Snapshot A 37-year-old woman reports vaginal dryness and menstrual irregularities. She had an intrauterine device (IUD) placed for 5 years and now wishes to conceive with her husband. While they have only been trying for 4 months, she has not had a regular menstrual period since removing the IUD. She denies hot flashes. On physical exam, she has a normal stature and normal BMI, but has a notably atrophic vagina. Laboratory results reveal low estradiol and high follicle-stimulating hormone, suggestive of primary ovarian insufficiency. Introduction Hypergonadotropic hypogonadism before 40 years of age also known as premature ovarian failure Characterized by loss of oocytes ↓ estrogen production infertility Pathogenesis accelerated follicle depletion normally, follicle depletion is completed around 51 years of age (average age of menopause) rate of follicle depletion may be accelerated by genetic disorders and toxins to the ovary toxins galactose metabolites chemotherapy/radiation therapy viruses (mumps and CMV) causing oophoritis decreased steroid production without oocyte loss Epidemiology 1 in 250 by age 35 years 1 in 100 by age 40 years Associated conditions and risk factors chromosomal defects (e.g., Turner syndrome and fragile X syndrome) galactosemia exposure to radiation autoimmune disease Presentation Symptoms are similar to menopause change in menstruation oligomenorrhea amenorrhea failure to return to normal menstruation after stopping contraceptives or following a pregnancy difficulty conceiving estrogen deficiency hot flashes vaginal dryness Physical exam vaginal atrophy features of Turner syndrome short stature webbed neck squarely shaped chest Evaluation Diagnosis is made in women younger than 40 years of age with irregular menses and high follicle-stimulating hormone (FSH) Labs ↑ FSH and lutenizing hormone (LH) ↓ estradiol Transvaginal ultrasound typical findings enlarged cystic ovaries findings in Turner syndrome streak ovaries Differential Pregnancy Hyperprolactinemia Other cause of female infertility Treatment Estrogen-progestin replacement therapy for prevention of osteoporosis symptomatic control of hot flashes and vaginal dryness prevention of coronary artery disease recommended until after age 50 Assisted reproductive technologies in vitro fertilization with donor oocytes or donor embryos Prognosis, Prevention, and Complications Complications ↓ quality of life earlier onset osteoporosis if primary ovarian insufficiency is not identified early