The pathogenic mechanisms of<unk>  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. These result in a decrease of the ovaries general supply of eggs that normally lasts until an average age of 51 for age of age-appropriate menopause. Genetic causes such as Turner syndrome have initial<unk>  development but then ovaries degenerate rapidly during prenatal life, often leading to gonadal dysgenesis with streak ovaries. In those cases where<unk>  is associated with adrenal autoimmunity, histological examination almost always confirms the presence of an autoimmune oophoritis in which follicles are infiltrated by lymphocytes, plasma cells, and macrophages that attack mainly steroid-producing cells and eventually result in follicular depletion. In some women FSH may bind to the FSH receptor site, but be inactive. By lowering the endogenous FSH levels with ethinylestradiol (EE) or with a GnRH-a the receptor sites are free and treatment with exogenous recombinant FSH activates the receptors and normal follicle growth and ovulation can occur. (Since the serum Anti-Müllerian hormone (AMH) level is correlated with the number of remaining primordial follicles some researchers believe the above two phenotypes can be distinguished by measuring serum AMH levels. Genetic associations include genetic disorders, autoimmune diseases, enzyme defects, and resistant ovaries. Mutations in FOXL2 cause Blepharophimosis Ptosis Epicanthus inversus Syndrome (BPES). Premature<unk>  failure is part of the BPES Type I<unk> t of the syndrome but not of the BPES Type II<unk> t. DNA repair deficiency BRCA1 protein plays an essential role in the repair of DNA double-strand breaks by homologous recombination. Women with a germline BRCA1 mutation tend to have premature menopause as evidenced by the final menorrhea appearing at a younger age. BRCA1 mutations are associated with occult<unk> . Impairment of the repair of DNA double-strand breaks due to a BRCA1 defect leads to premature<unk>  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<unk>  failure, as well as chromosomal instability. MCM9, as well as MCM8, mutations are also associated with<unk>  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.
Primary ovarian insufficiency
Functional hypothalamic amenorrhea
Gonadotropin-resistant ovary syndrome
Androgen insufficiency syndrome
Hypergonadotropic hypergonadism
Polycystic ovary syndrome
Anovulation
Lactational amenorrhea