Amenorrhea is the absence of menstruation attributed to primary or secondary conditions. The most common cause of amenorrhea is pregnancy. Primary amenorrhea is defined as absence of menarche by age 16 years with normal pubertal growth and sexual development, or a girl who has not started menstruation within 3 years of the first signs of puberty.1,2 There are many causes associated with primary amenorrhea such as anatomic defects, pituitary causes, endocrine gland disorders, and congenital abnormalities. Secondary amenorrhea is defined as a delay of at least 3 periods in a row with previous regular menses for 3 months or irregular menses for 6 months.2 Causes of secondary amenorrhea may include stress, eating disorders, hyperprolactinemia, chemotherapy, or irradiation, among others (Table 1).3
This patient is considered obese based on her current BMI of 30.91 kg/m2, which is at the 97th percentile, and current weight of 102.4 kg, which is at the 100th percentile based on weight for age. The risk of developing hyperandrogenemia, hyperinsulinemia, and/or anovulation is highest in obese subjects.4 On physical exam, acanthosis nigricans is noted at the neck region. Acanthosis nigricans can be evidence of insulin resistance as well as androgen excess.5 Among adolescent patients, obesity has been associated with the development of hyperandrogenemia and hyperinsulinemia.6
Laboratory tests are ordered for this patient to rule out the main causes of primary amenorrhea (Table 2). Laboratory findings are significant for an elevated free and total testosterone with hyperinsulinemia, as well as an increase in the luteinizing hormone (LH) to follicle stimulating hormone (FSH) ratio of 6.9:4.9, which is approximately 2:1.
At follow-up 4 weeks later, lab results were discussed with the patient and parent. The patient has continued doing well without cyclic pelvic pain, and still has no periods. Review of systems and the physical exam remained the same with a continued elevated BP of 144/86 mm Hg. The individual FSH and LH levels were within normal range, which ruled out ovarian failure. However, there was a slight increase in the LH to FSH ratio. The increase in the LH may cause an increase in the testosterone level, which was present in her laboratory findings. Causes for elevated testosterone levels include Cushing syndrome, ovarian tumors, thyroid disorders, adrenal tumor, ovarian tumor, or hyperandrogenism. Abnormal levels of prolactin (PRL) and thyroid stimulating hormone (TSH) can cause amenorrhea resulting from hyperprolactinemia or thyroid gland dysregulation, respectively, which were both within normal limits for this patient, indicating these were not the cause for this patient’s primary amenorrhea.7
At initial presentation, a pelvic ultrasound had been ordered because it could confirm the presence or absence of a uterus and identify structural abnormalities of the reproductive tract organs. This patient’s ultrasound confirmed the presence of a postmenarchal uterus with peripherally placed follicles throughout both ovaries (Figure 1A and 1B).
At this point, the girl’s physicians had confirmed hyperandrogenism attributed to an elevated free and total testosterone level, and a slightly elevated LH to FSH ratio of 2:1. Primary amenorrhea was present with developed secondary sexual characteristics to include Tanner stage IV for breast and pubic hair development in this obese 14-year-old patient for the last 4 years. The patient showed evidence of hyperinsulinemia based on laboratory finding of elevated insulin and physical exam finding of acanthosis nigricans. Finally, her ultrasound demonstrated a postmenarchal female with polycystic ovaries.
Based on the above evidence, the diagnosis was made of primary amenorrhea secondary to polycystic ovarian syndrome (PCOS; Table 3).