Obstetrics and Gynecology/Premature Ovarian Failure

Premature Ovarian Failure is the pathological cessation of ovarian function before the age of 40.

Epidemiology

Incidence

• 1 in 10,000 women by age 20
• 1 in 1,000 women by age 30
• 1 in 100 women by age 40

Risk Factors

• Genetic Inheritance
• High Level of Education
• Low Parity
• Family history and/or past medical history of galactosemia and/or neurofibromatosis

Resulting Problems

• Infertility
• Osteoporosis

Associated Conditions

• Hashimoto's Thyroiditis
• Heart Disease
• Addison's Disease
• Hypoparathyroidism
• Diabetes Mellitus

Etiology and Pathogenesis

In a lot of cases the etiology is unknown. Known causes of premature ovarian failure include:

• Inhibin α-subunit gene has been suggested to play a role due to its role in the negative feedback control of Follicular Stimulating Hormone (FSH)
• An autoimmune response (Schmidt's syndrome) has also been implicated, explaining the associated conditions
• Genetic disorders such as Turner's syndrome and Fragile X syndrome
• Resistance of gonadotrophin by ovarian gonadotrophin receptors
• RNA Paramyxovirus infection
• Galactosaemia
• Neurofibromatosis
• Chemotherapy and radiotherapy
• Bilateral ovarian surgery

The pathogenesis of premature ovarian failure is very easy to understand. It comes in two forms, no matter what the etiology:

1. The ovaries have no remaining ova
2. No response to FSH due to FSH antibodies

Clinical Features

History

Symptoms may include:

• Secondary Amenorrhoea or oligomenorrhoea
• Palpitations
• Heat intolerance
• Flushes
• Night sweats
• Irritability
• Anxiety
• Depression
• Sleep disturbance
• Decreased libido
• Hair coarseness
• Vaginal dryness
• Fatigue

Examination

There is nothing of note in the Gynecological examination so a general examination should be performed and should be particularly geared towards discrepancies in other systems

Investigations and Diagnosis

Diagnosis is confirmed with an FSH level of a value greater than 20IU/L and an E₂ level of a value less than 50pmol/L. Other tests that can be performed include:

• Karyotyping in those patients under 30
• Thyroid function - TSH and T₄
• Parathyroid function - Ca and phosphate
• Adrenal function - Cortisol

Prognosis and Management

Because ovarian failure can be intermittent in nature, infertility is not always complete and permanent. However, the likelihood of conception without oocyte donation is very slim. Management must depend on whether the woman wants to conceive a child. Hormone replacement therapy is the desired treatment for those patients who wish to start or continue a family. In those patients who have completed a family or have no desire for children, the combined contraceptive pill is the most appropriate method of treatment.

References

• Coulam C B et al. Incidence of Premature Ovarian Failure. Obstet. Gynecol. 1986;67(604-606)
• Testa G et al. Case-Control Study on Risk Factors for Premature Ovarian Failure. Gynecologic and Obstetric Investigation. 2001;51 (40-43)
• Beck-Peccoz P, Persani L. Premature Ovarian Failure. Orphanet Journal of Rare Diseases 2006;10.1186/1750-1172-1-9.
• www.gpnotebook.co.uk