What is the diagnosis and treatment for Primary Ovarian Insufficiency (POI)?

From the Guidelines

Primary ovarian insufficiency (POI) should be managed with hormone replacement therapy (HRT) to reduce the risk of osteoporosis, cardiovascular diseases, and urogenital atrophy, and to improve the quality of life of women with POI, as recommended by the most recent study in 2021 1.

Key Considerations

• POI is defined as the combination of oligo/amenorrhea and raised follicle-stimulating hormone (FSH) levels within the menopausal range, recorded at least twice four weeks apart, in patients younger than 40 years 1.
• HRT is indicated to induce the progression of secondary sexual characteristics in pre/peripubertal patients who experienced early-onset POI with pubertal delay or pubertal arrest as a consequence of the detrimental effect of antineoplastic agents on ovarian function 1.
• A multidisciplinary team including gynecologists, pediatricians, endocrinologists, dietitians, and psychologists should manage children, adolescents, and young women with POI 1.

Treatment Recommendations

• The goal of HRT in adult patients with POI is to restore normal serum estrogen concentrations according to age, with a common regimen including 17-beta estradiol (1-2 mg daily) combined with cyclic progesterone (200 mg for 12 days each month) for women with an intact uterus 1.
• The choice of estrogen therapy should be combined with appropriately dosed progestogen therapy in non-hysterectomized women 1.
• A systematic approach to hormonal therapy in post-pubertal adolescents and young women with iatrogenic premature ovarian insufficiency should be based on a pragmatic treatment protocol, considering contraception requirements and withdrawal bleeding acceptance 1.

Monitoring and Prevention

• Regular monitoring with a healthcare provider is essential, including bone density scans every 1-2 years and cardiovascular risk assessment 1.
• Women with POI should also ensure adequate calcium intake (1200-1500 mg daily) and vitamin D (800-1000 IU daily), along with regular weight-bearing exercise 1.
• While spontaneous pregnancy is possible in 5-10% of women with POI, those desiring pregnancy may need to consider egg donation 1.

From the FDA Drug Label

Treatment of hypoestrogenism due to hypogonadism, castration or primary ovarian failure. For treatment of female hypoestrogenism due to hypogonadism, castration, or primary ovarian failure. Treatment is usually initiated with a dose of 1 to 2 mg daily of estradiol, adjusted as necessary to control presenting symptoms; the minimal effective dose for maintenance therapy should be determined by titration.

Estradiol is indicated for the treatment of primary ovarian insufficiency (also referred to as primary ovarian failure). The recommended initial dosage is 1 to 2 mg daily, adjusted as necessary to control symptoms, with the goal of determining the minimal effective dose for maintenance therapy through titration 2 2.

From the Research

Definition and Symptoms of Primary Ovarian Insufficiency

• Primary ovarian insufficiency describes a spectrum of declining ovarian function and reduced fecundity due to a premature decrease in initial follicle number, an increase in follicle destruction, or poor follicular response to gonadotropins 3.
• Symptoms of primary ovarian insufficiency include vasomotor symptoms, urogenital atrophy, osteoporosis and fracture, cardiovascular disease, and increased all-cause mortality 3, 4.

Hormone Replacement Therapy

• Systemic hormone therapy (HT) is an effective approach to treat the symptoms of hypoestrogenism and mitigate long-term health risks in women with primary ovarian insufficiency, if there are no contraindications to treatment 3.
• Hormone replacement therapy (HRT) is strongly recommended for women with primary ovarian insufficiency, mainly for vasomotor and genito-urinary symptom relief, as well as for bone protection and primary prevention of cardiovascular disease 5.
• The treatment should be implemented at recognition of the primary ovarian insufficiency and continued to at least the age of natural menopause, around 50-51 years 3, 4, 6.

Types and Regimens of Hormone Replacement Therapy

• Transdermal estradiol and oral or vaginal progesterone administration provide the most physiological sex steroid replacement therapy 6.
• Combined hormonal contraceptives prevent ovulation and pregnancy more reliably than HT, and may be considered for women with primary ovarian insufficiency who deem pregnancy prevention a priority 3.
• Patient preference for route and method of administration of each component of HRT must be considered when prescribing, as well as contraceptive needs 5.

Management and Long-Term Consequences

• Women with primary ovarian insufficiency should be managed by a multidisciplinary team, such as a gynaecologist, endocrinologist, dietitian, and psychologist 6.
• Properly selected therapy improves the quality of women's lives and reduces the risk of mortality, including the risk of cardiovascular diseases, osteoporosis, and genitourinary syndrome 6.
• Further research is needed to optimize the benefits of hormone replacement therapy in women with primary ovarian insufficiency, including studies on patient-important outcomes such as fractures, stroke, and cardiovascular mortality 7.