A comparison of transdermal and oral HRT for menopausal symptom control

BACKGROUND: To compare clinical efficacy, side effects and continuation rates using oral hormone therapy (HT), percutaneous gel, and transdermal patch. METHODS: Eighty-eight symptomatic menopausal women were allocated into 3 groups (oral, gel, patch); the patch group was further subdivided to be given either reservoir or matrix patch. After one year of follow up, symptomatic improvement, side effects and continuation rates were assessed and compared. Statistical analysis was performed using multiple analysis of variants and chi-square tests wherever appropriate, with p value < or = 0.05 considered significant. RESULTS: Percentage of patients showing complete relief from vasomotor symptoms at one year were 62%, 95%, and 100% among oral, gel, and patch groups, respectively. Similarly, above-mentioned percentages were 30%, 65%, and 68% for psychological disturbances; 64%, 100%, and 100% for genital symptoms; 40%, 90%, and 100% for urinary symptoms. Incidence of side effects, such as breakthrough bleeding [6 (60%), 6 (71%), and 5 (66%) among oral, gel, and patch groups at 6 months] and mastodynia [5 (14%), 6 (20%), and 5 (18%)] was comparable among three groups. Skin intolerance was significantly higher (92% of patients) in the reservoir patch group compared to the matrix patch (22% of patients) and gel (10% of patients) at first month. Continuation rate for one year was comparable among oral, gel, and matrix patch: 81%, 83%, and 88%, respectively. However, continuation rate was 50% among reservoir patch group. CONCLUSION: Transdermal HT performed significantly better than oral HT in menopausal symptom control. Reservoir patch was unsuitable in tropical climate where matrix patch and gel performed better.     

The prevention of CDDP-induced emesis with a combination regimen including metoclopramide, dexamethasone, droperidol and diphenhydramine

The dose limiting factors of cisplatinum are nephrotoxicity and emesis. Nephrotoxicity has been reduced by hydration but nausea and vomiting caused by cisplatinum have led to refusal of potentially curative therapy by a number of patients. The prevention of nausea and vomiting by a combination of antiemetic drugs administered to ovarian patients receiving chemotherapy inducing (cisplatinum 50mg/m2, adriamycin 300 mg/m2, cyclophosphamide 300 mg/m2 and 5FU 350 mg/m2) was studied. the combination antiemetic drugs were metoclopramide (1mg/kg), dexamethasone (10mg/m2), droperidol (1mg/m2) and diphenhydramine (20mg/body). These drugs without diphenhydramine were administered intravenously 30 minutes before and 2.5 hours, 5 hours and 7.5 hours after chemotherapy. Diphenhydramine was administered intramuscularly 30 minutes before and 5 hours after chemotherapy. No vomiting was noted in 82.6% (19/23) of cases, and no patient vomited more than four times. This combination regimen provided very good protection against cisplatinum induced emesis.     

A novel regimen of combination transdermal estrogen and intermittent vaginally administered progesterone for relief of menopausal symptoms

Objectives.?To determine the safety and efficacy of a novel regimen of transdermal estrogen and vaginally administered progesterone for treatment of menopausal symptoms.

Study Methods.?A retrospective chart review was conducted of menopausal patients aged 46–65, using an oestradiol patch and vaginally administered prometrium for at least 1 year. Available transvaginal ultrasound (TVUS) measurements of endometrial thickness and endometrial biopsy results after at least 1 year of treatment were collated. Symptom relief, bleeding and side effects were reviewed.

Results.?Forty-one patients were identified, using an estrogen patch ranging from 25 to 100?μg twice weekly and vaginal prometrium either continuously 3–5 days weekly (36 patients), or sequentially 12 days/month (5 patients). Seventeen patients were lost to follow-up or discontinued therapy within 1 year. Only 23.5% (4/17 patients) of patients who had a TVUS after 1 year (or sooner if bleeding occurred) had a thickened endometrial lining on ultrasound (>5?mm), and all of these had normal endometrial biopsies. By 1 year of follow-up, 91.7% of patients were amenorrhoeic. All patients had relief of menopausal symptoms.

Conclusions.?Vaginal administration of progesterone as part of combined estrogen plus progestin therapy has the potential for decreasing side effects while maintaining endometrial safety and amenorrhoea. Larger prospective trials are warranted.     

Prophylactic short course rectal metronidazole for cesarean section. A double-blind controlled trial of a simple low cost regimen

One hundred and eighty two patients undergoing elective and emergency cesarean section were entered in a randomized double-blind placebo controlled trial of short course metronidazole rectal suppositories. There was a significant reduction in wound infection, febrile morbidity and postoperative hospitalization in the treated group. The reduction was greatest for serious wound infection. The simplicity and low cost of the regimen make it suitable for hospitals in developing countries.     

A comparison of the antiemetic effects of droperidol and prochlorperazine in chemotherapy with cis-platinum

The antiemetic effect of droperidol was compared with that of prochlorperazine in women receiving cis-diamminedichloroplatinum. Droperidol was found to be more effective in relieving the vomiting induced by this chemotherapeutic agent. Droperidol is a butyrophenone used widely in anesthetic practice as a sedative, but the effective antiemetic dose is lower than the sedative dose.     

Continuous, combined hormone replacement: randomized comparison of transdermal and oral preparations.

OBJECTIVE: To compare two new transdermal, continuous, combined formulations and an oral regimen of hormone replacement therapy (HRT) with respect to endometrial hyperplasia, bleeding patterns, and climacteric symptoms in postmenopausal women. METHODS: This was a randomized, open, parallel-group trial during 1 year in 441 postmenopausal women who received either a 10-cm2 patch of 0.025 mg estradiol (E2) and 0.125 mg norethisterone acetate, a 20-cm2 patch of 0.05 mg E2 and 0.25 mg norethisterone acetate twice weekly, or tablets of 2 mg E2 and 1 mg norethisterone acetate once daily. The efficacy variables were frequency of endometrial hyperplasia after 1 year of treatment, number of bleeding and spotting days from the fourth to sixth treatment months, relief of climacteric symptoms, and tolerability. RESULTS: The frequency of endometrial hyperplasia was no more than 2% after 1 year of treatment in all groups. One case of simple hyperplasia was detected among the women treated with 10-cm2 patches and two among those treated with oral HRT. From the fourth to sixth treatment months, amenorrhea occurred in 73%, 47%, and 66% of the women in the 10-cm2, 20-cm2, and oral HRT groups, respectively. The 10-cm2 patches and oral treatment were associated with fewer bleeding days than were the 20-cm2 patches (P<.001). During the last 3 months of the treatment year, amenorrhea was found in 100 subjects (86%) for 10-cm2 patches, 61 (65%) for 20-cm2 patches, and in 85 (79%) for oral HRT. All treatments alleviated the climacteric symptoms to a comparable extent. CONCLUSION: In postmenopausal women, 10-cm2 patches relieved climacteric symptoms and prevented endometrial hyperplasia at least as effectively as oral HRT. Amenorrhea was induced early in a high percentage of women using 10-cm2 patches and oral HRT, and these therapies seemed to be convenient, effective, and safe for estrogen deficiency symptoms in postmenopausal women.     

Gentamicin and tobramycin in neonates: comparison of a new extended dosing interval regimen with a traditional multiple daily dosing regimen

Because of a lack of data supporting traditional dosing regimens for aminoglycosides, especially in extremely low-birth-weight infants, the authors developed revised dosing guidelines. The new guidelines increased doses to 5 mg/kg (over traditional doses of 2.5 mg/kg) and lengthened the dosing interval. When results of the two regimens were compared in 120 infants, 26.8% of infants in the traditional dosing group had subtherapeutic levels at <5 microg/mL, whereas only 1.3% of infants in the new practice dosing group were subtherapeutic. With the new dosing practice, serum levels in 1.3% of infants also exceeded the upper therapeutic range of 12 microg/mL. In conclusion, by increasing the dose of aminoglycosides and extending the dosing intervals, therapeutic levels-as defined by a C min <2 microg/mL and a C max of 5 to 12 microg/mL--were obtained significantly more often. In essence the regimen involves once daily dosing for infants <1200 g who are >30 days of age and for infants <1200 g who are >7 days of age. Serum concentrations still need to be monitored where clinically indicated.     

A randomized comparison of continuous combined transdermal delivery of estradiol-norethindrone acetate and estradiol alone for menopause. CombiPatch Study Group.

OBJECTIVE: To determine whether a continuous estradiol-norethindrone acetate transdermal delivery system reduces incidence of endometrial hyperplasia in postmenopausal women more than transdermal estradiol (E2) alone. METHODS: Six hundred twenty-five postmenopausal women were assigned randomly to one of four treatments, transdermal E2 50 microg/day, or transdermal E2-norethindrone acetate with 50 microg E2 and 140, 250, or 400 microg/day of norethindrone acetate. Follow-up visits to collect information on safety and efficacy were scheduled at 3, 6, 9, and 12 months after initiation of treatment. Endometrial biopsy for histologic evaluation was done at baseline and upon exit from the study (completion or withdrawal). Endometrial histology was evaluated by two independent gynecologic pathologists. In the event of a disparate reading, a third gynecologic pathologist evaluated the tissue using predetermined criteria. RESULTS: Endometrial hyperplasia was found in 37.9% (39 of 103) in the E2 alone group versus 0.8% (one of 123), 1% (one of 98), and 1.1% (one of 89) in the E2-norethindrone acetate 50-140, 50-250, and 50-400 groups, respectively (P < .001). Uterine bleeding was less frequent in the E2-norethindrone acetate 50-140 group than other treatments. The mean number of hot flushes per day decreased to less than one in each treatment group at endpoint. The E2-norethindrone acetate combination patch showed skin tolerance comparable to that of E2 alone. CONCLUSION: Continuous transdermal delivery of E2 combined with norethindrone acetate effectively prevented endometrial hyperplasia in healthy postmenopausal women. Continuous combined transdermal delivery systems provide increased dosing flexibility and might improve convenience and compliance with hormone replacement therapy.     

Antiemetic efficacy of high-dose corticosteroids and droperidol in cisplatin-induced emesis: A controlled trial with droperidol and metoclopramide

The nausea and vomiting associated with cisplatin chemotherapy make care of the patient more difficult for nurses and physicians, can cause severe metabolic and pathologic sequelae, and preclude further courses of chemotherapy. Current reports suggest that the two most efficacious agents for antiemetic prophylaxis are metoclopramide and corticosteroids. These two agents in combination with droperidol have been compared in a randomized controlled prospective fashion. Patients had less nausea and vomiting on the steroidal regimen than the nonsteroidal regimen (P less than 0.05), and the duration of nausea and vomiting was significantly less on the steroidal regimen (P less than 0.05). Patients expressed a preference for the steroidal regimen over the nonsteroidal one and the steroidal regimen retained its antiemetic effectiveness through repeated courses of chemotherapy. The results of the study suggest that corticosteroids and droperidol are superior antiemetic agents for cisplatin-induced nausea and vomiting.     

A randomized controlled trial of four doses of transdermal estradiol for preventing postmenopausal bone loss. Transdermal Estradiol Investigator Group.

OBJECTIVE: To determine the effects of four doses of a 7-day transdermal 17beta-estradiol (E2) delivery system, including 0.025 mg/day, on bone loss in postmenopausal women. METHODS: This was a multicenter, double-masked, randomized, placebo-controlled study of the effects of transdermal E2 at doses of 0.025, 0.05, 0.06, and 0.1 mg/day for the prevention of postmenopausal osteoporosis. Efficacy was evaluated from bone mineral density of lumbar vertebrae L2-L4, radius, proximal femur, and total hip measured with dual-energy x-ray absorptiometry. Serum osteocalcin and urinary pyridinoline and deoxypyridinoline concentrations were measured. RESULTS: At 24 months, E2 doses of 0.025, 0.05, 0.06, and 0.1 mg/day resulted in mean increases in bone mineral density of the lumbar spine of 2.37%, 4.09%, 3.28%, and 4.70%, respectively, and increased bone mineral density of the total hip by 0.26%, 2.85%, 3.05%, and 2.03%, respectively. All increases were statistically significantly greater than placebo, which decreased bone mineral density by 2.49% at the spine and 2.04% at the hip. Consistent and significant improvements in biochemical markers of bone turnover also were noted at various intervals in all treatment groups. The most frequent adverse events were local reactions from the transdermal drug-delivery system, effects of estrogen, and menopausal symptoms. CONCLUSION: Transdermal E2 at doses of 0.025, 0.05, 0.06, and 0.1 mg/day effectively prevented bone loss in postmenopausal women.     

A controlled comparison of ovarian response to controlled stimulation in first generation Asian women compared with white Caucasians undergoing in vitro fertilisation.

OBJECTIVE: To compare ovarian response to controlled stimulation among Asian women from the Indian sub-continent and white Caucasian women undergoing in vitro fertilisation (IVF). DESIGN: Nested case-control study. SETTING: Assisted Conception Unit, Birmingham Women's Hospital. SAMPLE: One hundred and eight first generation Asian patients (born in the Indian sub-continent) and 216 white Caucasian controls, all of whom received IVF treatment in the period 1994 to 1997, were selected for the study. The two groups were matched for age to within one year, early follicular phase follicle stimulating hormone, indication for treatment, gonadotrophin dose and year of treatment. The outcome of treatment was not known when the controls were selected. RESULTS: There was no statistically significant difference between the two groups in the duration of stimulation, egg number, number of embryos produced, fertilisation rate, clinical pregnancy rate, miscarriage rate, cycle cancellation rate and implantation rate. CONCLUSION: Under the same IVF protocol Asian women's response to controlled ovarian stimulation and IVF outcome are comparable to their white Caucasian peers.     

Prediction of response to controlled ovarian hyperstimulation: a comparison of basal and clomiphene citrate-stimulated follicle-stimulating hormone levels.

OBJECTIVE: To test the ovarian reserve in a high-risk population before controlled ovarian hyperstimulation for in vitro fertilization (IVF). DESIGN: A prospective study comparing the outcome of a clomiphene citrate (CC) challenge test to the outcome of subsequent IVF cycles. SETTING: Unit for assisted reproductive technology in a university hospital. PATIENTS, PARTICIPANTS: Ninety-one infertile women with an age of 35 years or more, who had previous ovarian surgery or who had been diagnosed with ovarian endometriosis. MAIN OUTCOME MEASURE: Relate follicle-stimulating hormone (FSH) levels before and after CC to frequency of cancellation of an IVF cycle because of a poor follicular response. RESULTS: Twenty-one patients had elevated basal levels of FSH. Thirty-seven patients, including 20 with high basal levels, showed an excessive FSH response to CC with an FSH level after CC above the 95% confidence limit. Clomiphene citrate-stimulated FSH levels correlated better than basal levels with response to controlled ovarian hyperstimulation. An excessive FSH response to CC predicted a poor response outcome of subsequent controlled ovarian hyperstimulation for IVF with 85% accuracy. CONCLUSION: Follicle-stimulating hormone response to CC predicts subsequent follicular response to controlled ovarian hyperstimulation.     

PEA方案与5-Fu+KSM方案治疗妊娠滋养细胞肿瘤疗效比较

目的 探讨PEA方案是否可以作为妊娠滋养细胞肿瘤联合化疗一线选择。方法 回顾性分析中国医科大学附属盛京医院2004年7月至2013年5月62例妊娠滋养细胞肿瘤患者,评价顺铂+足叶乙甙+更生霉素（PEA方案,30例）与氟尿嘧啶+更生霉素（5-Fu+KSM,32例）方案的疗效和毒副反应。结果 PEA方案治疗妊娠滋养细胞肿瘤完全缓解率为93.33%,高于5-Fu+KSM方案组（90.63%）（P>0.05）。副反应PEA组Ⅲ～Ⅳ度粒细胞减少、口腔溃疡和腹泻情况明显少于5-Fu+KSM组,差异有统计学意义（P<0.05）。PEA组恶心呕吐和肝功能损伤的发生率及严重程度均低于5-Fu+KSM组（P>0.05）。结论 两方案治疗妊娠滋养细胞肿瘤疗效相当,PEA方案副反应小、疗程短、费用少,可以作为妊娠滋养细胞肿瘤联合化疗一线选择之一。     

Prolactin secretion in Sheehan's syndrome. Responses to thyrotropin-releasing hormone and metoclopramide

The prolactin response to thyrotropin-releasing hormone (TRH) and metoclopramide was studied in 16 patients with Sheehan's syndrome and 16 matched controls in the follicular phase. Metoclopramide resulted in a greater prolactin response than TRH did in the controls. However, both stimuli failed to evoke any appreciable prolactin response in the patients with Sheehan's syndrome. Since metoclopramide is generally free of side effects and far cheaper than TRH, we recommend the prolactin response to metoclopramide as the preferred screening test in the diagnosis of Sheehan's syndrome.     

A comparison between intravaginal and oral misoprostol for labor induction: a randomized controlled trial

AIM: To compare the effectiveness and safety between intravaginal and oral misoprostol for labor induction. METHODS: One hundred and six pregnant women at term with unfavorable cervix (Bishop score < or = 4) and no contraindication to prostaglandin therapy were randomized to receive either intravaginal misoprostol 50 microg every 4 h or oral misoprostol 50 microg every 4 h for prospective randomized controlled trial study. Treatment interval from induction to vaginal delivery, maternal and neonatal complications were the main outcome measures. RESULTS: There were no statistical differences of baseline characteristics and Bishop score prior to intervention between both groups. Time interval from induction to vaginal delivery in the oral group was slightly, but significantly, longer than that of the intravaginal group (886.1 +/- 443.5 min vs 637.0 +/- 373.3 min, respectively.) Additionally, the number of doses required was significantly higher in the oral group. Nonetheless, there was no significant difference between both groups with regard to failure of induction and maternal-neonatal complications. CONCLUSION: The effectiveness in terms of failed induction and safety were comparable between intravaginal and oral misoprostol, but intravaginal route was better with respect to treatment interval and number of required doses. Both routes of administration can alternatively be used for labor induction.