The effectiveness of the antiandrogenic agent cyproterone acetate (CA) in its contraceptive form (2 mg CA + 50 µg ethinyl estradiol) in the treatment of osteoporosis associated with athletic amenorrhea was studied in seven high-performance athletes. Four women with similar characteristics served as controls. Their mean age was 21.9 years±3.9. Training was started at a mean age of 14.0 years±2.0. The mean training intensity expressed as kilometers run per week was 35±15. Mineral density was primarily affected by the hypoestrogenic status of these athletes (= 22 pg/ml±8.8 in the midluteal phase). All participants showed low serum progesterone ( = 2.85 ng/ml±2.10) and LH profiles ( = 5.6 mlU/ml±0.8) during the midluteal phase. Cyproterone acetate was administered for 8 months to treat the increased bone loss in seven women athletes. Vertebral density appeared to be increased with 9.5%±2.45% (mean±SD) while cortical base mineral content measured at the radius was not significantly changed. Our results demonstrate that cyproterone acetate administered in combination with estrogens provides a suitable therapeutic agent in the management of osteoporosis due to a hypoestrogenic status. This treatment could substitute other contraceptive agents. Moreover, women with the most severe estrogen deficiency showed a more pronounced reaction to this therapy.

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.

Experimental studies investigating the effects of exercise on plasma total homocyst(e)ine (H[e]) levels in humans are almost non-existent. H(e) has been demonstrated to represent an independent risk factor for cardiovascular disease. The exact mechanism through which H(e) exerts its effects on the arteries is unknown but it is thought to involve nitric oxide (NO). The present study was designed to assess the effects of acute submaximal exercise on H(e) while levels of NO inhalation were manipulated using an air-filter mask. The study was completed by seven male volunteers, aged 21.6 ± 1.3 yr (X¯ ± SD), V˙O₂max: 48.6 ± 7.6 mL × kg⁻¹ × min⁻¹. During two separate occasions the subjects performed a 1-hour bout of submaximal exercise on a stationary cycle ergometer at 60 % of their V˙O₂max. The two trials were completed in random order (with and without mask). Data were collected before (PRE) and after (POST) the acute exercise bouts. Plasma H(e) was directly measured by HPLC and NO by quantifying the enzymatic oxidation to nitrite (NO₂ ⁻) & nitrate (NO₃ ⁻). Mean H(e) concentrations were 10.89 ± 2.05 nmol/mL (PRE) & 11.21 ± 1.81 nmol/mL (POST) and were not significantly altered by submaximal exercise. When wearing a mask, the correlation of the PRE/POST H(e) differences with the PRE/POST differences in NO₃ ⁻ were 0.77 (P = 0.07). No correlation was found between either H(e) and NO₂ ⁻ or between NO₂ ⁻ and NO₃ ⁻. However, a significant correlation (r = − 0.86, P = 0.03) was also observed between H(e) and NO₂ ⁻ but only for the post-exercise values when wearing a mask. The results suggest that: (1) plasma H(e) levels are not affected by acute submaximal exercise; (2) there is insufficient evidence to support the view that plasma H(e) levels are being mediated by NO during either rest or exercise. 01 Presented in part at the 46th Annual Meeting of the American College of Sports Medicine, Seattle, WA, June 2 to 5, 1999 (Session C-32).

The remarkable morphinic capacities of endogenous opioid peptides give these agents particular and interesting properties. They can be found on different locations throughout the human body, where they bind to specific receptors. By means of various agonists and antagonists it was shown that endogenous opioids possibly play a prominent role in the control of hypophyseal secretions. The menstrual cycle is thought to represent one of the most important phenomena in which these agents are involved. In the presence of a steroid-sufficient environment (that is to say, in the luteal phase) beta-endorphin exerts a tonic inhibition on the secretion of GnRH and thereby on the LH-release. Moreover, the regulation of prolactin is probably under the control of endorphins interfering via dopamine (PIF). It becomes possible to explain a number of menstrual dysfunctions in this manner. The increased plasma concentrations of beta-endorphin, which are found after physical exercise, give rise to speculations as to their involvement in the frequently appearing menstrual irregularity in women athletes. The hypothesis proposing prolactin as being entirely responsible for these phenomena is unconvincing. We believe that endogenous opioid peptides could have a possible inhibitory effect on the GnRH-LH-axis. At this moment, methodological inaccuracies and differences of various studies make it very difficult to arrive at any firm conclusion.