From the Guidelines
Premature ovarian failure (POF), now often called primary ovarian insufficiency, should be diagnosed in women under 40 years who present with amenorrhea, elevated FSH levels (>25 IU/L on two occasions at least 4 weeks apart), and estrogen deficiency, and managed primarily with hormone replacement therapy (HRT) until the average age of natural menopause (around 51 years) to prevent complications of estrogen deficiency, as recommended by the European Society of Human Reproduction and Embryology (ESHRE) guideline 1.
Diagnosis
The diagnosis of POF involves:
- Amenorrhea
- Elevated FSH levels (>25 IU/L on two occasions at least 4 weeks apart)
- Estrogen deficiency
Management
The management of POF primarily involves HRT, which includes:
- 17β-estradiol 1-2mg daily with cyclic progesterone (medroxyprogesterone acetate 5-10mg for 12-14 days monthly or micronized progesterone 200mg daily for 12 days monthly) for women with an intact uterus, as suggested by recent practical recommendations for hormonal replacement therapy in adolescents and young women with chemo- or radio-induced premature ovarian insufficiency 1
- Transdermal estradiol patches (50-100μg) as an alternative with potentially lower thrombotic risk
- Calcium supplementation (1200mg daily) and vitamin D (800-1000 IU daily) for bone health, along with regular weight-bearing exercise and bone density monitoring
- Psychological support, as POF can cause significant distress, particularly regarding fertility loss
Follow-up
Regular follow-up should include:
- Cardiovascular risk assessment, as estrogen deficiency increases risk of heart disease
- Screening for associated autoimmune conditions like thyroid disease and adrenal insufficiency, particularly in cases with autoimmune etiology
- Consideration of sex steroid replacement therapy for pre-, peri- and post-pubertal survivors diagnosed with premature ovarian insufficiency, as recommended by the international late effects of childhood cancer guideline harmonization group 1
From the Research
Diagnosis of Premature Ovarian Failure
- Premature ovarian failure (POF), also known as primary ovarian insufficiency, is diagnosed when primary or secondary amenorrhea and hypoestrogenism with high levels of gonadotropins occur in women before the age of 40 2.
- The diagnosis of POF is based on the presence of genetic, autoimmune, and environmental factors that lead to a decrease in numbers of primordial follicles, accelerated atresia, and impaired follicular function 2.
Management of Premature Ovarian Failure
- The diagnosis of POF is an indication for hormonal replacement therapy (HRT), which should be continued until the mean age of menopause in a given population 2.
- HRT reduces the intensity of vasomotor symptoms and has a beneficial effect on the central nervous, skeletal, cardiovascular, and urinary-reproductive systems 2.
- Properly selected therapy improves the quality of women's lives and reduces the risk of mortality 3.
- Transdermal oestradiol and oral or vaginal progesterone administration provide the most physiological sex steroid replacement therapy 3.
- Patients' views and individual preference according to the route, dose, and regimen of hormonal treatment have to be taken into consideration in order to achieve high compliance rates 3.
Health Implications and Treatment
- Premature ovarian insufficiency (POI) correlates with increased risk of cardiovascular diseases, osteoporosis, genitourinary syndrome, and other symptoms of prolonged oestrogen deprivation 3.
- Women with POI should be managed by a multidisciplinary team, such as a gynaecologist, endocrinologist, dietitian, and psychologist 3.
- Estrogen therapy is the mainstay of management, and postmenopausal estrogen therapy studies should not be used to determine the risks of treatment in these young women 4.
- The effect of micronized progesterone and medroxyprogesterone acetate in combination with transdermal estradiol on hemostatic biomarkers in postmenopausal women diagnosed with POI and early menopause has been studied, and the results suggest a neutral effect of both progestogens on the global coagulation assay 5.
Treatment Options
- There is a wide spectrum of available oestrogen and progestogen formulations restoring proper levels of serum sex steroid hormones 3.
- The treatment should be implemented at recognition of the POI and continued to at least the age of natural menopause 3.
- Micronized progesterone and medroxyprogesterone acetate are two progestogen options that can be used in combination with transdermal estradiol 6, 5.