A 1-year pharmacokinetic investigation of a novel oral contraceptive containing drospirenone in healthy female volunteers.

Drospirenone is a novel synthetic progestogen with a pharmacological profile similar to that of natural progesterone. It has been developed in combination with ethinylestradiol for use as an oral contraceptive (EE/DRSP, Yasmin, Schering AG, Berlin, Germany). The pharmacokinetic characteristics of drospirenone and ethinylestradiol have been assessed in healthy female volunteers over a 1-year period. During each of the 13 treatment cycles, volunteers received the combined active ingredients for 21 days, followed by a 7-day, tablet-free interval. The concentrations of the serum proteins, sex hormone binding globulin (SHBG) and corticoid binding globulin (CBG), were determined at intervals after the cessation of treatment (day 21) at the end of cycles 1, 6, 9 and 13. Drospirenone and ethinylestradiol were found to be absorbed rapidly and to reach a peak concentration in serum 1.5-2.0 h after dosing. Serum concentrations ofdrospirenone declined, with mean terminal half-lives of 30.8-32.5 h. Accumulation of both drospirenone and ethinylestradiol was observed within a treatment cycle, with a mean accumulation ratio of 3.0 for drospirenone and 2.1 for ethinylestradiol. In addition, serum drospirenone concentrations increased between treatment cycles 1 and 6, but remained steady thereafter, as reflected in the AUC values determined at the end of treatment cycles 1, 6, 9 and 13. Serum SHBG and CBG concentrations declined in a biphasic manner after cessation of treatment at the end of cycle 13, and physiological steady-state concentrations were reached within 4-6 weeks. In conclusion, drospirenone was absorbed at a similar rate as other synthetic progestogens contained in various oral contraceptives, as indicated by similar tmax values. The terminal half-life of drospirenone was intermediate between those of 19-nortestosterone derivatives like desogestrel, levonorgestrel or gestodene and C21-progestogens like cyproterone acetate. Both active ingredients of the new contraceptive EE/DRSP showed accumulation within a treatment cycle, which is also the case with other synthetic progestogen/ethinylestradiol combinations. Similar to other oral contraceptives, a reversible induction of serum SHBG and CBG concentrations was observed under EE/DRSP treatment.     

A 1-year pharmacokinetic investigation of a novel oral contraceptive containing drospirenone in healthy female volunteers

Drospirenone is a novel synthetic progestogen with a pharmacological profile similar to that of natural progesterone. It has been developed in combination with ethinylestradiol for use as an oral contraceptive (EE/DRSP, Yasmin®, Schering AG, Berlin, Germany). The pharmacokinetic characteristics of drospirenone and ethinylestradiol have been assessed in healthy female volunteers over a 1-year period. During each of the 13 treatment cycles, volunteers received the combined active ingredients for 21 days, followed by a 7-day, tablet-free interval. The concentrations of the serum proteins, sex hormone binding globulin (SHBG) and corticoid binding globulin (CBG), were determined at intervals after the cessation of treatment (day 21) at the end of cycles 1, 6, 9 and 13. Drospirenone and ethinylestradiol were found to be absorbed rapidly and to reach a peak concentration in serum 1.5–2.0 h after dosing. Serum concentrations of drospirenone declined, with mean terminal half-lives of 30.8–32.5 h. Accumulation of both drospirenone and ethinylestradiol was observed within a treatment cycle, with a mean accumulation ratio of 3.0 for drospirenone and 2.1 for ethinylestradiol. In addition, serum drospirenone concentrations increased between treatment cycles 1 and 6, but remained steady thereafter, as reflected in the AUC values determined at the end of treatment cycles 1, 6, 9 and 13. Serum SHBG and CBG concentrations declined in a biphasic manner after cessation of treatment at the end of cycle 13, and physiological steady-state concentrations were reached within 4–6 weeks.

In conclusion, drospirenone was absorbed at a similar rate as other synthetic progestogens contained in various oral contraceptives, as indicated by similar t_max values. The terminal half-life of drospirenone was intermediate between those of 19-nortestosterone derivatives like desogestrel, levonorgestrel or gestodene and C21-progestogens like cyproterone acetate. Both active ingredients of the new contraceptive EE/DRSP showed accumulation within a treatment cycle, which is also the case with other synthetic progestogen/ethinylestradiol combinations. Similar to other oral contraceptives, a reversible induction of serum SHBG and CBG concentrations was observed under EE/DRSP treatment.     

A randomized, controlled trial of a low-dose contraceptive containing 20 microg of ethinyl estradiol and 100 microg of levonorgestrel for acne treatment

OBJECTIVE: To evaluate the efficacy of a low-dose oral contraceptive (OC) containing 100 microg of levonorgestrel (LNG) and 20 microg of ethinyl estradiol (EE) compared with placebo for the treatment of moderate acne. DESIGN: Multicenter, randomized, double-blind, placebo-controlled clinical trial. SETTING: Outpatient dermatology clinics. PATIENT(S): Women (> or =14 years old; n = 350) with normal menstrual cycles and moderate acne were randomized to receive LNG/EE or placebo for six cycles.Intervention(s): Twenty microg of EE and 100 microg of LNG. MAIN OUTCOME MEASURE(S): Acne lesion counts and clinician global assessment were performed at baseline and at each cycle. Patient self-assessment was carried out at baseline and at cycles 4 and 6; blood pressure and weight were measured at baseline and at cycles 1, 3, and 6. RESULT(S): Inflammatory, noninflammatory, and total lesion counts at cycle 6 with LNG/EE were significantly lower compared to placebo. Patients in the LNG/EE group also had significantly better clinician global and patient self-assessment scores than those in the placebo group at cycle. Changes in weight from baseline were similar between patients in the LNG/EE and placebo groups at all measured time points. CONCLUSION(S): This double-blind, placebo-controlled study demonstrates that a low-dose OC containing 20 microg of EE and 100 microg of LNG is an effective and safe treatment for moderate acne.     

The effect of intrauterine and oral levonorgestrel administration on serum concentrations of sex hormone-binding globulin, insulin and insulin-like growth factor binding protein-1.

BACKGROUND: The concentrations of sex hormone-binding globulin (SHBG) have been shown to decrease during the use of levonorgestrel (LNG)-containing contraception. This decrease has been thought to be due to the androgenic action of LNG. In endogenously hyperandrogenic women, particularly in those with increased body weight, serum SHBG correlates with circulating insulin-like growth factor binding protein-1 (IGFBP-1) concentration, and both are inversely related to insulin. LNG-containing combined contraceptives have also been reported to increase the pancreatic insulin secretion. OBJECTIVE: To examine whether serum insulin and IGFBP-1 levels are related to SHBG during the use of intrauterine or oral levonorgestrel contraception. METHODS: Thirty-one fertile women were divided into three study groups: A copper-releasing intrauterine device (IUD) was inserted in control group (n= 10), and the LNG-releasing intrauterine contraceptive system (LNG-IUS) in group II (n= 10), and 30 mirog LNG-containing contraceptive minipills were given in group III (n=11). Twenty-nine women completed the study and one woman was excluded because of a high body mass index. Fasting concentrations of blood glucose, insulin, SHBG, IGFBP-1, testosterone and LNG before and after three-months-use of contraception were measured. RESULTS: SHBG concentrations decreased slightly during oral LNG contraception, but not during the use of the LNG-IUS. No change was found in blood glucose, serum insulin, serum IGFBP-1 and serum total testosterone concentrations in either group. In our study group, including women with normal body weight, no correlation was detected between insulin and SHBG concentrations before or after LNG contraception, whereas an inverse correlation was found between insulin and IGFBP-1 levels at the baseline as well as after LNG-IUS use (R2= 0.578; p=0.001). Multiple regression analysis showed no significant association between the levels of SHBG and IGFBP-1 as dependent factors, and glucose, insulin, LNG, age, waist-hip ratio and body mass index as dependent factors. CONCLUSIONS: Our data imply that the effect of levonorgestrel on variables associated with endogenous hyperandrogenism remains borderline in women with normal body mass index.     

Comparison of two oral contraceptives containing either drospirenone or cyproterone acetate in the treatment of hirsutism.

Combined oral contraceptives (COCs) are considered the first-line treatment for women with hirsutism. They diminish androgen release from the ovary and decrease plasma free testosterone levels by increasing sex hormone-binding globulin (SHBG) concentrations. COCs containing cyproterone acetate (CPA) and drospirenone (DRSP) have been proved effective for the treatment of acne and facial hirsutism. This study prospectively compared the clinical and biochemical efficacy of 3 mg DRSP/30 microg ethinyl estradiol (EE) and 2 mg CPA/35 microg EE combinations in a total of 91 patients with hirsutism. Individuals randomly received a cyclic combination of either DRSP/EE (n=48) or CPA/EE (n=43) for 12 months. Basal serum total testosterone, free testosterone, androstenedione, dehydroepiandrosterone sulfate and SHBG levels, as well as Ferriman-Gallwey scores, were determined before and after treatment. Both COCs achieved a similar effect on clinical hirsutism scores, in addition to serum androgen and SHBG levels, after completion of therapy. The percentage reductions in total hirsutism score (median % (min-max)) during therapy were 0.70 (0-0.58) vs. 0.57 (0.10-1.00) at 6 months (p = 0.028) and 0.80 (0-0.42) vs. 0.81 (0-0.75) at 12 months (p = 0.6) in the DRSP/EE and CPA/EE groups, respectively. In conclusion, the DRSP/EE combination is at least as effective as the CPA/EE combination in improving hirsutism scores.     

Single and multiple administration of a new triphasic oral contraceptive to women: pharmacokinetics of ethinyl estradiol and free and total testosterone levels in serum

Ethinyl estradiol is part of almost every combined oral contraceptive, and its pharmacokinetic characteristics have been thoroughly investigated in numerous studies. However, little is known about its pharmacokinetics during long-term administration, as compared with single-dose administration. In this study 10 women received a triphasic formulation that contained ethinyl estradiol together with the progestin gestodene over one treatment cycle. Mean area under the curve values of ethinyl estradiol were significantly higher on the last treatment day, as compared with the corresponding values obtained from the same women after single-dose administration. However, the observed increase in area under the curve was within the range of pharmacokinetic accumulation, to be expected on the basis of dosing interval and terminal half-life. Another point of interest was the effect of the triphasic preparation on testosterone concentrations in serum. Both total and free testosterone levels were suppressed by about 60% as compared with pretreatment values, and there was no correlation with corresponding sex hormone-binding globulin levels in the serum.     

Effects of a monophasic combined oral contraceptive containing nomegestrol acetate and 17β-oestradiol in comparison to one containing levonorgestrel and ethinylestradiol on markers of endocrine function

ABSTRACT

Objectives To compare the effects of two monophasic combined oral contraceptives, containing either nomegestrol acetate/17β-oestradiol (NOMAC/E2) or levonorgestrel/ ethinylestradiol (LNG/EE) on endocrine function, androgens, and sex hormone-binding globulin (SHBG).

Methods Randomised, open-label, multi-centre trial involving 121 healthy women, aged 18–50 years old. Participants received NOMAC/E2 (2.5 mg/1.5 mg) in a 24/4-day regimen (n = 60) or LNG/EE (150 μg/30 μg) in a 21/7-day regimen (n = 61) for six cycles. The primary outcome was the change from baseline to cycle 6 in markers of adrenal and thyroid function, androgens, and SHBG.

Results Total cortisol, corticosteroid-binding globulin (CBG), and thyroxine-binding globulin (TBG) increased from baseline in both groups, with significantly greater increases in the LNG/EE group. No relevant changes from baseline or differences between the groups were observed for thyroid-stimulating hormone (TSH) and free thyroxine (T₄). Androgens and androgen precursors decreased from baseline in both groups, with significantly greater decreases in the LNG/EE group (except for free testosterone). A greater increase in SHBG was observed with NOMAC/E2 than with LNG/EE.

Conclusions NOMAC/E2 has significantly less influence on markers of adrenal and thyroid function and androgens than LNG/EE. The clinical relevance of these findings requires further study.     

Transfer of drospirenone to breast milk after a single oral administration of 3 mg drospirenone + 30 microg ethinylestradiol to healthy lactating women.

Drospirenone (DRSP) is a synthetic progestogen which has been developed in combination with ethinylestradiol (EE) for use as an oral contraceptive (Yasmin, Schering AG, Berlin, Germany). The pharmacokinetic characteristics of DRSP were evaluated in serum and breast milk from lactating women who received a single oral dose of 3 mg DRSP + 30 microg EE, to determine the fraction of the dose of DRSP which transfers to breast milk. Nine healthy, lactating women were included into the present study and pharmacokinetic data were obtained from six participants. The maximum DRSP concentrations (data given as mean +/- standard deviation) were reached on average 2.5+/-1.2 and 2.8+/-1.3 h in serum and breast milk, respectively after oral administration of 3 mg DRSP + 30 microg EE, and amounted on average to 30.8+/-14.4 and 13.5+/-11.7 ng DRSP/ml in serum and breast milk. The mean breast milk versus serum concentration ratios of DRSP increased from 0.16 to 0.57 within 2 h after dosing and decreased to 0.16 after 24 h. The average ratio of AUC0-48 h, values in breast milk versus serum was 0.23+/-0.09. The mean DRSP concentration in breast milk over the 24-h period after dosing was 3.7+/-1.9 ng/ml. The amount of DRSP measured to be transferred into breast milk in the six women participating in the present study was, on average, 635 ng (range 256.2-1357.9 ng) within 24 h, corresponding to about 0.02% of the maternal dose. Based on the average concentration of the drug in breast milk over 24 h and assuming a daily ingestion of approximately 800 ml breast milk, the daily dose that reaches an infant via breast milk is estimated to be approximately 3 microg DRSP. The subjective and objective tolerances of 3 mg DRSP + 30 microg EE were good, with no adverse events reported.     

A randomized controlled trial of second- versus third-generation oral contraceptives in the treatment of acne vulgaris

OBJECTIVE: This study was undertaken to compare the clinical efficacy of second- versus third-generation oral contraceptives in the treatment of acne. STUDY DESIGN: Thirty-four women with acne were randomly selected to receive an oral contraceptive containing 0.3 mg of ethinyl estradiol (EE)/0.15 mg of desogestrel or 0.3 mg of EE/0.15 mg of levonorgestrel for 9 months. Acne was scored by lesion counting by a single examiner, and serum was analyzed for sex hormone-binding globulin (SHBG), dehydroepiandrosterone sulfate (DHEAS), and free and total testosterone at baseline and 3-month intervals. RESULTS: At baseline, the two treatment groups did not differ in the mean age, body mass index, acne lesion counts, SHBG, DHEAS, or free and total testosterone. Mean acne lesion counts decreased significantly in both groups from baseline (P <.02). In subjects completing 9 months of therapy, acne decreased by 52.8% in the EE/levonorgestrel group (n = 9) and by 58.5% in the EE/desogestrel group (n = 7) (between groups: P not significant). Mean SHBG increased by 46.3 nmol/L in the EE/desogestrel group (P not significant), and 20.0 nmol/L in the EE/levonorgestrel group (P <.05). Decreases in free testosterone from baseline occurred in each group, but these differences did not reach statistical significance. CONCLUSION: Oral contraceptives containing EE/desogestrel and EE/levonorgestrel were both effective in treating acne.     

Sex hormone--binding globulin--a surrogate marker for the prothrombotic effects of combined oral contraceptives

OBJECTIVE: The purpose of this study was to investigate the plausibility of serum sex hormone-binding globulin (SHBG) concentration as a risk marker for venous thromboembolism (VTE) during use of combined oral contraceptives (COC).Study design This was a prospective, randomized cross-over study. Thirty-five women were treated with COCs containing the same amount of ethinyl estradiol and either levonorgestrel (LNG/EE) or desogestrel (DG/EE). Serum SHBG and markers of hemostasis were determined before and after 2 months on each treatment. RESULTS: SHBG increased significantly with both preparations. Treatment with DG/EE caused more pronounced prothrombotic changes in hemostatic parameters than LNG/EE. With both treatment regimens, there was a significant correlation between changes in resistance to activated protein C (APCr) and changes in plasma SHBG. CONCLUSION: The correlation between SHBG and the well-established risk factor APCr might indicate the usefulness of SHBG as a risk marker for VTE during COC treatment.     

新型左炔诺孕酮/炔雌醇复方避孕贴剂的家兔药代动力学研究

目的:探讨新型左炔诺孕酮(levonorgestrel,LNG)和炔雌醇(ethynylestradiol,EE)在家兔体内的药物动力学特征,评价多次给药后是否出现药物蓄积情况。方法:家兔在单次和多次给药及停止给药后不同时间点耳缘静脉采血,选择放射免疫分析(radioimmunoassay,RIA)法测定各时间点各组家兔雌/孕激素的血药浓度,使用药物动力学软件计算各药物动力学参数并对其进行统计分析。结果:单次给药后受试贴剂低(10cm2)、中(20 cm2)和高剂量(40 cm2)组血清LNG峰浓度(Cmax)分别为1.04±0.12 ng/ml、2.42±0.60 ng/ml和4.90±1.39 ng/ml,3组间有显著差异(P<0.05)。血药浓度-时间曲线下面积(AUC)分别为49.93±9.79h.ng/ml、115.14±34.25 h.ng/ml和251.22±80.55 h.ng/ml,3组间有显著差异(P<0.01);血清EE峰浓度(Cmax)分别为112.00±45.50 pg/ml、139.23±28.23 pg/ml和290.26±66.62 pg/ml,中、高剂量组间有显著差异(P<0.05),而中、低剂量组间无统计学差异(P>0.05)。EE血药浓度-时间曲线下面积(AUC)分别为4.70±1.34 h.ng/ml、6.59±1.23h.ng/ml和16.59±2.33 h.ng/ml,中、高剂量组之间有显著差异(P<0.01)。Evra参比避孕贴剂组血清LNG浓度的Cmax为3.16±1.00 ng/ml,AUC为155.29±46.14 h.ng/ml,与LNG/EE避孕贴剂中剂量组(拟采用的临床试验剂量)相比,两者无显著差异(P>0.05)。中剂量组血清EE浓度与Evra避孕贴剂的相比显著降低(P<0.05)。多次给药后LNG/EE避孕贴剂10 cm2组和20 cm2组在重复给药10次的过程中未出现LNG和EE血药浓度蓄积现象,Evra贴剂组在重复给药4次的过程中未出现LNG和EE血药浓度蓄积现象。结论:中剂量的LNG/EE避孕贴剂具有良好的避孕效果,同时其副作用可能小于Evra。     

Body weight change during use of a monophasic oral contraceptive containing 20 microg ethinylestradiol and 75 microg gestodene with a comparison of the women who completed versus those who prematurely discontinued intake.

OBJECTIVES: Evaluation of the impact of an oral contraceptive on body weight with a comparison ofwomen who completed versus women who prematurely discontinued intake. METHODS: Data on body weight were retrospectively analyzed from four large prospective clinical trials with an oral contraceptive containing 20 microg ethinylestradiol and 75 microg gestodene (EE/GSD). A total of 1971 young fertile women were included in the evaluation, and 1467 completed 12 cycles. RESULTS: We found no clinically relevant change of body weight during treatment with an oral contraceptive containing 20 microg ethinylestradiol and 75 microg gestodene in the vast majority of users after 12 treatment cycles. The mean change of body weight was less than 0.3 kg in this time period for all users. Nearly 70% of women experienced a minor change in their body weight of +/- 2 kg. An additional 13% lost more than 2 kg body weight in the course of 12 treatment cycles. A total of 11% increased their weight by 2-4 kg. A total of 1255 (85.5%) of women had a body mass index (BMI) of < or = 25 at baseline compared to 1253 (85.4%) after 12 cycles of treatment. There was no significant difference in the change ofbody weight between the women completing 12 cycles of treatment and those who prematurely discontinued EE/GSD. CONCLUSIONS: This retrospective analysis confirms that there was only a negligible change of body weight during intake of an oral contraceptive containing 20 microg ethinylestradiol and 75 microg gestodene. There was no difference in weight change between the women completing the study or discontinuing intake.     

左旋18-甲基炔诺酮经阴道给药的药代动力学和药效学研究

本文比较了左旋18-甲基炔诺酮(LNG)制剂Postinor单剂量(0.75mg)口服和阴道给药的药代动力学,并研究了这种制剂经阴道多次给药的药代动力学及对卵巢功能的影响。征集6例月经规则的健康育龄妇女。第一周期,每例对象每次于阴道深处放置一片Postinor,共8次,每2次间隔为48小时;第二周期,每例对象口服一片相同的LNG制剂,放免测定血清LNG、雌二醇和孕酮水平。结果表明在第一周期,除1例对象在中期有一较高的雌二醇峰以外,其余雌、孕激素水平均呈明显低平状态;口服和阴道放置相同的单剂量LNG以后血清LNG浓度时间曲线分别符合二室与一室开放模型。由此提示与口服相比,Postinor经阴道给药后吸收缓慢,且血清LNG峰值低,而消除过程则两种给药途径较为相似;Postinor经阴道给药可明显抑制排卵。     

Effect of low-dose oral contraceptive on gonadotropins, androgens, and sex hormone binding globulin in nonhirsute women

The effectiveness of a low-dose oral contraceptive (OC) in suppressing plasma levels of gonadotropins, ovarian, and adrenal androgens and stimulating sex hormone-binding globulin (SHBG) was evaluated prospectively in nonhirsute women. Thirty-three women ingested 35 micrograms of ethinyl estradiol and 1 mg of norethindrone beginning within day 1 to 5 of the menstrual cycle. Baseline levels of luteinizing hormone, follicle-stimulating hormone, total testosterone (T), androstenedione (A), dehydroepiandrosterone sulfate (DHEAS), and SHBG were obtained before ingestion of the OC and repeated after 3, 6 and, 9 months of OC use on day 1 to 5 of the OC "cycle". A significant suppression of gonadotropin levels is seen in nonhirsute women. Sex hormone binding globulin is consistently stimulated by the low-dose OC. A significant suppression of T and DHEAS is observed. No change was seen in levels of A. The demonstrated effects become evident at 3 months and are maintained at 6 and 9 months.     

Levels of sex hormone-binding globulin and corticosteroid-binding globulin mRNAs in corpus luteum of human subjects: correlation with serum steroid hormone levels.

To understand regulation of the function of human ovarian corpus luteum by sex steroid-binding proteins, the levels of luteal intracellular sex hormone-binding globulin (SHBG) and corticosteroid-binding globulin (CBG) mRNAs and serum steroid hormones were simultaneously determined. The expression of SHBG and CBG mRNAs was detected in all samples analyzed. SHBG mRNA level was positively correlated with serum estradiol-17 beta level (p < 0.05), but not with serum progesterone level. There was a positive correlation between SHBG mRNA level and serum estradiol-17 beta/progesterone ratio (p < 0.01). On the other hand, CBG mRNA level was positively correlated with serum estradiol-17 beta and progesterone level (p < 0.01 and p < 0.01, respectively). There was no correlation between CBG mRNA level and serum estradiol-17 beta/progesterone ratio. SHBG and CBG mRNA levels were not correlated with the levels of serum testosterone, free testosterone or cortisol. These findings suggest that the synthesis of luteal SHBG and CBG is complexly regulated by estrogen and progesterone, and that SHBG and CBG interact with estrogen and progesterone, respectively, for luteal steroidal activity.     

Efficacy of an oral contraceptive containing drospirenone in the treatment of women with polycystic ovary syndrome.

OBJECTIVE: To investigate the efficacy of a combined oral contraceptive containing 30 microg ethinyloestradiol and 3 mg drospirenone in the treatment of hyperandrogenism affecting women with the polycystic ovary syndrome (PCOS). METHODS: Prospective open study of 20 women for six cycles. At the beginning and at the end of the study the following values were determined: the Ferriman-Gallwey (F-G) score, body mass index, waist/hip ratio, serum levels of testosterone, SHBG, immune reactive insulin (IRI), glucose, the free androgenic index, and insulin resistance (HOMA-IR). RESULTS: All 20 women completed six cycles of therapy. The medication was well tolerated. At the end of the study there was a significant improvement of hirsutism, expressed in the decrease of the F-G score, accompanied by a decrease of testosterone and an increase of SHBG values. The carbohydrate metabolism was not affected significantly. CONCLUSION: The combined oral contraceptive containing 30 microg ethinyloestradiol and 3 mg drospirenone is an effective drug in the treatment of hyperandrogenism in women with PCOS; it elicits few side effects and does not significantly influence insulin resistance.     

Use of the novel combined contraceptive vaginal ring NuvaRing for ovulation inhibition

OBJECTIVE: To assess the effects of the combined contraceptive vaginal ring NuvaRing on ovarian function. DESIGN: Randomized, open-label, crossover study. SETTING: Clinical pharmacology unit. PARTICIPANT(S): Sixteen healthy female volunteers. INTERVENTION(S): Group 1: one cycle of combined oral contraceptive containing desogestrel (150 microg) and ethinyl estradiol (30 microg) (desogestrel/EE COC), followed by a NuvaRing treatment period. Group 2: NuvaRing treatment period followed by a cycle of desogestrel/EE COC. MAIN OUTCOME MEASURE(S): Follicular diameter, serum hormone concentrations (follicle-stimulating hormone, 17beta estradiol, luteinizing hormone, and progesterone), and endometrial thickness. RESULT(S): NuvaRing use for the recommended period of 3 weeks resulted in complete inhibition of ovulation, as assessed by vaginal ultrasound (follicular diameter) and by serum luteinizing hormone and progesterone concentrations. Inhibition of ovulation was maintained for an additional 2 weeks of NuvaRing use. Ovarian suppression between the groups was comparable. Furthermore, ovarian suppression after 3 weeks of NuvaRing use was comparable to that on day 21 of DGS/EE COC intake. NuvaRing was well tolerated. CONCLUSION(S): NuvaRing completely inhibited ovulation throughout the normal 3-week period and the extended period of use. Ovarian suppression was comparable to that with desogestrel/EE COC.     

高胰岛素血症在多囊卵巢综合征发病中的作用及抗胰岛素的治疗

目的探讨高胰岛素（ＩＮＳ）血症在多囊卵巢综合征（ＰＣＯＳ）发病中的作用及二甲双胍对ＰＣＯＳ的治疗效果。方法将２３例ＰＣＯＳ病人分为肥胖组（１２例）和非肥胖组（１１例）,于服二甲双胍前及服二甲双胍８～１２周后,应用放射免疫法测定基础状态下雄激素、黄体生成素（ＬＨ）、性激素结合球蛋白及促性腺激素释放激素激动剂（ＧｎＲＨａ）刺激后,血１７α羟孕酮（１７ＯＨＰ）和ＬＨ的水平、口服糖耐量试验（ＯＧＴＴ）中血ＩＮＳ水平。结果用药后肥胖组空腹血ＩＮＳ水平和非肥胖组ＯＧＴＴ时血ＩＮＳ反应曲线下面积均明显下降;两组基础状态下的血１７ＯＨＰ、雄烯二酮（Ａ）、睾酮（Ｔ）水平均显著下降、性激素结合蛋白水平显著增加;ＬＨ基值及ＧｎＲＨａ刺激后的ＯＨＰ和ＬＨ值均无明显变化。结论高ＩＮＳ血症在ＰＣＯＳ的高雄激素血症起重要作用,二甲双胍可用于ＰＣＯＳ的治疗