The role and molecular mechanism of D-aspartic acid in the release and synthesis of LH and testosterone in humans and rats.

BACKGROUND: D-aspartic acid is an amino acid present in neuroendocrine tissues of invertebrates and vertebrates, including rats and humans. Here we investigated the effect of this amino acid on the release of LH and testosterone in the serum of humans and rats. Furthermore, we investigated the role of D-aspartate in the synthesis of LH and testosterone in the pituitary and testes of rats, and the molecular mechanisms by which this amino acid triggers its action. METHODS: For humans: A group of 23 men were given a daily dose of D-aspartate (DADAVIT) for 12 days, whereas another group of 20 men were given a placebo. For rats: A group of 10 rats drank a solution of either 20 mM D-aspartate or a placebo for 12 days. Then LH and testosterone accumulation was determined in the serum and D-aspartate accumulation in tissues. The effects of D-aspartate on the synthesis of LH and testosterone were gauged on isolated rat pituitary and Leydig cells. Tissues were incubated with D-aspartate, and then the concentration (synthesis) of LH and cGMP in the pituitary and of testosterone and cAMP in the Leydig cells was determined. RESULTS: In humans and rats, sodium D-aspartate induces an enhancement of LH and testosterone release. In the rat pituitary, sodium D-aspartate increases the release and synthesis of LH through the involvement of cGMP as a second messenger, whereas in rat testis Leydig cells, it increases the synthesis and release of testosterone and cAMP is implicated as second messenger. In the pituitary and in testes D-Asp is synthesized by a D-aspartate racemase which convert L-Asp into D-Asp. The pituitary and testes possesses a high capacity to trapping circulating D-Asp from hexogen or endogen sources. CONCLUSION: D-aspartic acid is a physiological amino acid occurring principally in the pituitary gland and testes and has a role in the regulation of the release and synthesis of LH and testosterone in humans and rats.

Satisfaction and compliance in hormonal contraception: the result of a multicentre clinical study on women's experience with the ethinylestradiol/norelgestromin contraceptive patch in Italy.

BACKGROUND: For many women finding the right contraceptive method can be challenging and consistent and correct use over a lifetime is difficult. Even remembering to take a birth control pill every day can be a challenge. The primary objective of this study was to evaluate women's experience with a weekly ethinylestradiol/norelgestromin contraceptive patch (EE/NGMN patch), given new technologies recently developed in hormonal contraception to increase women's options in avoiding daily dosing. METHODS: In 24 Italian sites, 207 women received the EE/NGMN patch for up to 6 cycles. At study end, overall satisfaction and preference, as well as compliance, efficacy and safety, were evaluated. RESULTS: 175 women (84.5%) completed the study. The overall satisfaction rate was 88%; convenience and once-a-week frequency of the patch were especially appreciated. At baseline, 82 women (39.4%) were using a contraceptive method, mainly oral contraceptives and barrier methods, but only 45.1% were very satisfied/satisfied; after 6 months with the patch, 86.3% of this subset was very satisfied/satisfied. Considering the method used in the 3 months before the study entry, 78.1% strongly preferred/preferred the patch, for convenience (53.9%), ease of use/simplicity (28.9%), fewer (9.2%) and less severe (2.6%) side effects. Compliance was very high: 1034/1110 cycles (93.2%) were completed with perfect compliance and the mean subject's compliance score was 90%. One on-therapy pregnancy occurred. The patch was safe and well tolerated: adverse events frequency was low, with predominantly single reports of each event. Most of them started and subsided during cycle 1. CONCLUSION: This study demonstrated that the EE/NGMN patch is associated with high satisfaction levels and excellent compliance. At study end, the majority of women indicated that they would continue using the patch.

Effect of the ethinylestradiol/norelgestromin contraceptive patch on body composition. Results of bioelectrical impedance analysis in a population of Italian women.

BACKGROUND: As weight gain is one of the most frequently cited reasons for not using and for discontinuing hormonal contraceptives, in an open-label, single-arm, multicentre clinical study we evaluated the effect of the ethinylestradiol/norelgestromin contraceptive patch (EVRA, Janssen-Cilag International, Belgium) on body composition using bioelectrical impedance analysis (BIA). METHODS: Body weight and impedance vector components (resistance (R) and reactance (Xc), at 50 kHz frequency, Akern-RJL Systems analyzer) were recorded before entry, after 1, 3 and 6 months in 182 Italian healthy women aged 29 yr (18 to 45), and with BMI 21.8 kg/m2 (16 to 31). Total body water (TBW) was estimated with a BIA regression equation. Vector BIA was performed with the RXc mean graph method and the Hotelling's T2 test for paired and unpaired data. RESULTS: After 6 months body weight increased by 0.64 kg (1.1%) and TBW increased by 0.51 L (1.7%). The pattern of impedance vector displacement indicated a small increase in soft tissue hydration (interstitial gel fluid). Body composition changes did not significantly differ among groups of previous contraceptive methods. Arterial blood pressure did not significantly change over time. CONCLUSION: After 6 months of treatment with the ethinylestradiol/norelgestromin contraceptive patch we found a minimal, clinically not relevant, increase in body weight less than 1 kg that could be attributed to an adaptive interstitial gel hydration. This fluctuation is physiological as confirmed by the lack of any effect on blood pressure. This could be useful in increasing women's choice, acceptability and compliance of the ethinylestradiol/norelgestromin contraceptive patch.

Occurrence of D-aspartic acid in human seminal plasma and spermatozoa: possible role in reproduction.

OBJECTIVE: To determine D-aspartic acid (D-Asp) in human seminal plasma and spermatozoa in fertile and infertile donors. DESIGN: Prospective observation study. SETTING: Department of Pathophysiology for Human Reproduction, Hospital "S. Luca," Salerno, Italy, and Department of Neurobiology and Comparative Physiology, Zoological Station "A. Dohrn," Naples, Italy. PATIENT(S): Ten normospermic, 10 oligoasthenoteratospermic, and 10 azoospermic (nonobstructive) men. INTERVENTION(S): D-aspartic acid was determined by a specific enzymatic high-performance liquid chromatography method on purified seminal plasma and on isolated spermatozoa and by an immunohistochemical method using light and electronic microscopic techniques. MAIN OUTCOME MEASURE(S): Concentration of D-Asp in seminal plasma and in isolated spermatozoa; subcellular localization of D-Asp in the acrosome and nucleus. RESULT(S): The concentration of D-Asp in seminal plasma and in spermatozoa was significantly reduced in oligoasthenoteratospermic donors. In the seminal fluid of normospermic donors, D-Asp occurs at a concentration of 80 +/- 12 nmol/mL semen (10.4 +/- 1.5 microg/mL), whereas 26 +/- 6 nmol/mL semen were found in oligoasthenoteratospermic donors, and 12 +/- 1.5 nmol/mL semen were found in azoospermic donors. In spermatozoa from normospermic donors, D-Asp occurred at a concentration of 130 +/-15 fmol per spermatozoa (17.0 +/- 1.96 ng per spermatozoa), vs. 60.5 +/- 5.0 fmol per spermatozoa from oligoasthenoteratospermic subjects. Other D-amino acids analyzed were not present in seminal plasma or in spermatozoa in a significant concentration compared with D-Asp. CONCLUSION(S): D-aspartic acid occurs in human seminal plasma and spermatozoa and is implicated in male fertility.