Osteopenia in women with hypothalamic amenorrhea: a prospective study.

Hypothalamic amenorrhea, a common disorder associated with abnormalities in gonadotropin pulsatility and subsequent estrogen deficiency, is usually transient, and treatment indications are unclear unless fertility is desired. To determine whether this disorder is associated with progressive bone loss, we studied 24 women with primary or secondary amenorrhea related to stress or simple weight loss, compared with 31 normal women of the same age. Amenorrheic women had significantly lower (P = .01) body fat (26.4 +/- 7.3 versus 30.6 +/- 4.7%) and higher (P = .0001) urine free cortisol levels (250 +/- 100 versus 140 +/- 50 nmol/day) than normals. Trabecular bone density in women with hypothalamic amenorrhea as assessed by spinal computed tomography was significantly (P = .001) lower than in normals (140.2 +/- 27.3 versus 175.1 +/- 24.6 mg K2HPO4/mL, respectively). Twenty of the 24 amenorrheic women had initial spinal bone density below the mean in normals, and in eight it was 2 standard deviations or more below the normal mean. Initial bone density correlated negatively with duration of amenorrhea (r = -0.489, P = .02) and positively with serum free testosterone levels (r = 0.517, P = .02). Prospective evaluation showed a decline in spinal bone density in those who were amenorrheic for fewer than 5 years. The slope of change in bone density correlated with initial weight, percent ideal body weight, and percent body fat (R2 = 0.597, P = .0003; R2 = 0.549, P = .0007; and R2 = 0.618, P = .0002, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Interpulse interval sequence of LH in normal men essentially constitutes a renewal process.

Luteinizing hormone (LH) is released from the anterior pituitary gland in an episodic pattern driven by pulses of gonadotropin-releasing hormone (GnRH) from the hypothalamus. Autocorrelation analysis of the sequence of interpulse intervals of LH secretion in normal men supports the hypothesis that the underlying mechanism driving LH secretion is a renewal process. That is, whatever "memory" the GnRH pulse generator (i.e., the hypothalamus or its antecedent neural drive) may have, it does not go back in time further than the preceding secretory pulse. Thus the hypothalamic timer starts over again each time there is a GnRH secretory episode.