Factors associated with provision of depot medroxyprogesterone acetate to adolescents by US health care providers

ObjectiveIdentify factors associated with healthcare providers' frequency of depot medroxyprogesterone acetate (DMPA) provision to adolescents.Study designWe analyzed data from surveys mailed to a nationally representative sample of public-sector providers and office-based physicians (n=1984). We estimated adjusted odds ratios (aORs) and 95% confidence intervals (CIs) of factors associated with frequent DMPA provision to adolescents in the past year.ResultsAlthough most providers (>95%) considered DMPA safe for adolescents, fewer reported frequent provision (89% of public-sector providers; 64% of office-based physicians). Among public-sector providers, factors associated with lower odds of frequent provision included working in settings without Title X funding (aOR 0.44, 95% CI 0.30–0.64), reporting primary care as their primary clinical focus versus reproductive or adolescent health (aOR 0.42, 95% CI 0.28–0.61), and providing fewer patients with family planning services. Among office-based physicians, factors associated with lower odds of frequent provision included specializing in obstetrics/gynecology (aOR 0.50, 95% CI 0.27–0.91) and family medicine (aOR 0.21, 95% CI 0.09–0.47) versus adolescent medicine, completing training ≥15 versus <5 years ago (aOR 0.27, 95% CI 0.09–0.83), and reporting that 0–24% of patients pay with Medicaid or other government healthcare assistance versus ≥50% (aOR 0.23, 95% CI 0.09–0.61). The reason most commonly reported by providers for infrequent DMPA provision was patient preference for another method.ConclusionsWhile most providers reported frequently providing DMPA to adolescents, training on evidence-based recommendations for contraception, focused on subgroups of providers with lower odds of frequent DMPA provision, may increase adolescents' access to contraception.ImplicationsAlthough >95% of providers considered depot medroxyprogesterone (DMPA) a safe contraceptive for adolescents, only 89% of public-sector providers and 64% of office-based physicians reported frequently providing DMPA to adolescents. Provider training on evidence-based recommendations for contraception counseling and provision may increase adolescents' access to DMPA and all methods of contraception.     

Effect of norethisterone acetate on serum lipid and lipoprotein parameters as well as on blood coagulation in female monkeys (M. fascicularis)

The effects of daily oral administration of a high dose of 10 mg norethisterone acetate (NET-Ac.)/kg/day over 14 weeks on serum lipid and lipoprotein parameters as well as on blood coagulation were investigated in female monkeys (M. fascicularis). Measurements of lipids and lipoprotein cholesterol were performed in weeks —5 and — 1 before treatment and in weeks 4, 8 and 12 after treatment. In addition, various blood coagulation and fibrinolytic parameters were determined in weeks 11–14 after treatment with NET-Ac. Furthermore, the serum levels of norethisterone (NET) were determined in order to monitor the real systemic compound exposure and revealed that C_max and AUC (0–3 h) values reached for norethisterone in this experiment in monkeys were about 25 times higher than those obtained after an oral contraceptive dose of NET-Ac. in women.

The results of lipid and lipoprotein cholesterol determinations showed decreases in serum total lipids, phospholipids, triglycerides and total cholesterol associated with similar decreases in HDL-, LDL- and VLDL-cholesterol fractions after NET-Ac.-treatment in monkeys. These effects were observed from week 4 onwards and maintained their magnitude up to week 12 after treatment. Since both HDL- and LDL-cholesterol fractions decreased, the HDL/LDL-ratio remained almost unchanged. Thus, the results obtained in this study after high-dose treatment with NET-Ac. in monkeys did not indicate any changes of lipid and lipoprotein parameters which in humans are supposed to be associated with an increased risk of cardiovascular lesions, namely a decrease in HDL- and increase in LDL-cholesterol fractions.

The results of blood coagulation and fibrinolytic parameters showed increased antithrombin-III and plasminogen levels besides minor changes in other parameters, thus indicating that NET-Ac. -treatment does not contribute to an increased risk of cardiovascular thrombotic events in the cynomolgus monkey.     

A variant of the HL-60 cell line expressing a high level of PTP1C exhibits increased susceptibility to differentiation by phorbol 12-myristate 13-acetate

A variant of the HL-60 cell line, HL-60/MCSFR4D2, has been found to express twice the amount of PTP1C as compared to the parental HL-60 cell line by immunoblotting and immunoprecipitation. Differentiation of the variant cells after phorbol 12-myristate 13-acetate (PMA) treatment was examined by the appearance of adherence. In 1% fetal calf serum (FCS), 20% of HL-60/MCSFR4D2 cells exhibited adherence after treatment with 0.5 ng/ml PMA for 48 h, 60% exhibited adherence after treatment with 1.0 ng/ml PMA and 80% exhibited adherence after treatment with 5.0 ng/ml PMA, while HL-60 cells exhibited only a slight response. Furthermore, antisense PTP1C oligonucleotides decreased the PMA-induced adherence of HL-60/MCSFR4D2 cells. These results suggest that the high-expression of PTP1C in HL-60 cells may be involved in the enhancement of susceptibility to macrophage-like differentiation by PMA.     

Loss of heterozygosity alterations associated with progesterone therapy in endometrial hyperplasia and adenocarcinoma

Loss of heterozygosity (LOH) was analyzed in four patients with endometrial hyperplasia (EH) with atypia (two patients) and without atypia (two patients) and in five patients with endometrial adenocarcinoma (EAC) to clarify the clinicopathologic relationship between genetic alterations and hormone therapy. Each patient was initially administered high-dose medroxyprogesterone acetate (MPA) as a uterine-sparing treatment. The five microsatellite markers used to analyze LOH were at chromosomal loci 8p22.1, 8p21, 8p21.3, 8p22, and 8p22. DNA was extracted from paraffin-embedded sections before, during, and after MPA therapy using laser capture microdissection. As a result, LOH was more frequently detected after MPA therapy (overall ratios were 16, 17, and 29% before, during, and after MPA therapy, respectively). LOH is more easily detected in EH loci than in EAC loci before MPA. For EAC, initial LOH detection on chromosome 8 may be related to an incomplete response to MPA, but negative LOH does not guarantee a favorable treatment outcome. For EH or atypical endometrial hyperplasia, it is unknown whether LOH alteration associated with MPA therapy is related to atypia of the disease.     

复方醋酸环丙孕酮和罗格列酮序贯用药对氯米芬抵抗的多囊卵巢综合征患者内分泌及生育功能的影响

目的探讨复方醋酸环丙孕酮和罗格列酮序贯用药对改善多囊卵巢综合征（PCOS）患者生育功能的临床疗效。方法30例氯米芬抵抗的PCOS胰岛素抵抗患者，口服复方醋酸环丙孕酮3个月后，罗格列酮联合氯米芬用药6个月，比较用药前后体重指数、月经周期、生殖激素水平、排卵率、妊娠率、血糖和胰岛素水平的变化。结果与用药前相比，服用复方醋酸环丙孕酮后，雄激素水平和LH／FSH值明显降低（P〈0．05），服用罗格列酮后，胰岛素抵抗指数（Homa IR）、胰岛素分泌指数（Homa β）以及β细胞功能评定指数（MBCI）均较用药前降低（P〈0．05）。结论复方醋酸环丙孕酮和罗格列酮序贯用药可有效地抑制氯米芬抵抗的PCOS患者的高雄激素血症，改善胰岛素抵抗及生育功能。     

甲地孕酮在家兔和大鼠的药物动力学

用放射免疫法(RIA)测定甲地孕酮(MA)血清浓度并计算了在家兔和大鼠静注或口服的药物动力学参数。MA口服的生物利用度,家兔为64％,大鼠为56％。MA肝微粒体酶代谢实验提示有极性较MA为大的代谢产物形成,~3H-MA十二指肠给药后30min内门静脉血中放射性远高于外周血,也有极性代谢产物形成。     

Investigation of melt agglomeration process with a hydrophobic binder in combination with sucrose stearate

The melt agglomeration process of lactose powder with hydrogenated cottonseed oil (HCO) as the hydrophobic meltable binder was investigated by studying the physicochemical properties of molten HCO modified by sucrose stearates S170, S770 and S1570. The size, size distribution, micromeritic and adhesion properties of agglomerates as well as surface tension, contact angle, viscosity and specific volume of molten HCO, with and without sucrose stearates, were examined. The viscosity, specific volume and surface tension of molten HCO were found to be modified to varying extents by sucrose stearates which are available in different HLB values and melt properties. The growth of melt agglomerates was promoted predominantly by an increase in viscosity, an increase in specific volume or a decrease in surface tension of the molten binding liquid. The agglomerate growth propensity was higher with an increase in inter-particulate binding strength, agglomerate surface wetness and extent of agglomerate consolidation which enhanced the liquid migration from agglomerate core to periphery leading to an increased surface plasticity for coalescence. The inclusion of high concentrations of completely meltable sucrose stearate S170 greatly induced the growth of agglomerates through increased specific volume and viscosity of the molten binding liquid. On the other hand, the inclusion of incompletely meltable sucrose stearates S770 and S1570 promoted the agglomeration mainly via the reduction in surface tension of the molten binding liquid with declining agglomerate growth propensity at high sucrose stearate concentrations. In addition to being an agglomeration modifier, sucrose stearate demonstrated anti-adherent property in melt agglomeration process. The properties of molten HCO and melt agglomerates were dependent on the type and concentration of sucrose stearate added.     

Ethanol regulated preference in rats

A series of experiments evaluated the determinants of preference for mixtures of ethanol plus sucrose relative to sucrose in rats. One dipper served 10% ethanol mixed with 10% sucrose, and the second dipper served 10% sucrose. Lever presses operated each dipper according to a variable-interval 5-s schedule. In three experiments the subjects were given pre-session meals of sucrose (2.5–20 ml) or sucrose (20 ml) plus chow (5 or 10 g). Pre-session meals decreased responding maintained by sucrose but not responding maintained by ethanol mixture. In two experiments body weight was varied from 85% to 125% of the initial free-feeding values. Increases in body weight, like pre-session meals, decreased responding reinforced by sucrose, but typically did not decrease responding reinforced by ethanol mixture. Throughout most of the study, ethanol consumption remained at about 1.25 ml per half hour session (3–4 g/kg per 30 min). For example, pre-session access to ethanol mixture decreased within-session ethanol consumption, but total consumption, counting both sources, remained about 1.25 ml/session. The within-session patterns of responding also differed. Responding reinforced by ethanol mix decreased as a function of ethanol consumption, whereas responding reinforced by sucrose was relatively constant throughout the session. The simplest explanation of the results is that ethanol's pharmacological consequences regulated preference.     

Naloxone administration following operant training of sucrose/water discrimination in the rat

 The suppression of food intake observed following naloxone administration has often been ascribed to palatability or taste. Unfortunately, many confounds become apparent when attempts are made to isolate such factors in the investigation of ingestive behaviors. In the present study, rats (two groups) were trained to discriminate either a 10% or 5% sucrose solution from water (0.1 ml). These mildly food deprived subjects (95% of free-feeding weight) were trained to press the appropriate lever in a two-lever operant chamber following sampling of sucrose or water; successful responding was reinforced by delivery of a 45 mg grain food pellet. Following random exposure to reduced sucrose concentrations tested under extinction, a sucrose concentration gradient (1.0, 0.5, 0.1, 0.05, 0.01 and 0.005% sucrose solution) was established for both training groups under IP saline administration. Data collected under IP saline were then compared to those collected following random IP naloxone administration (3.0, 1.0, 0.3 and 0.1 mg/kg). No significant differences were observed between the sucrose concentration gradients obtained under saline and those obtained under naloxone, suggesting that the anorectic effect of naloxone is not primarily determined by discrimination of sweet taste. Received: 4 September 1996 / Final version: 16 October 1996