Review Question - QID 218496

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Amenorrhea / Anovulation Introduction Causes QID: 218496 (M1.OMB.74)

QID 218496 (Type "218496" in App Search)

A 17-year-old girl presents to her gynecologist with amenorrhea for the past 4 months. The patient had menarche at age 14 and has previously had regular menstrual cycles. She reports some increased stress due to the upcoming national track and field competitions, for which she has been preparing. She denies headache, galactorrhea, or increased hair growth. She does have acne; however, she does not feel that her acne has gotten worse in the past year. She has no other significant past medical or surgical history, including no recent history of uterine instrumentation. Her family history is significant for breast cancer in her maternal grandmother at the age of 65 years. She is sexually active with 2 male partners and consistently uses barrier contraception. She does not drink alcohol, smoke tobacco, or use other recreational drugs. Her temperature is 98.6°F (37.0°C), blood pressure is 110/65 mmHg, pulse is 65/min, respirations are 16/min, and O2 saturation is 99% on room air. Her body mass index (BMI) is 18.2 kg/m^2. Physical examination is unremarkable. A urine pregnancy test is negative. Laboratory studies show:

Serum:
Thyroid-stimulating hormone (TSH): 2.0 mIU/L
Prolactin: 7 ng/mL

Which of the following additional hormonal changes would be expected in this patient compared to a normal patient of her age?

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This patient with a history of increased energy expenditure who presents with secondary amenorrhea, normal prolactin, and normal TSH most likely has functional hypothalamic amenorrhea (FHA). Patients with FHA would be expected to have decreased levels of gonadotropin-releasing hormone (GnRH), luteinizing hormone (LH), follicle-stimulating hormone (FSH), and estradiol with a normal LH to FSH ratio.

FHA is characterized by chronic anovulation that is not due to organic causes. Decreased caloric intake, excessive energy expenditure, and/or stress can lead to a functional reduction in hypothalamic GnRH secretion. In turn, this leads to reduced LH pulse frequency and decreased levels of FSH. Insufficient levels of LH and FSH lead to inability to maintain full folliculogenesis and ovulatory dysfunction. Clinicians must first exclude anatomic and organic etiologies of amenorrhea before pursuing a diagnosis of FHA. Diagnosis is based on findings of amenorrhea, low gonadotropins, and low estradiol in the setting of a precipitating factor. Cortisol levels may be elevated if the cause of FHA is stress, but the circadian pattern of cortisol secretion is preserved. Treatment includes correcting energy imbalance to improve hypothalamic-pituitary-ovarian (HPO) axis dysfunction, psychological support, and short-term use of estradiol with cyclic oral progestin therapy.

Gordon et al. discuss the Endocrine Society recommendations for the diagnosis and treatment of FHA. The authors find that oral contraceptives do not improve bone mineral density in patients with FHA. The authors also note that although bisphosphonates have a small but significant effect in improving bone mineral density, bisphosphonates are retained for years in the human skeleton and are potential teratogens. The authors recommend against the use of oral contraceptives and bisphosphonates to improve bone mineral density in patients with FHA.

Figure A presents the possible answer choices for this question. Changes in the levels of GnRH, LH, FSH, LH/FSH ratio, and estradiol are shown in the table.

Incorrect Answers:
Answer 2: Decreased GnRH, decreased LH, decreased FSH, increased LH/FSH ratio, and decreased estradiol is consistent with nonclassical congenital adrenal hyperplasia (CAH). Nonclassical CAH is a group of autosomal recessive disorders in which there is impaired cortisol synthesis leading to increased postnatal androgen excess. This leads to dysregulation of the HPO axis. Clinically, women with nonclassical CAH can present with amenorrhea, acne, hirsutism, and infertility.

Answer 3: Normal GnRH, normal LH, normal FSH, normal LH/FSH ratio, and normal estradiol are consistent with Mullerian agenesis (Muller-Rokitansky-Kuster-Hauser syndrome). Mullerian agenesis is a cause of primary amenorrhea and is characterized by underdevelopment of the vagina and/or uterus. Patients otherwise have typical growth and pubertal development; therefore, no hormonal disturbances would be expected.

Answer 4: Increased GnRH, increased LH, decreased FSH, increased LH/FSH ratio, and increased estradiol is consistent with polycystic ovary syndrome (PCOS). PCOS is a disorder characterized by anovulation, high androgen levels, and ovarian cysts. In PCOS, hyperinsulinemia can increase GnRH pulse frequency and increased LH, which leads to increased ovarian androgen production. PCOS can present clinically with irregular menstrual cycles, hirsutism, acanthosis nigricans, and acne.

Answer 5: Increased GnRH, increased LH, increased FSH, decreased LH to FSH ratio, and decreased estradiol is consistent with primary ovarian insufficiency (POI). Patients with ovarian insufficiency have premature depletion or dysfunction of ovarian follicles and cessation of menses before the age of 40 years. Patients with primary ovarian insufficiency have decreased estradiol production, which reduces feedback inhibition on the HPO axis leading to increased GnRH, LH, and FSH. Similar to normal menopause, FSH is usually elevated more than LH, leading to a decreased LH to FSH ratio. POI presents clinically with irregular menstrual cycles or amenorrhea. Secondary effects of estrogen deficiency in POI include hot flashes, vaginal dryness, osteoporosis, and increased cardiovascular disease risk.

Bullet Summary:
Functional hypothalamic amenorrhea presents with low levels of gonadotropin-releasing hormone (GnRH), luteinizing hormone (LH), follicle-stimulating hormone (FSH), and estradiol in the setting of decreased caloric intake, excessive energy expenditure, or increased stress.