“The role of endogenous opiates in athletic amenorrhea” Mary Samuels, M.D., Charlotte Sanborn, Ph.D., Frederick Hofeldt, M.D., and Richard Robbins, M.D. Presented by Latesha Walls February 18, 1999

Background Female athletes frequently have abnormal menstrual cycles It has been proven that abnormal gonadotropin secretion can occur in highly trained athletes However, eumenorrheic athletes can also have abnormal gonadotropin-releasing hormones

Background cont. Studies have shown that amenorrheic runners have decreased LH and FSH levels compared to eumenorrheic runners Endogenous opiates suppress LH secretion in normal women Elevated opiates suppress normal LH secretion in female runners and this may contribute to menstrual disorders

Purpose To investigate the mechanism of amenorrhea in runners by comparing their LH, FSH, and PRL responses with releasing hormones in the presence or absence of opiod antagonists

Hypothesis 1. Amenorrheic athletes would have lower LH, FSH, and PRL levels than eumenorrheic athletes 2. Amenorrheic athletes would have abnormal gonadotropin and PRL responses to GnRH and thyrotropin-releasing hormone at rest and during exercise 3. Naloxone would stop these abnormalities

Overall hypothesis Exercise elevates endogenous opiods, which suppress gonadotropin and increase PRL levels. These abnormalities could lead to amenorrhea and eventually hypogonadism- induced osteoporosis

Subjects Twelve runners (six eumenhorreic and six amenorrheic) Eumenorrheic runners- runners whose cyclic menses occur every days for at least a year Amenorrheic runners- 3 or less periods per year with a lack of menstrual or intermenstrual bleeding for at least 6 months before the study The subjects ran 30 or more miles per week for at least a year

Studies Five studies were performed –Treadmill test to determine maximum oxygen uptake –TRH and GnRH was taken at rest by being inserted into the blood stream and taken every 15 minutes for 90 minutes –At rest, naloxone was injected and then TRH and GnRH injected and measured in the blood stream

Studies cont. –TRH and GnRH were injected after the treadmill test –Naloxone was injected before the treadmill test and TRH and GnRH afterwards

Results The two groups were similar in maximum heart rate and VO2 max during exercise There was no significant difference between the groups in basal hormone levels including LH, FSH, and PRL FSH and LH increased after TRH and GnRH was injected at rest, regardless of naloxone’s presence PRL increased when naloxone was given before TRH and GnRH

Results cont. There was a slight change in hormone levels during exercise alone In eumenorrheic runners, naloxone increased LH levels slightly over those during exercise without naloxone, but did not alter FSH or PRL levels in either group In either group, naloxone had no effect on changes in hormone levels after postexercise TRH and GnRH tests

Discussion The study did not confirm any of the hypotheses stated Amenorrheic runners did not have significant alterations in basal, postexercise, or stimulated hormone levels compared to eumenorrheic runners Opiod blockade by naloxone had little effect

Limitations There was a small sample size within the two groups The subjects were highly trained women who were conditioned to the effects of endogenous opiates Exercise-induced amenorrhea may be a disorder that may involve opiod-induced hormone abnormalities