Gonadal toxicity is the commonest long-term adverse effect of cancer therapy (see Chapter 1).1,2 In women and girls, complete loss of ovarian function causes permanent amenorrhoea and infertility. This was previously termed ‘ovarian failure’ or ‘premature menopause’ but the term ‘premature ovarian insufficiency’ is now preferred, as loss of function is often incomplete (analogous to thyroid insufficiency) and this terminology also avoids the stigma associated with ‘failure’ and ‘menopause’ in a young woman.3,4
Premature ovarian insufficiency (POI) is a condition defined by loss of ovarian function before the age of 40 and diagnosed by persistent menstrual disturbance and raised gonadotrophins.3 Menstruation is either absent or very infrequent. Follicle-stimulating hormone (FSH) is raised (above 25 iu/l). Luteinising hormone (LH) is also raised but less markedly than FSH. Serum oestradiol is low, usually unrecordable.
As POI is often a fluctuating condition, especially at onset, diagnosis requires menstrual upset to continue for at least 6 months, with two blood samples at least 6 weeks apart for confirmation. Many cancer survivors experience this phase, with intermittent symptoms and amenorrhoea followed by return of menstruation for a few months. Meanwhile FSH measurement fluctuates widely. Progression is often gradual, over several years, to complete loss of ovarian function.
Anti-müllerian hormone (AMH) measurement is not a diagnostic test of POI, and AMH is often extremely low for several years before clinical symptoms and signs develop. Pelvic ultrasound may be indicated, for example to exclude a physical cause of irregular or heavy bleeding, but is confirmatory rather than diagnostic.
Many young women have classic vasomotor symptoms of hot flushes and night sweats, and also vaginal dryness, loss of sexual interest, joint and muscle aches, loss of energy and low mood, and cognitive problems such as memory lapses and lack of focus. These symptoms can interfere with daily activities, may affect intimate relationships, and can impair effectiveness at work. The loss of confidence associated with survivorship for many patients is exacerbated by the perceived loss of womanhood and infertility. Infertility is often rated by cancer survivors as the most distressing outcome of treatment.5,6
Lack of oestrogen has serious long-term health consequences. Loss of bone mineral density leads to the early onset of osteoporosis, risking fragility fractures and the associated morbidity. There is also earlier onset of cardiac disease. In the general population, epidemiological studies show a slightly shortened life expectancy after POI, largely due to cardiovascular disease.7 Long-term follow-up of women who have had a surgical menopause also suggests an increased risk of neurological problems, Parkinsonism and dementia.8 Unfortunately there are no large studies of any long-term sequelae of POI in cancer survivors.
Oestrogen replacement therapy is the cornerstone ...