Treatment of premature ejaculation: New drugs and treatment strategies

This review discusses treatment options for men with premature ejaculation (PE), a common sexual dysfunction characterized by short ejaculatory latency, decreased sexual satisfaction, and distress. For a number of reasons, including embarrassment and the belief that PE is a normal part of aging, that it has no effective treatment, or that it will resolve itself, few men with PE seek treatment. Although several treatment options exist (eg, behavioral, cognitive, and sex therapy methods; desensitizing drugs; off-label use of antidepressants, phosphodiesterase type 5 inhibitors, or à-blockers), the majority of men with PE are not satisfied with their results. New pharmacologic drugs develped specifically for the treatment of PE are undergoing evaluation in clinical trials. For example, recent clinical research studies have revealed on-demand administration of one such drug, dapoxetine, which achieved significant improvements in ejaculatory latency, control over ejaculation, and satisfaction with sexual intercourse. In addition, partners of men who received dapoxetine likewise reported improved satisfaction with sexual intercourse. Future studies may reveal that integration of pharmacologic drugs with psychologic and/or behavioral therapy techniques may be the optimal approach to the management of PE. PE is a treatable condition, and new drugs in development may provide benefits over those available.     

A clinical approach to the management of a patient with suspected renovascular disease who presents with leg ischemia.

Atherosclerotic renal artery stenosis (ARAS) may cause hypertension, progressive renal failure, and recurrent pulmonary edema. It typically occurs in high risk patients with coexistent vascular disease elsewhere. Most patients with ARAS are likely to die from coronary heart disease or stroke before end-stage renal failure occurs. Recent controlled trials have shown that most patients undergoing angioplasty to treat renovascular hypertension still need antihypertensive agents 6 or 12 months after the procedure. Nevertheless, the number of antihypertensive agents required to control blood pressure adequately is lower following angioplasty than for medication alone. Trials assessing the value of revascularization for preserving renal function or preventing clinical events are only in the early recruitment phase. Revascularization should be undertaken in patients with ARAS and resistant hypertension or heart failure, and probably in those with rapidly deteriorating renal function or with an increase in plasma creatinine levels during angiotensin-converting enzyme inhibition. With or without revascularization, medical therapy using antihypertensive, hypolipidemic and antiplatelet agents is necessary in almost all cases.     

Safety and efficacy of botulinum toxin type A following long-term use

Botulinum toxin serotype A (BoNT-A) has long heritage of use leading to confidence in its safety and efficacy. The application of BoNT-A does not lead to persistent histological changes in the nerve terminal or the target muscle. Clinical trials defined the safety and tolerability profile of BoNT-A across common therapeutic indications and showed an incidence of adverse events of approximately 25% in the BoNT-A-treated group compared with 15% in the control group. Focal weakness was the only adverse event to occur more often following BoNT-A treatment. Long-term BoNT-A administration has been assessed in various treatment settings, with the level and duration of BoNT-A efficacy response being maintained over repeated rounds of injection with no major safety concerns. The treatment of children with cerebral palsy often require long-term, repeated, multimuscle BoNT-A injections that lead to the administration of comparably higher toxin doses. Despite the high total body doses used, their distribution over multiple muscles and injection sites means that systemic side effects are rare. Recent formulation changes have reduced the incidence of antibody development following treatment with BOTOX^®. These findings show long-term BoNT-A treatment to be both safe and efficacious for a wide variety of indications.     

Is atrial fibrillation an inflammatory disorder?

I read with great interest the excellent review on the influenceof inflammation in the pathogenesis of atrial fibrillation (AF)by Boos      

Matrix metalloproteinases-2 and -9 in cervical cancer: different roles in tumor progression

The incidence of uterine cervical cancer has increased slightly in Western countries, with an increase in relatively young women. Overexpression of matrix metalloproteinases (MMPs)-2 and -9 has turned out as a prognostic factor in many cancers. We compared the expression of the proteins MMP-2 and MMP-9 in cervical primary tumors with clinical outcome and risk factors of cervical cancer. One hundred sixty-one patients with cervical cancer treated in Ume? University Hospital or Sahlgrenska University Hospital, Sweden, between 1991 and 1995 were included in the study. Paraffin-embedded tissue samples obtained prior to treatment were examined immunohistochemically by specific antibodies for MMP-2 and MMP-9. Forty-two percent of the tumors were intensively positive for MMP-2 and 31% for MMP-9. Nineteen percent of the samples were intensively positive for both proteinases and 47% negative or weak for both. Overexpression of MMP-2 seemed to predict unfavorable survival under Kaplan-Meier analysis and in the multivariate analysis. Early sexual activity and low parity seemed to correlate to overexpression of MMP-2. MMP-9 was not associated with survival or sexual behavior. Intensive MMP-9 was noted in grade 1 tumors. We conclude that MMP-2 and MMP-9 have different roles in uterine cervical cancer. MMP-2 could be associated with aggressive behavior, but MMP-9 expression diminishes in high-grade tumors.     

The European Menopause Survey 2005: women's perceptions on the menopause and postmenopausal hormone therapy.

OBJECTIVES: To identify and describe current women's thoughts about the menopause, hormone treatment (HT) and perceptions about breast cancer. METHODS: Between December 2004 and January 2005, 4201 postmenopausal women in seven European countries were interviewed via a standardized computer-aided telephone interview protocol. RESULTS: Almost all women reported to have experienced climacteric symptoms, and 63% of the women rated them as being severe. Only 52% of women were aware of the benefits of HT for relief of climacteric symptoms. Although 84% felt that severe symptoms should be treated, only 40% had used HT at some point in time. Thirty-four percent of the women preferring treatment with natural products did so because of the risk of breast cancer associated with HT. HT was recognized by 59% of the women as one of the most important contributors to an increased breast cancer risk. Most women received their information about HT and breast cancer risk from the media. CONCLUSIONS: This European survey reveals that the majority of women experience climacteric symptoms but that their decision whether or not to use HT is highly dependent on their concern about breast cancer risk. An increase in knowledge of the benefits and risks of HT is required for women to make appropriate decisions about hormone use.     

Effects of estradiol alone and combined with norethisterone acetate on pulse-wave velocity in hypertensive postmenopausal women.

BACKGROUND: Arterial hypertension and postmenopausal reduction of estrogen levels may be involved in modifications of the stiffness of large arteries. OBJECTIVES: To evaluate the pulse-wave velocity (PWV) and indirectly the arterial stiffness in hypertensive postmenopausal women submitted to hormone therapy with estradiol alone or combined with norethisterone acetate. SUBJECTS: Forty-five hypertensive postmenopausal women were double-blindly, randomly assigned to three arms of treatment: placebo (group I); estradiol 2 mg/day (group II); or estradiol 2 mg/day and norethisterone acetate 1 mg/day (group III). METHODS: Arterial stiffness was assessed from PWV measurements of the common carotid and femoral arteries (CF-PWV) and the common carotid and radial arteries (CR-PWV) obtained using the automatic Complior(R) device, taken at baseline and after 12 weeks of treatment. RESULTS: After the 12-week treatment, values of CF-PWV and CR-PWV were not significantly different (p = 0.910 and p = 0.736, respectively) among the groups. Systolic blood pressure showed a positive correlation with CF-PWV in groups II and III (p = 0.02 and p < 0.001, respectively). CONCLUSIONS: PWV and arterial stiffness in postmenopausal hypertensive women did not reduce over a 12-week treatment with estradiol alone compared with the same period of treatment with estradiol combined with norethisterone acetate.