4-HYDROXYCATECHOLESTROGEN METABOLISM RESPONSES TO EXERCISE AND TRAINING - POSSIBLE IMPLICATIONS FOR MENSTRUAL-CYCLE IRREGULARITIES AND BREAST-CANCER

Objective: To investigate the behavior of C4-substituted estrogens, th e so-called catecholestrogens, in response to acute exercise and train ing. The 4-hydroxyestrogens are known to have both a strong estrogenic potency and affinity for catechol-O-methyltransferase (COMT), the enz yme that deactivates catecholamines. Design: A prospective trial cover ing three menstrual cycles: a control cycle, a moderate training cycle , and a heavy training cycle. Participant(s): Six untrained, healthy, eumenorrheic women (mean pretraining maximum oxygen uptake: 40.9 +/- 4 .9 mL/kg per minute, body fat: 27.9% +/- 3.6%) volunteered for this st udy. Intervention(s): An incremental exercise test to exhaustion on a cycle ergometer, in the follicular and luteal phases, before and after a brief but exhaustive training program. Main Outcome Measure(s): Hor mone measurements included follicular and luteal phase plasma E(2), LH , catecholamines, PRL, total unconjugated and conjugated estrogens, to tal 4-hydroxyestrogens (4-OHE), and 4-hydroxyestrogen-monomethylethers (4-MeOE). Result(s): Pretraining baseline 4-OHE levels were significa ntly higher in the luteal phase (66 +/- 9 pg/mL; mean +/- SEM) than in the follicular phase (51 +/- 7 pg/mL). Pretraining and post-training baseline 4-MeOE values were below minimal detection limits (<35 pg/mL) . During incremental exercise, catecholamines, PRL, E(2) unconjugated and conjugated estrogens, 4-OHE, and 4-MeOE always increased (the incr eases in 4-OHE during exercise were more pronounced before training, c ontrary to the 4-MeOE being most increased after training). The baseli ne 4-MeOE:4-OHE ratio (a measure of catecholestrogen activity) signifi cantly increased with progressive training. Conclusion(s): Because 4-O HE have been shown to be able to control the hypothalamic gonadotropin oscillator and to stimulate the luteolytic prostaglandin PGF(2 alpha) , the acute exercise-induced increases of 4-OHE and their positive cor relation with lactate levels may indicate a key process in the pathoge nesis of exercise-associated menstrual irregularities. In addition, 4- OHE, when insufficiently O-methylated, are known to be capable of rais ing mutagenic superoxide free radicals and causing DNA damage that may lead to breast cancer. The results of the present study also may be o f significance for the apparent protective effects of sports participa tion against cancer of the breast.