| Abstrakt: |
The addition of testosterone to hormone replacement therapy (HRT) in women has beneficial effects on sexual function, being oral methyltestosterone (MT) indicated for androgen replacement in post-menopause women. There are evidences that MT improves sexual symptoms of menopause, but little is known about its safety and its cardiovascular effects used as isolated androgen therapy. We evaluate the effects of MT in ovariectomized (OVX) rats on the cardiovascular system, especially on the baroreflex sensitivity (BRS). Additionally, general, geno- and cytotoxic safety of the treatment was evaluated. Female Wistar rats were divided into 4 groups (n=6), each): control receiving vehicle (SHAM), control receiving MT (SHAM+MT), OVX receiving vehicle (OVX), and OVX receiving MT (OVX+MT), by gavage. After 21 d of castration treatment with MT (0.04 mg/day) or vehicle (methylcellulose) was performed for 28 days. The surgical procedures were executed under ketamine (100mg/Kg) and xylasine (10mg/Kg) anesthesia. The experiments were performed in accordance with the ethical principles for animal experimentation by the Brazilian College of Animal Experimentation and were approved by our Institutional Ethics, Bioethics and Animal Welfare Committee (Protocol n 118/2010). BJR was analyzed by measuring the bradycardia and hypotension responses elicited by phenyldiguanide administration (1.5-24 µg/kg). BRS was evaluated by phenylephrine (PE: 0.5-8.0µg/Kg) and nitropusside (NP: 1.0-16.0µg/Kg) randomly administration. Mean arterial pressure (MAP) and heart rate (HR) was assessed. Testosterone (T), 17β-estradiol (E2), troponin I, urea, creatinine, ALT, and AST were measured in blood samples, and geno- and cytotoxicity were evaluated by the micronucleus test. Values are expressed as the mean ± S.E.M, compared by ANOVA, followed by the post-hoc Tukey test. There was no change in MAP (SHAM: 106±2; SHAM+MT: 107±3; OVX: 106±7; OVX+MT: 107±3 mmHg), HR (SHAM: 339±13; SHAM+MT: 318±13; OVX: 340±15; OVX+MT: 337±9 bpm), and BJR sensitivity among the experimental groups. As shown in figure 1 BRS was impaired in OVX rats after MT treatment. MT treatment increase the value of T but not change E2 (SHAM 1.43±0.05, 43±3; SHAM+MT 1.38±0.03, 45±2; OVX 1.10±0.03, 15±2; OVX+MT 1.24±0.03ng/mL, 17±5pg/mL) as well as the other biochemical parameters, neither the micronucleus test (Table 1). Rats OVX+MT presented an increase in blood T, with no change in E2. These data suggest that MT as HRT improves BRS, with no lesion on kidney, liver and heart, and with geno- and cytotoxicity safety. [ABSTRACT FROM AUTHOR] |
