A contrasting problem can be when a girl never begins menstruation due to a genetic condition causing primary amenorrhea. Causes
The cause of POI is idiopathic in 90% of cases. Some cases of POI are attributed to autoimmune disorders such as autoimmune oophoritis, Hashimoto thyroiditis, Addison disease, type I diabetes mellitus, pernicious anemia, genetic disorders such as Turner syndrome and Fragile X syndrome, metabolic defects, and enzyme defects. One study showed a strong correlation between incidence of POI and certain variants in the inhibin alpha gene. Chemotherapy and radiation treatments for cancer can sometimes cause POI. The effect of chemotherapy or radiation is variable and in a mouse model, with results consistent with observations in humans, cyclophosphamide can result in an 87% reduction in primordial follicles 72 hours after administration. Women who have had a hysterectomy tend to go through menopause early and have a nearly twofold increased risk of POI. Almost any pelvic surgery has the potential to damage the ovary by affecting its blood supply or causing inflammation in the area resulting in POI. Galactosemia
Women who have inherited classic galactosemia (galactose intolerance) may develop primary ovarian insufficiency. Mechanism
The pathogenic mechanisms of POI are highly heterogeneous and can be divided into four major categories: follicular migration defect early in embryogenesis; an early decrease in the primordial follicles; increased follicular death; and altered maturation or recruitment of primordial follicles.
BRCA1 mutations are associated with occult POI. Impairment of the repair of DNA double-strand breaks due to a BRCA1 defect leads to premature ovarian aging in both mice and humans.In addition to BRCA1, the MCM8-MCM9 protein complex also plays a crucial role in the recombinational repair of DNA double-strand breaks. In humans, an MCM8 mutation can give rise to premature ovarian failure, as well as chromosomal instability. MCM9, as well as MCM8, mutations are also associated with ovarian failure and chromosomal instability. 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. Diagnosis
The diagnosis is based on age less than forty, amenorrhea for four months or more, and two elevated serum follicle-stimulating hormone (FSH) measurements at one-month intervals. The anterior pituitary secretes FSH and LH at high levels to try to increase the low estrogen levels that are due to the dysfunction of the ovaries. Typical FSH in POI patients is over 40 mlU/ml (post-menopausal range). Treatment
Fertility
Between 5 and 10 percent of women with POI may become pregnant with no treatment. As of 2016 no fertility treatment has been found to effectively increase fertility in women with POI, and the use of donor eggs with in-vitro fertilization (IVF) and adoption are a means of achieving parenthood for women with POI.