5%), should use contraception if wishes to avoid pregnancy
- Inform women with POI that there are no interventions that have been reliably shown to increase ovarian activity and natural conception rates.
- Oocyte donation is an established option for fertility in women with POI.
- Inform women considering oocyte donation from sisters that this carries a higher risk of cycle cancellation.
- In women with established POI, the opportunity for fertility preservation is missed.
What are the obstetric risks associated with POI?
What are the obstetric risks associated with POI?
- Women should be reassured that spontaneous pregnancies after idiopathic POI or most forms of chemotherapy do not show any higher obstetric or neonatal risk than in the general population.
- Oocyte donation pregnancies are high risk and should be managed in an appropriate obstetric unit. Women and their partners should be encouraged to disclose the origin of their pregnancy with their obstetric team.
- Antenatal aneuploidy screening should be based on the age of the oocyte donor.
- Pregnancies in women who have received radiation to the uterus are at high risk of obstetric complications and should be managed in an appropriate obstetric unit.
- Pregnancies in women with Turner Syndrome are at very high risk of obstetric and non-obstetric complications and should be managed in an appropriate obstetric unit with cardiologist involvement.
- A cardiologist should be involved in care of pregnant women who have received anthracyclines and/or cardiac irradiation.
How should fitness for pregnancy be assessed in women with POI?
Women presenting for oocyte donation who are suspected of having POI should
be fully investigated prior to oocyte donation, including thyroid and adrenal function as well as karyotype.
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- Women previously exposed to anthracyclines, high dose cyclophosphamide or mediastinal irradiation should have an echocardiogram prior to pregnancy, and referral to a cardiologist if indicated.
- Women with Turner Syndrome should be assessed by a cardiologist with a specialist interest in adult congenital heart disease and should have a general medical and endocrine examination.
- Women with POI should have their blood pressure, renal function, and thyroid function assessed prior to pregnancy.
- Pregnancy in some women can be of such high risk that clinicians may consider oocyte donation to be life threatening and therefore inappropriate.
What are the consequences of POI for bone health?
- POI is associated with reduced bone mineral density (BMD).
- Reduced BMD is very likely to indicate that POI is associated with an increased risk of fracture later in life, although this has not been adequately demonstrated
What are the treatment options for bone protection and improvement?
- Women should maintain a healthy lifestyle, involving weight-bearing exercise, avoidance of smoking, and maintenance of normal body weight to optimize bone health.
- A balanced diet will contain the recommended intake of calcium and vitamin D. Dietary supplementation may be required in women with inadequate vitamin D status and/or calcium intake, and may be of value in women with low BMD.
- Estrogen replacement is recommended to maintain bone health and prevent osteoporosis; it is plausible that it will reduce the risk of fracture.
- The combined oral contraceptive pill may be appropriate for some women but effects on BMD are less favourable.
- Other pharmacological treatments, including bisphosphonates, should only be considered with advice from an osteoporosis specialist. Particular caution applies to women desiring pregnancy.
How should bone health be monitored in women with POI?
- It is important to consider bone health at diagnosis in POI, and during ongoing care.
- Measurement of BMD at initial diagnosis of POI should be considered for all women, but especially when there are additional risk factors.
- If BMD is normal and adequate systemic estrogen replacement is commenced, the value of repeated DEXA scan is low.
- If a diagnosis of osteoporosis is made and estrogen replacement or other therapy initiated, BMD measurement should be repeated within 5 years. A decrease in BMD should prompt review of estrogen replacement therapy and of other potential factors. Review by a specialist in osteoporosis may be appropriate.
What are the consequences of POI for the cardiovascular system?
- Women with POI are at increased risk of cardiovascular disease and should be advised of risk factors that they can modify through behavioural change (e.g. stopping smoking, taking regular weight-bearing exercise, healthy weight).
- All women diagnosed with Turner Syndrome should be evaluated by a cardiologist with expertise in congenital heart disease.
Despite lack of longitudinal outcome data, hormone replacement therapy with early initiation is strongly recommended in women with POI to control future risk of cardiovascular disease; it should be continued at least until the average age of natural menopause.
- Cardiovascular risk should be assessed in women diagnosed with POI. At least blood pressure, weight and smoking status should be monitored annually with other risk factors being assessed if indicated.
- In women with Turner Syndrome, cardiovascular risk factors should be assessed at diagnosis and annually monitored (at least blood pressure, smoking, weight, lipid profile, fasting plasma glucose, HbA1c).
What treatments are available for genito-urinary symptoms in POI?
- Local estrogens are effective in treatment of genito-urinary symptoms.
- Clinicians should be aware that despite seemingly adequate systemic hormone replacement therapy (HRT), women with POI may experience genito-urinary symptoms. Local estrogens may be given in addition to systemic HRT.
- Lubricants are useful for treatment of vaginal discomfort and dyspareunia for women not using HRT.
What are the management options for the effect of POI on neurological function (cognition)?
- Estrogen replacement to reduce the possible risk of cognitive impairment should be considered in women with POI at least until the average age of natural menopause.
- Women with POI should be advised to take lifestyle measures (e.g. exercise, cessation of smoking, maintaining a healthy weight) to reduce possible risks for cognitive impairment.
