Evaluation of Bazedoxifene/Conjugated Estrogens for the Treatment of Menopausal Symptoms and Effects on Metabolic Parameters and Overall Safety Profile

Abstract

Although vaginal radical trachelectomy is an effective treatment for early stage cervical cancer and has an acceptable live birth rate, there are concerns over its oncological safety and possible surgical injury with this radical procedure. Moreover, most gynecologists have difficulty performing this unfamiliar procedure and require special training. Many of these problems can be overcome with the use of abdominal radical trachelectomy. The abdominal approach provides adequate resection of the parametrial and vaginal tissue and does not require special training. Only a few case studies have investigated abdominal radical trachelectomy.This retrospective study presents follow-up data and reviews a series of cases conducted in Japanese women with early stage cervical cancer who had undergone elective abdominal radical trachelectomy and pelvic lymphadenectomy between 2002 and 2008. The aim of the study was to assess the effectiveness and safety of the abdominal approach in this population. A total of 61 patients at a median age of 33 years (range, 26-44 years) were followed up for a median 27 months (range, 1-67 months).There were 6 recurrences (9.8%, 6/61); 1 occurred in a patient with adenocarcinoma. None of the other 5 recurrences were found in cases with a primary tumor diameter of Ͻ20 mm. Twenty-nine (47.5%) of the 61 patients attempted to conceive and 4 (13.8%) were successful. Of the 4 live births, 2 were preterm, the remaining 2 were full term. The rates of serious intraoperative and postoperative complications were similar to those reported in the literature for standard radical hysterectomy and lymphadenectomy.The investigators conclude from these findings that an abdominal radical trachelectomy is an effective and relatively safe procedure in selected patients and may be an acceptable treatment option for young women with early stage cervical cancer. GYNECOLOGY Volume 65, Number 1 OBSTETRICAL AND GYNECOLOGICAL SURVEY ABSTRACTPrevious studies have demonstrated the efficacy and safety of extraperitoneal laparoscopic lymphadenectomies. The rate of peri-and postoperative complications with these procedures is below 15%. One of the most common postoperative complications, lymphocele, occurs in 3.8% to 21% of patients, and can be symptomatic or nonsymptomatic. Nonsymptomatic lymphoceles require no treatment. Although the incidence of symptomatic lymphocele has decreased with the use of systematic preventive marsupialization, this procedure does not seal the lymphatic vessels and thus does not prevent lymphatic leakage during lymph nodes dissection. A device employing ultrasonic energy, the ultrasonically activated shears (the harmonic scalpel) has been investigated for management of symptomatic lymphoceles after pelvic lymphadenectomy in patients with gynecological malignancies. This device achieves both coagulation and cutting without instrument exchanges. In a small number of studies, use of the ultrasonic shears has reduced the occurrence of lymphoceles and accomplished sealing, thereby reducing lymphatic le...

Progress and Prospects in Treating Postmenopausal Vaginal Atrophy

“…Multiple oral doses of this combination were evaluated in a multicenter, double-blind, placebo-and activecontrolled 2-year phase III trial in over 3,000 otherwise healthy, postmenopausal women. 5 In brief, bazedoxifene (20 mg)/CE (0.625 or 0.45 mg) was significantly more effective than placebo in improving vaginal atrophy and also significantly reduced the incidence of dyspareunia relative to placebo. In addition, the bazedoxifene/CE combinations were generally well tolerated and demonstrated a safety profile similar to that of placebo.…”

“…Tamoxifen and raloxifene are FDA-approved SERMs; however, neither is appropriate for systemic treatment of vaginal atrophy. Raloxifene does not have a significant positive effect on the vagina, [3][4][5] and, although tamoxifen has modest and variable estrogen-like effects on the vagina, 6-10 its long-term adverse uterine effects (e.g., endometrial cancer) would raise concerns over the risk-benefit ratio if used to treat vaginal atrophy alone. However, there are two newer SERMs in clinical development that may be candidates for the treatment of vaginal atrophy.…”

Pharmacokinetics and Safety of Bazedoxifene in Hepatically Impaired and Healthy Postmenopausal Women

“…[4][5][6] Clinically, bazedoxifene 20 mg has been shown to be safe and effective for the treatment of postmenopausal osteoporosis in women at increased risk of fracture. 7 Bazedoxifene 20 mg combined with conjugated estrogens 0.45 mg is also an established treatment for moderate to severe vasomotor symptoms (hot flashes) associated with menopause 8,9 and the prevention of postmenopausal osteoporosis. 10,11 The pharmacokinetic properties of bazedoxifene in postmenopausal women have been well characterized in previous clinical trials.…”

A Study of the Potential Interaction Between Bazedoxifene and Atorvastatin in Healthy Postmenopausal Women

“…11 Bazedoxifene, a selective estrogen receptor modulator with proestrogenic effects on lipid metabolism, 12 has been shown to be a safe and effective treatment option for osteoporosis in postmenopausal women. 13 Bazedoxifene is also part of an approved combination therapy (conjugated estrogens + bazedoxifene) that has demonstrated efficacy for the management of moderate to severe vasomotor symptoms associated with menopause 14,15 and the prevention of postmenopausal osteoporosis, 16,17 with minimal stimulation of the endometrium (at bazedoxifene doses ࣙ 20 mg) 15,17,18 or breast. 17,19,20 The pharmacokinetics of bazedoxifene have been characterized in studies in healthy postmenopausal women.…”