[5] Physical and emotional symptoms are similar to those seen during menopause and can include hot flashes, night sweats, dry skin, vaginal dryness, irregular or absent menstruation, anxiety, depression, mental fog, irritability, nervousness, decreased libido, and increased autoimmune disruption.
[1][11] Although 5 to 10% of women with POI may ovulate sporadically and become pregnant without treatment,[12] others may use assisted reproductive technology including in vitro fertilization and egg donation[13] or decide to adopt or remain childless.
[6] It can be associated with genetic causes, autoimmune disease, enzyme deficiency, infection, environmental factors, radiation, or surgery in 10%.
[15] Two to 5% of women with POI and a premutation in FMR1, a genetic abnormality, are at risk of having a child with fragile X syndrome, the most common cause of inherited intellectual disability.
It can include hormone replacement therapy, fertility management, and psychosocial support, as well as annual screenings of thyroid and adrenal function.
[7] POI contrasts with age-appropriate menopause in the age of onset, degree of symptoms and sporadic return to normal ovarian function.
Women with a germline BRCA1 mutation tend to have premature menopause as evidenced by the final amenorrhea appearing at a younger age.
[28] Impairment of the repair of DNA double-strand breaks due to a BRCA1 defect leads to premature ovarian aging in both mice and humans.
[32][33] The MCM8-MCM9 complex is likely required for the homologous recombinational repair of DNA double-strand breaks that are present during the pachytene stage of meiosis I.
In women homozygous for MCM8 or MCM9 mutations, failure to repair breaks apparently leads to oocyte death and small or absent ovaries.
[31][32] The diagnosis is based on age less than forty, amenorrhea, and two elevated serum follicle-stimulating hormone (FSH) and decreased estrogen measurements at one-month intervals.
[14] Researchers have investigated the use of a hormone called dehydroepiandrosterone (DHEA) in women with POI to increase spontaneous pregnancy rates.
[35] Given the inconclusiveness of potential benefits and risks of testosterone and DHEA supplementation, longer-term, randomized studies are warranted for women and girls with POI.
[40] Women with POI can develop symptoms of estrogen deficiency, including vasomotor flushes and vaginal dryness that respond to physiologic replacement of hormones.
The leading hormone replacement regimen recommended involves the administration of estradiol daily by either skin patch or vaginal ring.
This approach reduces the risk of pulmonary embolism and deep venous thrombosis by avoiding the first pass effect on the liver that is induced by oral estrogen therapy.
[42] Concerns of estrogen supplement are addressed in The US Medical Eligibility Criteria for Contraceptive Use, 2010 provides guidance for safety of contraceptive methods and include guidance for conditions associated with increased risk of thrombosis such as postpartum, history of thrombosis, thrombogenic mutations, systemic lupus erythematosus, diabetes, and hypertension.
[4] In observational studies, hormone replacement therapy in women with primary ovarian insufficiency and other causes of early menopause was associated with a lower risk of cardiovascular disease, increased bone density, and a reduced mortality.
[4] Patients face the acute shock of the diagnosis, associated stigma of infertility, grief from the death of dreams, anxiety and depression from the disruption of life plans, confusion around the cause, shame, insecurity and lowered self-esteem, anger in reflection of being letdown by the medical system, symptoms of estrogen deficiency, worry over the associated potential medical sequelae such as reduced bone density and cardiovascular risk, and the uncertain future that all of these factors create.
[47][48][49][50] It is important to connect women with POI to an appropriate collaborative care team because the condition has been clearly associated with suicide related to the stigma of infertility.
[10] Fuller Albright et al. in 1942 reported a syndrome with amenorrhea, estrogen deficiency, menopausal FSH levels, and short stature.