A 29-year-old woman presents with irregular periods and hot flushes for the past four months. She has two normally developed boys and is using a copper-bearing intrauterine device for contraception. Her mother became menopausal at the age of 35 years.
What tests should you do?
What are the long-term health implications?
What treatment should you recommend?
What are the fertility/contraception issues?
Premature ovarian failure (POF) is common.1,2 It is estimated to affect 1% of women younger than 40 years and 0.1% of those under 30 years. It can present as primary or secondary amenorrhoea. In the great majority of cases, no cause can be found. Women with POF frequently have autoimmune disorders, particularly hypothyroidism (25%), Addison's disease (3%) and diabetes mellitus (2.5%). Other coexisting conditions may include Crohn's disease, vitiligo, pernicious anaemia, systemic lupus erythematosus or rheumatoid arthritis. While follicle-stimulating hormone (FSH) receptor gene polymorphisms, inhibin B mutations and enzyme deficiencies can cause POF, presentation is at a much younger age. A critical region on the X-chromosome (POF1), ranging from Xq13 to Xq26, which relates to normal ovarian function has been identified, as has a second gene of paternal origin (POF2), which is located at Xq13.3–q21.1. Idiopathic POF can be familial or sporadic, and the familial pattern of inheritance is compatible with X-linked inheritance with incomplete penetrance or an autosomal dominant mode of inheritance. Familial POF has been linked with fragile X permutations. Although women with POF are generally considered to be infertile, spontaneous ovarian activity may occur with the resulting implications of fertility and pregnancy.
What tests should you do?
A diagnosis of POF must be made with two FSH measurements preferably during menstruation or two weeks apart if periods are very infrequent.2 Other endocrine disease (such as thyroid dysfunction) that can also cause hot flushes and menstrual irregularity should be excluded (Table 12.1). Coexisting disease must be detected, particularly hypothyroidism, Addison's disease and diabetes mellitus. The prevalence of antibodies directed against the ovary has been the subject of significant research. Circulating anti-ovarian antibodies have been found in 10%–69% of women with POF but also in a significant number of controls. Chromosome analysis is unlikely to reveal any abnormality since her children are normal. The diagnostic usefulness of ovarian biopsy outside the context of a research setting has yet to be proved.3 No single test such as FSH, luteinizing hormone, oestradiol, inhibin B and anti-Mullerian hormone, total antral follicle count and ovarian volume are reliable in predicting ovarian reserve and fertility. A combination of markers ultimately may be more helpful. In the absence of risk factors for osteoporosis, bone mineral density is unlikely to be compromised since the patient is still menstruating and this measurement can be deferred.
Table 12.1Investigation of premature menopause