A 34-year-old woman, gravida 1 para 1, comes to the office for infertility evaluation. She has been trying to conceive for the past year, but her cycles have become increasingly irregular. Her last menstrual period was more than 3 months ago. Menses previously occurred every 27 days and lasted 4 days. The patient feels fatigued and has been waking at night due to feeling too warm. She has been married for 6 years and has a 4-year-old daughter who was delivered vaginally without complications. The patient has hypothyroidism, for which she takes levothyroxine. She has no previous surgeries. The patient smokes a pack of cigarettes daily but does not use alcohol or recreational drugs. Both parents have type 2 diabetes mellitus. BMI is 24 kg/m2. Vital signs are normal. Pelvic examination shows normal external genitalia; a small, mobile uterus; and normal bilateral ovaries. TSH is normal and a pregnancy test is negative. Which of the following would most likely be seen in this patient?
GnRH | FSH | Estrogen | |
Hypothalamic hypogonadism | ↓ | ↓ | ↓ |
Primary ovarian insufficiency | ↑ | ↑ | ↓ |
Polycystic ovary syndrome | ↑ | Normal | ↑ |
Normal ovulation | Normal | Normal | Normal |
Exogenous estrogen use | ↓ | ↓ | ↑ |
Primary ovarian insufficiency (POI), a form of hypergonadotropic hypogonadism, is the cessation of ovarian function at age <40. The condition is characterized by amenorrhea or oligomenorrhea and symptoms of decreased estrogen (eg, hot flashes, fatigue). Initial presentation is with irregular menses or infertility. Patients typically have a history of an autoimmune disorder (eg, hypothyroidism) or Turner syndrome. The decreased ovarian function results in low estrogen levels; this prevents the physiologic negative feedback mechanism, thereby causing increased levels of gonadotropin-releasing hormone (GnRH) and FSH at the hypothalamus and the pituitary, respectively. Infertility treatment for POI consists of either in vitro fertilization or oocyte/embryo donation.
(Choice A) Hypothalamic hypogonadism is characterized by low GnRH secretion and resultant low levels of FSH and estrogen. Typical presentation is also with oligomenorrhea or amenorrhea, but the condition is more likely in the setting of relative caloric insufficiency from decreased caloric intake (eg, eating disorders) or strenuous exercise. Patients with hypothalamic hypogonadism do not have associated menopausal symptoms because although estrogen is low, the ovaries often produce enough estrogen to offset vasomotor symptoms.
(Choice C) Polycystic ovary syndrome (PCOS) causes infertility by anovulation. Patients with PCOS have elevated GnRH, normal FSH, and elevated estrogen. In patients with PCOS, these hormone levels occur due to increased peripheral conversion of androgen to estrone. This leads to persistently elevated (ie, continuous high-frequency pulses) GnRH levels at the hypothalamus, which causes a preference for LH production (and normal to decreased FSH levels) at the pituitary. These patients typically have irregular menses, obesity, and signs of hyperandrogenism (eg, hirsutism, acne). Physical examination may show bilaterally enlarged ovaries.
(Choice D) Normal hormone levels would indicate ovulation, unlikely in a patient with irregular menses. Likely etiologies of infertility with normal laboratory values and normal menses are tubal blockage or male factor infertility.
(Choice E) Exogenous estrogen use decreases GnRH and FSH levels through negative feedback, thereby preventing ovulation. This patient has signs of hypoestrogenism (eg, hot flashes), not hyperestrogenism (eg, breast tenderness).
Educational objective:
Primary ovarian insufficiency, cessation of ovarian function at age <40, may present with infertility, irregular menses, and menopausal symptoms. It is characterized by elevated levels of gonadotropin-releasing hormone and FSH and low estrogen levels.