This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Perkins, R. B. Articles by Martin, K. A. Search for Related Content PubMed PubMed Citation Articles by Perkins, R. B. Articles by Martin, K. A.

Neuroendocrine Abnormalities in Hypothalamic Amenorrhea: Spectrum, Stability, and Response to Neurotransmitter Modulation¹

Reproductive Endocrine Unit, Reproductive Endocrine Sciences Center and National Center for Infertility Research, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts 02114

Address correspondence and requests for reprints to: Kathryn A. Martin, Reproductive Endocrine Unit, Massachusetts General Hospital, Bartlett Hall Extension 5, 55 Fruit Street, Boston, Massachusetts 02114.

To characterize the neuroendocrine patterns of abnormal GnRH secretion in hypothalamic amenorrhea (HA), 49 women with primary and secondary HA underwent frequent sampling of LH in a total of 72 baseline studies over 12–24 h. A subset of women participated in more than one study to address 1) the variability of LH pulse patterns over time; and 2) the impact of modulating opioid, dopaminergic, and adrenergic tone on LH secretory patterns.

The frequency and amplitude of LH secretion was compared with that seen in the early follicular phase (EFP) of normally cycling women. The spectrum of abnormalities of LH pulses was 8% apulsatile, 27% low frequency/low amplitude, 8% low amplitude/normal frequency, 43% low frequency/normal amplitude, 14% normal frequency/normal amplitude. Of patients studied overnight, 45% demonstrated a pubertal pattern of augmented LH secretion during sleep. Of patients studied repeatedly, 75% demonstrated at least 2 different patterns of LH secretion, and 33% reverted at least once to a normal pattern of secretion. An increase in LH pulse frequency was seen in 12 of 15 subjects in response to naloxone (opioid receptor antagonist). Clonidine (alpha-2 adrenergic agonist) was associated with a decrease in mean LH in 3 of 3 subjects. An increase in LH pulse frequency was seen in 4 of 8 subjects in response to metoclopramide (dopamine receptor antagonist), but the response was not statistically significant. Baseline abnormalities in LH secretion did not appear to influence response to neurotransmitter modulation. Conclusions: 1) HA represents a spectrum of disordered GnRH secretion that can vary over time; 2) LH pulse patterns at baseline do not appear to influence the ability to respond to neurotransmitter modulation; 3) Opioid and adrenergic tone appear to influence the hypothalamic GnRH pulse generator in some individuals with HA.

This article has been cited by other articles:

				J. G. Wang and R. A. Lobo The Complex Relationship between Hypothalamic Amenorrhea and Polycystic Ovary Syndrome J. Clin. Endocrinol. Metab., April 1, 2008; 93(4): 1394 - 1397. [Abstract] [Full Text] [PDF]

				J. E. Hall, J. P. Sullivan, and G. S. Richardson Brief Wake Episodes Modulate Sleep-Inhibited Luteinizing Hormone Secretion in the Early Follicular Phase J. Clin. Endocrinol. Metab., April 1, 2005; 90(4): 2050 - 2055. [Abstract] [Full Text] [PDF]

				C. K. Welt, J. L. Chan, J. Bullen, R. Murphy, P. Smith, A. M. DePaoli, A. Karalis, and C. S. Mantzoros Recombinant Human Leptin in Women with Hypothalamic Amenorrhea N. Engl. J. Med., September 2, 2004; 351(10): 987 - 997. [Abstract] [Full Text] [PDF]

				L. Falsetti, A. Gambera, L. Barbetti, and C. Specchia Long-Term Follow-Up of Functional Hypothalamic Amenorrhea and Prognostic Factors J. Clin. Endocrinol. Metab., February 1, 2002; 87(2): 500 - 505. [Abstract] [Full Text] [PDF]

				R. B. Perkins, J. E. Hall, and K. A. Martin Aetiology, previous menstrual function and patterns of neuro-endocrine disturbance as prognostic indicators in hypothalamic amenorrhoea Hum. Reprod., October 1, 2001; 16(10): 2198 - 2205. [Abstract] [Full Text] [PDF]