What is the Best Management Strategy for a 20-year-old Woman With Premature Ovarian Failure?

Treatment

Hormone Replacement Therapy

Hormone replacement therapy (HRT) is recommended to treat the symptoms of POF and prevent adverse effects of oestrogen deficiency. Little research has been undertaken to determine the optimal hormone replacement regimen in POF. In the absence of evidence, it is appropriate to provide physiological replacement of the hormone deficiency. In practice, this means using oestradiol-based HRT. Transdermal therapy offers the advantage of bypassing first-pass metabolism and therefore the predominant circulating oestrogen is oestradiol, matching the normal premenopausal state. However, young women with POF may be reluctant to use a patch because it may be seen by others. Oestradiol gel is available, but most women prefer an oral HRT.

All women with a uterus must use a regimen containing progestogen to prevent endometrial hyperplasia. Cyclical HRT preparations that include 14 days of progestogen to induce monthly bleeds are more physiological than continuous combined HRT. The comparative long-term effects are unknown. However, some women do not wish to experience periods. A progestogen-containing intrauterine device can be considered.

The combined oral contraceptive pill (COCP) is another option for hormone replacement. It provides synthetic oestrogen with progestogen in a cyclical formulation. It may be preferred by young women as it is a medication they are familiar with, it does not carry HRT's association with menopause, and it is more 'peer-friendly'. The standard COCP is taken for 3 weeks of 4, and some young women are symptomatic in the week off, but 2–3 packets may be run together to give more continuous replacement. For a 20-year-old woman, there is no evidence that the COCP is inferior or superior to HRT as a form of hormone replacement. Compliance with medication is very important in this group of women who will need to take long-term treatment, and so if the COCP is her preference, then this should be used.

There are very few absolute contra-indications to HRT in young women with POF. For the vast majority, the benefits of oestrogen replacement will outweigh any risks. Transdermal oestradiol should be advised where appropriate, for example in women with migraine or with risk factors for venous thromboembolism. Appropriate multidisciplinary input should be sought for complex cases.

The use of testosterone replacement in POF is controversial and has only been studied in the context of surgical menopause. In the absence of evidence, it seems reasonable to give a trial of testosterone, in the form of patch or gel, if low libido or lack of energy persists despite adequate oestrogen replacement.

Other Treatments

Hormone replacement therapy is the most appropriate treatment for symptoms and bone loss in POF. Medications such as selective serotonin reuptake inhibitors, venlafaxine and clonidine, which are sometimes used to treat hot flushes in older women, have poor efficacy^[28] and do not relieve other symptoms or provide bone protection. The use of bisphosphonates in a young population, including very long-term side effects, has not been assessed. They should be discontinued in any patient considering pregnancy.

Complementary Therapy

Women often ask about and are keen to try complementary therapies. It is likely that these are widely used, but there is no convincing evidence for their efficacy.^[28] Even if complementary therapies help with hypo-oestrogenic symptoms, they will not offer protection against osteoporosis or cardiovascular disease.

Lifestyle Factors

Calcium and vitamin D are important in bone metabolism. Most of the recommended daily intake of 1200 mg calcium should be obtained from the diet, with supplements provided if necessary.^[29] Vitamin D deficiency is common, particularly in women who cover their skin for religious or cultural reasons, do not go outside or always use sunscreen. Vitamin D and calcium supplements have been found to reduce the risk of hip fracture in elderly people living in care homes,^[30] but there are no data in young people. Most HRT trials in older women showing that HRT has a beneficial effect on bone density have provided supplements, and therefore women may choose to take them. Gastrointestinal symptoms and renal calculi are more common in those taking supplements.^[30]

This is a good opportunity to discuss other lifestyle factors that can help prevent bone loss and reduce cardiovascular risk. These include weight-bearing exercise, limiting caffeine and alcohol intake and smoking cessation.

Clin Endocrinol. 2012;77(2):182-186. © 2012 Blackwell Publishing