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Vol. 83, Issue 5, 1551-1556, 1997
Interuniversity Project on Reproductive Endocrinology in Women and Exercise, 1 Department of Applied and Experimental Reproductive Endocrinology, B-3000 Leuven 3, Belgium; 2 Department of Biochemical and Clinical Endocrinology, Medical University of Lübeck, D-23538 Lübeck, Germany; and 3 Department of Movement Sciences, Faculty of Health Sciences, University of Maastricht, NL-6200 MD Maastricht, The Netherlands
ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
ACKNOWLEDGEMENTS
FOOTNOTES
REFERENCES
ABSTRACT 
De Crée, Carl, Peter Ball, Bärbel
Seidlitz, Gerrit Van Kranenburg, Peter Geurten, and Hans A. Keizer.
Effects of a training program on resting plasma
2-hydroxycatecholestrogen levels in eumenorrheic women.
J. Appl. Physiol. 83(5):
1551-1556, 1997.
Catecholestrogens (CE) represent a major
metabolic pathway in estrogen metabolism. Previous information on CE
and training is limited to two cross-sectional studies that did not
involve standardized training. Our purpose, by means of a prospective design, was to evaluate the effects of a brief, exhaustive training program on resting plasma concentrations of 2-hydroxy CE. The experimental design spanned two menstrual cycles: a control cycle and a
training cycle. The subjects were nine previously untrained, eumenorrheic women [body fat: 24.8 ± 1.0 (SE) %]. Data
were collected during the follicular (FPh) and the luteal phases (LPh).
Posttraining FPh and LPh tests were held the day after the last day of
a 5-day period of training on a cycle ergometer. Total
2-hydroxyestrogens (2-OHE) averaged 200 ± 29 pg/ml during the FPh
and 420 ± 54 pg/ml during the LPh
(P < 0.05). Levels of total
2-methoxyestrogens (2-MeOE) were 237 ± 32 pg/ml during the FPh and
339 ± 26 pg/ml during the LPh (P < 0.05). After training, although the plasma levels of 2-OHE
significantly decreased (
21%;
P < 0.05) during the LPh, the actual
CE formation (as estimated from the 2-OHE-to-total estrogens ratio)
increased (+29%; P < 0.05). CE activity, as expressed by the 2-MeOE-to-2-OHE ratio, showed
significantly higher values in both phases (FPh, +14%; LPh, +13%;
P < 0.05). At the same time, resting
levels of norepinephrine (NE) were increased by 42%
(P < 0.05). CE strongly inhibit
biological decomposition of NE by catechol-O-methyltransferase (COMT).
Results of the present study suggest that, in response to training, CE
are increasingly competing with the enzyme COMT, thus preventing
premature NE deactivation.
amenorrhea; anovulation; catecholamines; catechol-Omethyltransferase; estrogens; 2-hydroxylase
INTRODUCTION IT HAS BEEN EXTENSIVELY DOCUMENTED that acute physical
exercise and training in women provoke significant changes in the
plasma concentrations of sex hormones (5). Strenuous exercise leads to
an increased risk of irregular menses and anovulation. Premature osteoporosis has been identified as the most worrisome long-term effect
(12). Despite the many published reports, the underlying mechanisms of
the initial hypoestrogenemia are still unknown because of the many
confounding variables (see Ref. 21 for a review). Some years ago, it
was hypothesized that hypoestrogenemia in female athletes is not merely
a secondary effect of hypothalamic disruption of the
gonadotropin oscillator, as previously assumed, (30) but
rather, perhaps, a primary consequence of increased
catecholestrogen (CE) formation. As a consequence, normal gonadotropin
release may be inhibited by negative CE feedback (23, 24).
CE are very unstable substances with both catecholamine and estrogen
capabilities and represent the major metabolic pathway of estrogens.
The name CE refers to the C2- and
C4-hydroxylated metabolites of estrone
(E1) and estradiol
(E2) as well as to their O-methylated compounds. Most available
research on CE has focused on either 2-hydroxyestrone
(2-OHE1) or 2-hydroxyestradiol
(2-OHE2). The reason for this
choice is that the C4-hydroxylated
estrogen metabolites circulate in smaller plasma concentrations and
have a shorter half-life than the
C2-hydroxylated estrogens, which make
their analysis even more critical than that of
C2-hydroxylated estrogen metabolites.
Because of the considerable difficulties involved in all CE-analysis
procedures, it should not be surprising that only two published studies
(26, 27), each with a cross-sectional design and partially the same
subjects, are available that have examined the effects of physical
training on 2-hydroxyestrogens. These authors found that, in the most
strenuously training swimmers, plasma
E2 concentrations were the lowest
and 2-hydroxyestrogen levels were simultaneously the highest. These
results suggested that physical training induces an increased turnover
from primary estrogens to CE. However, these authors did measure only
the nonmethylated 2-hydroxyestrogens.
After the formation of CE, the next biochemical step, the conversion of
the 2-hydroxyestrogen to the
2-hydroxyestrogen-monomethylethers or 2-methoxyestrogens
(2-MeOE), is catalyzed by
catechol-O-methyltransferase (COMT;
for a detailed overview of the metabolic pathways, see Ref. 9). Because
CE competitively bind to COMT, the enzyme that decomposes
catecholamines (1, 2), it has been speculated that these CE would
prevent norepinephrine (NE) from premature decomposition (9). The
information provided by measurement of 2-hydroxyestrogens alone is too
limited to investigate the role CE may play. To have some indication
concerning the actual physiological activity of CE, we also
determined 2-MeOE and catecholamines.
Our purpose was to obtain preliminary data on the responses of
2-hydroxyestrogens and their monomethylethers in untrained, normally
menstruating women after brief, standardized physical training. This
represents a first step in thoroughly examining the CE sequence within
the feedback system proposed earlier (9). In the present study, we have
also computed the 2-hydroxyestrogen-to-estrogens and the
O-methylated-to-nonmethylated CE
ratios, as introduced previously (10). In the absence of radiolabeling
techniques, the formation and activity of CE may be estimated from
these ratios. We hypothesized that exercise in women increases both the
turnover from primary estrogens into CE and the activity of CE (binding to COMT).
MATERIALS AND METHODS
O2),
carbon dioxide production
(CO2), and minute ventilation (E) were computed from
continuously measured values for breathing rate, tidal volume, and
expiratory gas concentrations by using a precalibrated on-line system
(Oxycon 
, Mijnhardt-Jäger, Bunnik, The Netherlands).
A brief but exhaustive graduated training program was designed (Fig.
1). The training period started 5 days
before the second FPh test and again 5 days before the second LPh test.
Training was adjusted daily. Each subject had to report for a
standardized lab training session on a cycle ergometer. Training
started each day with 6 min of cycling at 100 W, and exercise intensity
was increased 25 W at 2-min intervals until the individual's maximum of that day was reached. This allowed us to accommodate the daily training program to the individual's maximal physical working capacity
(MPWC) on that day. MPWC was defined on the basis of the subject's
maximal power and heart rate. Immediately after the maximal exercise
test, the subject was allowed to recover for 10 min at 50% MPWC.
Afterward, the subject switched to interval training. This part of the
training consisted of a 2-min series at 90% of the individual's MPWC,
followed each time by 2 min at 50% MPWC. Whenever the subject failed
to continue (when she was not able to raise her pedaling rate again
over 60 revolutions/min), the exercise intensity was lowered to 80%
MPWC, and a 2-min interval series would continue at this intensity,
followed again each time by a 2-min recuperation, still at 50% of the
individual's maximum, until the individual failed to continue at 80%
MPWC. If necessary, each time the individual failed, intensity was
lowered by 10% in a way similar to that described above. The training
session stopped when the subject reached complete voluntary exhaustion (defined as the inability to keep the pedaling rate >60
revolutions/min at any intensity). This was usually after ~90 min of
exercise.
O2 max, maximal
O2 consumption.
Blood hormone and biochemical analysis. Blood for hormone analysis was drawn from the antecubital vein through a venous indwelling catheter by means of disposable syringes (20 ml) between days 7 and 10 in the FPh and between days 23 and 25 in the LPh. Analysis day was identical to the day of the exercise test. In the training phase, this day coincided with the first day after completion of the 5-day training period. Blood samples for CE analysis were thus obtained 5-7 days before ovulation and 10-14 days after ovulation. Blood samples were collected in prechilled lyophilized EDTA glass tubes stored in an ice bath at 2°C. Blood samples for estrogen and CE determination were immediately centrifuged at 2,000 g for 10 min at 4°C, deep-frozen in liquid nitrogen, and stored at
80°C until assayed.
Free, i.e., the unconjugated, 2-hydroxyestrogen fraction in plasma is
frequently near or below the detection limit of normal CE-assaying
procedures (3). Therefore, to ensure validity and accuracy, we
determined "total" 2-hydroxyestrogens (2-OHE), i.e., the sum of
the unconjugated and conjugated fractions of
2-OHE1 and
2-OHE2. A similar approach was
used for the total 2-OHE-monomethylethers (i.e, 2-MeOE).
2-OHE and 2-MeOE were determined together in one assay procedure, as
detailed previously (10).
To have a comparable measurement, we also determined total estrogens
(i.e., E), being the sum of the conjugated and unconjugated E1 + E2 fractions. Intra-assay
coefficients of variation for 2-OHE and 2-MeOE are <10%. The
interassay precision, as determined from pool plasma, resulted in a
coefficient of variation of <17.2% for 2-OHE and 2-MeOE. The lower
limit of detection for all CE assays was ~6 pg/ml.
The plasma for the determination of all other hormones was pipetted in
3-ml Eppendorf cups, quickly frozen in liquid nitrogen, and stored at
80°C until analysis. Plasma LH concentrations were determined by using an immunoradiometric assay purchased from Serono
(Geneva, Switzerland). The sensitivity is 0.4 mIU/ml, and the
interassay coefficient of variation is <10%. All samples were analyzed in duplicate in the same assay and were batched so that pre-
and postexercise samples for both FPh and LPh were analyzed in the same
assay.
Catecholamines were determined by electrochemical determination after
separation by using high-performance liquid chromatography. These
procedures, as well as the equipment and chemicals used, have all been
described previously (10). The respective interassay coefficients of
variation were 4.5% for NE, 11.3% for epinephrine (Epi), and 11.8%
for dopamine (DA). The intra-assay coefficient of variation was <10%
for each catecholamine.
Total protein was determined by the biuret method, and hemoglobin was
determined spectrophotochemically with the hemoglobin cyanide method.
Hematocrit was determined by the microcentrifuge method, and blood
lactate was determined with an electrical-chemical-enzymatic method by
using a semiautomatic lactate analyzer (model 640, Kontron, Zurich,
Switzerland).
Statistical analysis.
Results before and after training were compared by using paired
t-tests. Comparisons between different
menstrual phases were made by a two-way, mixed-model, repeated-measures
analysis of variance. An 
-level of 0.05 was set a priori. Phase,
group, phase-group (interactive), and subject effects were evaluated
independently by maximum likelihood procedures. This technique has
proved to be more robust than conventional statistics in the presence
of bias due to nonnormal distribution, missing values, radioimmuoassay imprecision, and so on (6, 8, 16). Values for comparisons of group
means are given as means ± SE.
RESULTS
O2
(O2 max) was
significantly lower (41.5 ± 1.4 vs. 45.7 ± 1.5 ml · kg
1 · min1
in LPh vs. FPh, respectively; P < 0.05). Power increased with training in both phases, but
O2 max
decreased in the FPh to 42.5 ± 1.1 ml · kg1 · min1.
Posttraining LPh values (43.5 ± 1.1 ml · kg1 · min1)
were higher than pretraining LPh values, although still lower than in
the FPh (Table 1). There were no
significant changes in body mass that could account for these
differences.
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53%) and 2-OHE
(21%) were only observed in the LPh (Table
3). To have a rough estimation of CE
production and turnover, we calculated 2-OHE-to-E (2-OHE/E) and
2-MeOE-to-2-OHE (2-MeOE/2-OHE) ratios. 2-OHE/E (measurement of CE
formation) increased after training but only in the LPh (+29%,
P < 0.05). 2-MeOE/2-OHE (correlates
with COMT activity) increased in both the posttraining FPh and LPh (+14
and +13%, respectively; P < 0.05).
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DISCUSSION
80°C, we have employed maximal
guarantees to protect the samples from premature decomposition (13) and
have avoided some of the flaws of previous studies. Furthermore, the
present study offers specific data on the metabolic pathway of CE by
including measurements of the monomethylethers. This is particularly
important for our hypothesis because without these values it is hardly
possible to speculate on the actual physiological activity of CE.
Because CE are heavily conjugated, and the inactivity of the conjugated fraction has not been proved, we have used the sum of conjugated and
unconjugated fractions in this study. Most literature on estrogens and
exercise only reports the unconjugated fraction of
E2. We believe, however, that this
method would be inappropriate here because it would be an extremely
difficult method of obtaining any indication whatsoever on the transfer
toward total CE.
Standard laboratory data on CE that have been published previously have
all been based on very few subjects because of the laborious and
expensive assaying procedures (13). Our values for basal total CE
appear to be lower than ranges previously suggested for 2-hydroxy CE in
some of the previous papers (3, 13). In fact, values were akin to
assumed ranges for the mere unconjugated fraction in sedentary women.
The data were also lower than our estimated reference laboratory values
calculated from our earlier studies (3). They were, however, within the
ranges of our pool values. Although, we do not have any conclusive
explanation for these differences, it must be emphasized that sample
collection and assaying procedures were conducted with extreme rigor.
In addition, most data in the literature that mention CE concentrations date back 15 years or more. In these studies, plasma collection and
treatment often did not involve immediate freezing by liquid nitrogen,
and samples were mostly stored at 20°C only. The type of
training was chosen because studies from Keizer et al. (20) had shown
earlier that by using this aerobic and anaerobic training schedule it
was possible to provoke a disturbance of normal gonadotropin pulsatility.
Catecholamines and training.
Although posttraining samples were obtained under resting conditions
(at least 24 h after the last training had taken place), plasma NE
levels were significantly higher than before training. This finding is
important because there is substantial evidence in support of
noradrenergic mediation of LH release (18). Also, acute
exercise-induced NE concentrations are known to be higher in
hypoestrogenemic female athletes (7). However, no previous explanation
has been offered as to why training produces higher resting levels of
NE. It is speculated, therefore, that this is a direct effect of the
increased competition by CE for COMT, as suggested by the increased
resting 2-MeOE/2-OHE values found in both menstrual phases. Recent
experiments in rats have demonstrated that CE indeed increase NE
concentrations via the above-mentioned mechanism (25).
Primary estrogens and training.
Resting LPh plasma E levels, after a brief, exhaustive training
program, were significantly lower. This finding is in association with
many earlier findings on unconjugated
E2 behavior (19, 20, 27). Only a
limited number of studies, for example by Bullen and colleagues (5),
did not find any differences in resting plasma
E2 after a 2-mo period of
endurance training. However, the training intensity of the subjects
involved in that trial appeared to be lower than in most studies,
including ours. Of considerable importance is a comparison with the
studies by Russel et al. (26, 27) because they are the only other group
of investigators who has reported responses of plasma CE to training.
Like Bullen et al. (5), these authors did not find any differences in
simple estrogens after strenuous training. However, this should not be surprising because their subjects were already highly trained, and many
of them were oligomenorrheic and estrogen deficient before the actual
trial started.
CE and training.
In the present study, only the LPh levels of CE (both 2-OHE and 2-MeOE)
were significantly lower than pretraining values. Conversely, Russel
and colleagues (26, 27) observed that, in response to several months of
strenuous long-distance training, at the same time resting
E2 levels were unaltered (although
lower than in controls) and unconjugated
2-OHE1 levels increased.
Any explanation for the discrepancy between our results and theirs for
CE responses will be more speculative than for the primary estrogens.
Obviously, this is also because 2-OHE responses to exercise are far
less well documented than are those of primary estrogens. We suggest
that in highly trained aerobic athletes, an increased turnover, or an
unlikely decreased hepatic clearance, would explain their results. We
may not have observed a similar effect because our subjects were
previously untrained, the training in the present study also involved
anaerobic exercise, there are differences in body composition between
our subjects and theirs (their subjects were leaner), and because of
the much wider age range of the subjects in their study (from
perimenarcheal to 35 yr of age). Furthermore, it is likely that
differences between the results of their study and ours are caused by
the introduction of more rigorous sample-treatment procedures, which
became possible because of recent advances in biochemical knowledge.
Physiology of CE.
It was speculated before that CE would participate in energy metabolism
in response to heavy exercise by preventing NE from premature
decomposition by COMT. When more primary estrogens are converted into
CE, this is likely to produce lower circulating plasma estrogen
concentrations and eventually hypoestrogenemia, unless estrogen
production would simultaneously increase. This is unlikely to happen.
Therefore, exercise-induced menstrual problems might rather be the
consequence of hypoestrogenemia than vice versa. However, a second
simultaneously active mechanism causing hypoestrogenemia has also been
suggested. This involves the documented stimulatory action of CE on
prostaglandin F2
(15, 22). This
prostaglandin is known to dramatically increase in response to exercise
(11) and to exert strong luteolytic effects on the developing corpus
luteum. Furthermore, the low amounts of body fat previously considered
as a key process in the development of exercise-induced amenorrhea may
induce crucial changes in CE metabolism. Indeed, the
16-hydroxylation that dominates estrogen metabolism in women with
higher percentages of body fat shifts to 2-hydroxylation (i.e.,
formation of CE) in women with lower percentages of body fat. This was
already observed in obese sedentary women (14) and was recently
confirmed in female athletes (28).
To the best of our knowledge, no data on the actual formation or
activity of 2-hydroxyestrogens in response to training are available.
We observed that before training there seemed to be no differences in
the rate of CE formation (expressed as 2-OHE/E) between menstrual
phases. However, the rate of methylation of CE (and thus COMT activity,
expressed as 2-MeOE/2-OHE) is apparently higher during the FPh. Both
formation (but only in the LPh) and activity (in both phases) of CE
seem to be boosted by training. The two studies by Russel et al. (26,
27) provided enough data to compute the (unconjugated) CE-to-estrogen
ratio as a measurement of CE formation. This leads to results of actual
CE formation that are in agreement with those of the present study.
In conclusion, the results of the present study show that brief periods
of exhaustive training in previously untrained eumenorrheic women
decreased the total primary estrogen levels but were unable to raise
total CE levels. A longer period of intensive training is probably
needed to provoke increments in resting CE levels. However, despite the
absence of significant changes in plasma CE concentrations, there
appears to be an increase in their formation and especially in their
activity. We suggest that the training-induced increases in resting NE
levels, previously shown to inhibit hypothalamic gonadotropin-releasing
hormone release (4), may be a direct effect of increased CE activity
(ie., competition for COMT). However, as yet there is not sufficient
evidence either to accept or to reject the hypothesis that assigns a
crucial role to CE in the etiology of exercise training-induced
hypoestrogenemia.
ACKNOWLEDGEMENTS
We are indebted to all of the women who kindly volunteered for this study. We gratefully acknowledge Drs. Alex Vermeulen (Dept. of Endocrinology and Metabolism, State Univ. of Ghent, Ghent, Belgium) and Mich Ostyn (Institute of Physical Education, Catholic Univ. of Leuven, Leuven, Belgium) for scientific advice. Yvonne Janssen, Monique Van Der Heyden, and Kerstin Mannheimer provided excellent technical assistance. Kristin Hibler (Dept. of Speech Communication, Univ. of Washington, Seattle, WA) and Dr. Gary Hibler (Portland, OR) are acknowledged for proofreading the manuscript.
FOOTNOTES
Address for reprint requests: C. De Crée, Dept. of Applied and Experimental Reproductive Endocrinology, The Institute for Gyneco-Endocrinological Research, PO Box 134, B-3000 Leuven 3, Belgium.
Received 11 February 1997; accepted in final form 16 June 1997.
REFERENCES
| 1. |
Axelrod, L.,
and
R. Tomchick.
Enzymatic O-methylation of epinephrine and other catechols.
J. Biol. Chem.
233:
702-705,
1958.
|
| 2. | Ball, P., M. Haupt, and R. Knuppen. Comparative study on the metabolism of oestradiol in the brain, the pituitary and the liver of the rat. Acta Endocrinol. 87: 1-11, 1978. |
| 3. | Ball, P., and R. Knuppen. Catecholestrogens (2- and 4-hydroxyoestrogens): chemistry, biogenesis, metabolism, occurrence and physiological significance. Acta Endocrinol. 93, Suppl. 232: S1-S128, 1980. |
| 4. |
Bergen, H.,
and
P. C. Leung.
Norepinephrine inhibition of pulsatile LH release: receptor specificity.
Am. J. Physiol.
250 ((Endocrinol. Metab. 13):
E205-E211,
1986 |
| 5. | Bullen, B. A., G. S. Skrinar, and I. Z. Beitins. Induction of menstrual cycle disorders by strenuous exercise in untrained women. N. Engl. J. Med. 312: 1349-1353, 1984. [Abstract] |
| 6. | Chiecchio, A., F. Giglioli, and R. Malvano. The imprecision profile in immunoassay. A study using a resampling technique. J. Immunol. Methods 147: 211-216, 1992[Medline]. |
| 7. | Chin, N. W., F. E. Chang, and W. G. Dodds. Acute effects of exercise on plasma catecholamines in sedentary and athletic women with normal and abnormal menses. Am. J. Obstet. Gynecol. 157: 938-944, 1987[Medline]. |
| 8. | Chou, C. P., P. M. Bentler, and A. Satorra. Scaled test statistics and robust standard errors for non-normal data in covariance structure analysis: a Monte Carlo study. Br. J. Math. Stat. Psychol. 44: 347-357, 1991. |
| 9. | De Crée, C. The possible involvement of endogenous opioid peptides and catecholestrogens in provoking menstrual irregularities in women athletes. Int. J. Sports Med. 11: 329-348, 1990[Medline]. |
| 10. |
De Crée, C.,
P. Ball,
B. Seidlitz,
K. Mannheimer,
G. Van Kranenburg,
P. Geurten,
and
H. A. Keizer.
Plasma 2-hydroxycatecholestrogen responses to acute submaximal and maximal exercise in untrained women.
J. Appl. Physiol.
82:
364-370,
1997 |
| 11. | Demers, L. M., T. S. Harrison, and D. R. Halbert. Effect of prolonged exercise on plasma prostaglandin levels. Prostaglandins 6: 413-418, 1981. |
| 12. | Drinkwater, B. L., K. Nelson, and C. H. Chesnut. Bone mineral content of amenorrheic and eumenorrheic athletes. N. Engl. J. Med. 311: 277-281, 1984[Abstract]. |
| 13. | Emons, G., P. Ball, and R. Knuppen. Radioimmunoassay of catecholestrogens. In: Catecholestrogens, edited by G. R. Merriam, and M. B. Lipsett. New York: Raven, 1983, p. 71-81. |
| 14. | Fishman, J., R. M. Boyar, and L. Hellman. Influence of bodyweight on estradiol metabolism in young women. J. Clin. Endocrinol. Metab. 41: 989-991, 1975[Abstract]. |
| 15. | Gethman, U., H. O. Hoppen, and J. Endler. Effect of catecholestrogens on prostaglandin release by rat pituitaries superfused in vitro. Arch. Gynecol. Obstet. 234: 131-135, 1983. |
| 16. | Gornbein, J. A., C. G. Lazaro, and R. J. Little. Incomplete data in repeated measures analysis. Stat. Methods Med. Res. 1: 275-295, 1992[Medline]. |
| 17. | Housh, T. J., G. O. Johnson, and D. J. Housh. Validity of skinfold estimates of percent fat in high school female gymnasts. Med. Sci. Sports Exerc. 28: 1331-1335, 1996[Medline]. |
| 18. | Kalra, S. P., and J. W. Simpkins. Evidence for noradrenergic mediation of opioid effects on luteinizing hormone secretion. Endocrinology 109: 776-782, 1981[Medline]. |
| 19. | Keizer, H. A., H. Kuipers, and J. De Haan. Effect of a 3-month endurance training program on metabolic and multiple hormonal responses to exercise. Int. J. Sports Med. 8, Suppl. 3: 150-160, 1987. |
| 20. | Keizer, H. A., P. Platen, and P. P. Menheere. The hypothalamic/pituitary axis under exercise stress: the effects of aerobic and anaerobic training. In: Hormones and Sport, edited by A. Rogol, and Z. Laron. New York: Raven, 1989, vol. 55, p. 101-105. (Serono Symposium Publ.) |
| 21. | Keizer, H. A., and A. D. Rogol. Physical exercise and menstrual cycle alterations. What are the mechanisms? Sports Med. 10: 218-235, 1990[Medline]. |
| 22. | Kelly, R. W., M. H. Abel, and R. L. Kennedy. Effects of catecholestrogens on synthesis and metabolism of prostaglandins. In: Catecholestrogens, edited by G. R. Merriam, and M. B. Lipsett. New York: Raven, 1983, p. 203-214. |
| 23. | Ladosky, W., H. C. Azambuja, and H. T. Schneider. Possible mechanism of action of 2-hydroxylated estradiol on the positive feedback control for LH release in the rat. J. Steroid Biochem. 19: 639-644, 1983[Medline]. |
| 24. | Miyabo, S., T. Nakamura, and T. Hashimoto. Effects of 2-hydroxyoestradiol and 4-hydroxyoestradiol upon prolactin and gonadotrophin secretion in women (Abstract). Acta Endocrinol. 97, Suppl. 243: 221, 1981. |
| 25. | Reznikov, A. G., and N. D. Nosenko. Catecholamines in steroid-dependent brain development. J. Steroid Biochem. Mol. Biol. 53: 349-353, 1995[Medline]. |
| 26. |
Russel, J. B.,
D. E. Mitchell,
and
P. I. Musey.
The role of -endorphin and catecholestrogens on the hypothalamic-pituitary axis in female athletes.
Fertil. Steril.
42:
690-695,
1984.
[Medline] |
| 27. |
Russel, J. B.,
D. E. Mitchell,
and
P. I. Musey.
The relationship of exercise to anovulatory cycles in female athletes: hormonal and physical characteristics.
Obstet. Gynecol.
63:
452-456,
1984.
|
| 28. | Snow, R. C., R. L. Barbieri, and R. E. Frisch. Estrogen 2-hydroxylase oxidation and menstrual function among elite oarswomen. J. Clin. Endocrinol. Metab. 69: 369-376, 1989[Abstract]. |
| 29. | Thorland, W. G., G. O. Johnson, and G. D. Tharp. Estimation of body density in adolescent athletes. Hum. Biol. 56: 439-448, 1984[Medline]. |
| 30. | Veldhuis, J. D., W. S. Evans, and L. M. Demers. Altered neuroendocrine regulation of gonadotropin secretion in women distance runners. J. Clin. Endocrinol. Metab. 61: 557-563, 1985[Abstract]. |
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R. T. Falk, T. R. Fears, X. Xu, R. N. Hoover, M. C. Pike, A. H. Wu, A. M.Y. Nomura, L. N. Kolonel, D. W. West, D. W. Sepkovic, et al. Urinary Estrogen Metabolites and Their Ratio among Asian American Women Cancer Epidemiol. Biomarkers Prev., January 1, 2005; 14(1): 221 - 226. [Abstract] [Full Text] [PDF]
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 R. K. Dubey and E. K. Jackson Genome and Hormones: Gender Differences in Physiology: Invited Review: Cardiovascular protective effects of 17{beta}-estradiol metabolites J Appl Physiol, October 1, 2001; 91(4): 1868 - 1883. [Abstract] [Full Text] [PDF]
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