Low dose of methyltestosterone in ovariectomised rats improves baroreflex sensitivity without geno‐ and cytotoxicity

This study evaluated the effects of the isolated use of a low dose of methyltestosterone (MT) on cardiovascular reflexes and hormonal levels and its geno‐ and cytotoxic safety in ovariectomized rats. Female Wistar rats were divided into four groups (n = 6), respectively: SHAM (received vehicle methylcellulose 0.5%), SHAM + MT (received MT 0.05 mg/kg), OVX (received vehicle), and OVX + MT (received MT). Twenty‐one days after ovariectomy, treatment was given orally daily for 28 days. The Bezold–Jarisch reflex (BJR) was analyzed by measuring the bradycardic and hypotensive responses elicited by phenylbiguanide (PBG) administration. The baroreflex sensitivity (BRS) was evaluated by phenylephrine and sodium nitroprussite. Myocyte hypertrophy was determined by morphometric analysis of H&E stained slides. Biochemical data were analyzed, as well as micronucleus assay. MT improved BRS and increased testosterone values, but did not change estradiol in the OVX group. MT did not promote changes in mean arterial pressure, heart rate, BJR, serum concentrations of troponin I, weight and histopathology of the heart. MT was able to restore the BRS in OVX rats. The geno‐ and cytotoxic safety of the MT was demonstrated by the absence of an increase in the micronucleus (PCEMN) or change in the ratio between normochromatic erythrocytes and polychromatic erythrocytes (NCE/PCE).     

甲基睾丸素及其它甾体的HPLC测定

以ＨＰＬＣ法测定甲基睾丸素及其它甾体，采用Ｓｈｉｍ－Ｐａｃｋ ＯＤＳ柱，甲醇－水（７２：２８）为流动相，炔诺酮为内标，检测波长为２４１或２５４ｎｍ。与ＴＬＣ、ＵＶ法相比，本法简便、准确、可靠、重现性好。     

Novel approaches to female sexual dysfunction

Female sexual dysfunction is age-related, progressive and highly prevalent, affecting 30 - 50% of American women. While there are emotional and relational elements to sexual function, it has become increasingly evident that female sexual dysfunction can occur secondary to medical problems and has an organic basis. A plethora of different female sexual dysfunctions exist and in order to obtain a greater understanding of the possible treatments for these problems, it is essential to have a strong knowledge base of female pelvic anatomy, the neurogenic mediators of female sexual response, the impact of hormones on female sexual function and the aetiologies of female sexual dysfunction. Currently, there are potential therapeutic options for the treatment of female sexual dysfunction and these options include both hormonal and pharmacological therapy. However, therapeutic agents may not prove to be enough and the ideal approach to female sexual dysfunction is thus a collaborative effort between therapists and physicians, which should include a complete medical and psychosocial evaluation, as well as inclusion of the partner or spouse in the evaluation and treatment process.     

均匀设计-效应面法优化萆薢分清直肠凝胶剂处方及其药代动力学考察

目的:采用均匀设计-效应面法优化萆薢分清直肠凝胶剂的处方,对比该复方口服和直肠给药后在家兔体内的药动学过程,为该复方的现代制剂开发提供参考。方法:以外观、均匀度、黏稠度及pH为综合考察指标,以卡波姆940用量、丙三醇与丙二醇的用量比和NaOH用量为考察因素,采用均匀设计-效应面法优化萆薢分清直肠凝胶的处方。采用HPLC检测口服和直肠给药后血浆中甘草次酸的浓度,以3P97软件计算药动学参数,评价口服和直肠给药后的体内药动学过程。结果:最优处方为1.5%卡波姆940,8%丙三醇,2%丙二醇,1%NaOH,0.03%尼泊金乙酯。直肠给药的药动学参数为药峰浓度(C_(max))(35.144 7±5.272 4)mg·L~(-1),达峰时间(T_(max))(27.114 6±13.358 7)min,药时曲线下面积(AUC_(0-6 h))(5 125.468 5±368.745 9)mg·min·L~(-1)。结论:均匀设计-效应面法适用于萆薢分清直肠凝胶剂的处方优化,建立的数学模型具有较好的预测性,所得凝胶外观细腻、黏度适宜。萆薢分清直肠凝胶剂直肠给药后主要成分在体内吸收迅速、生物利用度较高。     

促渗剂对甲睾酮透皮作用的影响

目的:考察各种促渗剂对甲睾酮喷雾剂透皮作用的影响。方法:用改良的Franz透皮扩散池,以离体鼠皮为屏障,制备包含不同种类和浓度的促渗剂的甲睾酮乙醇溶液,高效液相色谱法测定甲睾酮累积渗透量及渗透速率。结果:薄荷素油和月桂氮卓芯酮均可显著促进甲睾酮透皮吸收,其透皮效率为:月桂氮芯卓酮-薄荷油(4%~6%,v/v)>月桂氮卓芯酮-薄荷油(2%~8%,v/v)>10%薄荷素油>10%月桂氮卓芯酮>无促渗剂。结论:薄荷油和月桂氮卓芯酮体积比为6%~4%(v/v)时比使用单一促渗剂时对甲睾酮的乙醇溶液具有更佳的促渗作用。     

RP-HPLC测定甲睾酮片中甲睾酮的含量

目的建立测定甲睾酮片中甲睾酮含量的反相高效液相色谱法。方法采用Krom asil C18色谱柱,以甲醇-水(70∶30)为流动相,流速:0.8 m l/m in,检测波长:241 nm。结果甲睾酮在20.08~150.60μg/m l范围内,峰面积与其浓度线性关系良好(r=0.9997),加样回收率为100.2%。结论本法操作简便、专属性强。     

Comparative effects of oral esterified estrogens with and without methyltestosterone on endocrine profiles and dimensions of sexual function in postmenopausal women with hypoactive sexual desire

OBJECTIVE: In some women, a decline in sexual interest accompanies a relative androgen insufficiency after menopause. We sought to characterize the hormonal effects of the combination of oral esterified estrogens and methyltestosterone and to investigate whether this regimen improves hypoactive sexual desire. DESIGN: Double-blind randomized trial. SETTING: Healthy volunteers in a multicenter research environment. PATIENT(S): Postmenopausal women taking estrogen therapy who were experiencing hypoactive sexual desire. INTERVENTION(S): 4 months of treatment with 0.625 mg of esterified estrogens (n = 111) or the combination of 0.625 mg of esterified estrogens and 1.25 mg of methyltestosterone (n = 107). MAIN OUTCOME MEASURES: Baseline and end-of-study measurements of total and bioavailable testosterone and sex hormone-binding globulin (SHBG), and mean change in level of sexual interest or desire as rated on the Sexual Interest Questionnaire. RESULT(S): Treatment with the combination of esterified estrogens and methyltestosterone significantly increased the concentration of bioavailable testosterone and suppressed SHBG. Scores measuring sexual interest or desire and frequency of desire increased from baseline with combination treatment and were significantly greater than those achieved with esterified estrogens alone. Treatment with the combination was well tolerated. CONCLUSION(S): Increased circulating levels of unbound testosterone and suppression of SHBG provide a plausible hormonal explanation for the significantly improved sexual functioning in women receiving the combination of esterified estrogen and methyltestosterone.     

RP-HPLC测定甲睾酮片中甲睾酮的含量

目的建立测定甲睾酮片中甲睾酮含量的反相高效液相色谱法。方法采用Kromasil C18色谱柱，以甲醇-水（70：30）为流动相，流速：0.8ml／min，检测波长：241nm。结果甲睾酮在20．08—150．60ug／ml范围内，峰面积与其浓度线性关系良好（r=0．9997），加样回收率为100．2％。结论本法操作简便、专属性强。     

Antifertility Effects of Orally Administration of Low Dose Gossypol Acetic Acid Combined with Methyltestosterone Plus Ethinyl Estradiol on Male Rat

Objective To investigate the feasibility and optimal regimen of orally administration of low dose gossypol acetic acid （GA） combined with methyltestosterone （MT） plus ethinyl estradiol （EE） for contraception in males.
Methods Wistar male rats were randomly assigned into four groups, 20 in each group. Animals in group A or B were administered daily with 1% methyl cellulose or GA （12 mg/kg） suspended in 1% methyl cellulose, respectively. Rats in group C or D took firstly GA 12 mg/kg＋MT 20 mg/kg＋EE 0.1 mg/kg or MT 20 mg/kg＋EE 0.1 mg/kg, in a
suspension with 1% methyl cellulose, via gastric intubation. After the infertilities were initiated（6 weeks for group C, 8 weeks for group D）, GA was served alone while MT＋EE were withdrawn in rats of groups C and D. The treatment was ceased after 18 weeks and some males from group C were permitted to recover. Fertility testing, 10 males per group, was served for determining infertility or restoration of fertility in treated rats. Examinations of histology and biochemistry in treated rats were used to examine the morphologic influences on sperm, testis, epididymides and viscera, and biochemical changes in blood. The growth and development of F1 generation of the rats would also be tested in a series of behavioral tests.
Results Ten rats from group C were infertile at week 6 after treatment, and the fulfilled infertility was maintained with low-dose GA （12 mg/kg） only daily. Six weeks after cessation of treatment, all of treated males recovered their fertility. However, 8 of 10 rats from group D were in sterility at 6th week of treatment and all at 8th week of treatment, but the infertility could not be kept with the similar dose GA alone later on. Moreover, no adverse effects were found in our present experiments.
Conclusion Administration of oral low dose GA combined with MT and EE as loading dose could successfully induce infertility in short term, whereafter the efficacy could completely be maintained by similar low dose of GA alone for lon     

Increased sensitivity to phenprocoumon during methyltestosterone therapy

Summary Abnormal sensitivity to phenprocoumon in a castrated male who was receiving substitution therapy with methyltestosterone, has been studied and compared with pharmacokinetic data obtained from six control subjects, all of whom had cardiac disorders. The concentration-effect relationship for phenprocoumon in the castrated patient was evaluated by the mathematical model described by Nagashima et al. (1969). The possible mechanisms involved in sensitization by methyltestosterone of the response to phenprocoumon are discussed. It is suggested that methyltestosterone increases the affinity of the receptor sites in the liver for phenprocoumon, an effect which has previously been attributed to other C17-alkyl-substituted androgens.