The comparison of the effectiveness and safety of drospirone ethinyl estradiol and ethinyl estradiol cyproterone in the treatment of polycystic ovarian syndrome: A protocol for systematic review and meta-analysis.

BACKGROUND: Polycystic ovarian syndrome (PCOS) is an endocrine disorder syndrome with reproductive dysfunction and abnormal glucose metabolism. Persistent non-ovulation, excessive androgens and insulin resistance are important features and they are the most common causes of menstrual disorders in women during childbearing years. At present, the cause of PCOS is not clinically clear. Current studies suggest that it may be due to the interaction of certain genetic genes with environmental factors. It is an important cause of infertility or early miscarriage with the characteristics of various causes and complex clinical manifestations. At present, for the treatment of PCOS patients, clinical treatment mainly includes hypoglycemia, insulin and menstrual regulation and other symptomatic and supportive treatment. Drospirone ethinyl estradiol and ethinyl estradiol cyproterone are 2 of the most commonly used drugs in clinical treatment of PCOS, but there is lack of the evidence of evidence-based medicine. Therefore, this study systematically evaluates the therapeutic effect and safety of PCOS patients with 2 short-acting oral contraceptives, drospirone ethinyl estradiol and ethinyl estradiol cyproterone, which provides the guidance for clinically selecting the appropriate drug to treat PCOS. METHODS: Searching CNKI, WanFang Data, VIP, SinoMed, PubMed, EMbase, Web of Science, and The Cochrane Library database by computer, collecting the randomized controlled studies of DEE and EEC in the treatment of PCOS. The retrieval time limit is from the establishment of each database to July 1, 2020. In addition, tracing the references incorporated into the literature to supplement to the relevant literature. Using the retrieval method by combining the free words and the subject words, and the individual search of different databases is carried out. Meta-analysis is performed using RevMan 5.3 software after 2 researchers independently screens the literature, extracts the data, and evaluates the bias risk included in the study. RESULTS: This study will systematically evaluate the DEE and EEC in the treatment of PCOS by collecting the required evidence to understand the effects of the 2 drugs on hypersotrophicemia, insulin resistance, lipid metabolism, and the safety during drug use in patients of this class, and the results will be published in highly influential academic journals. CONCLUSION: The results of this study will provide theoretical basis for the drug treatment of polycystic ovarian syndrome and provide help in the decision-making of clinical treatment of the disease. ETHICS AND DISSEMINATION: In this study, meta-analysis was used to conduct a second study on the published literature. Therefore, this type of systematic review research does not need to be approved by ethics. OSF REGISTRATION DOI: 10.17605/OSF.IO/8GW9M.

Determinação simultânea de resíduos de etinilestradiol e gestodeno em superfícies de equipamentos de produção / Simultaneous determination of ethynylestradiol and gestodene residues on manufacturing equipment surfaces

Um método de validação de limpeza foi desenvolvido e validado, baseado na amostragem por swab e na determinação cromatográfica simultânea de resíduos de gestodeno e etinilestradiol. O método apresenta limite de quantificação de 0,036µg/mL de etinilestradiol e 0,009µg/mL de gestodeno. Este foi considerado seletivo, preciso, exato e robusto de acordo com as normas da ANVISA. O fator de recuperação para etinilestradiol foi 90,45% e para gestodeno foi 83,52% em superfície de inox e 87,31% para etinilestradiol e 81,21% para gestodeno em superfície emborrachada. O método foi aplicado com sucesso no teste de amostragem por swab de todos os pontos de superfície dos equipamentos. O método de limpeza foi considerado validado...

A cleaning technique validation method was developed and validated, based on swab sampling and simultaneous chromatographic determination of gestodene and ethynyl estradiol residues. The method exhibited limits of quantitation (LOQs) of 0.036µg/mL for ethynyl estradiol and 0.009µg/mL for gestodene. It was considered selective, precise, accurate and robust, according to the standards set by ANVISA, the Brazilian regulatory agency. Mean swab recovery factors were 90.45% for ethynyl estradiol and 83.52 % for gestodene on an inox surface and 87.31% for ethynyl estradiol and 81.21 % for gestodene on a rubberized surface. The method was successfully applied to the assay of actual swab samples collected from all points on equipment surfaces. The cleaning method was validated...

Improving the efficiency of ion mobility spectrometry analyses by using multivariate calibration.

The simplicity, sensitivity and expeditiousness of ion mobility spectrometry (IMS) make it especially useful for the determination of active principal ingredients (APIs) present at low concentrations in pharmaceuticals. However, the poor resolution of this technique precludes the identification and/or determination of substances with similar molecular weights, which exhibit also similar drift times and give overlapped peaks as a result. Oral contraceptives are pharmaceutical formulations containing two APIs of similar molecular weights at very low concentrations which therefore give strongly overlapped peaks hindering their determination by IMS. In this work, we assessed the potential of IMS for detecting and quantifying the contraceptives ethinylestradiol (ETE) and desogestrel (DES) in commercial tablets. To this end, we used various chemometric techniques including a second-derivative (TN2D) algorithm and the more powerful choice Multivariate Curve Resolution (MCR) to improve the resolution of IMS and enable the determination of both APIs. Quantitation was based on PLS1 models for each API. The models constructed involve a single PLS factor with a Y-explained variance above 98.4%, obtaining a RMSEP of 0.34 and 0.63 for ETE and DES, respectively. The ensuing method, which was validated for use in routine analyses, is quite expeditious (analyses take less than 1 min) and uses very small amounts of sample (a few microliters). Based on the results, IMS has a great potential for the qualitative and quantitative determination of APIs in low doses.

Ethinylestradiol and levonorgestrel preparations on the Belgian market: a comparative study.

Preparations formulated as coated or film-coated tablets, containing levonorgestrel and the combination ethinylestradiol/levonorgestrel, were evaluated in a comparative study. This study comprised in vitro dissolution, assay and content uniformity. The analytical methods were previously validated according to international guidelines. All examined products complied with the postulated requirements.

Bleeding pattern, tolerance and patient satisfaction with a drospirenone-containing oral contraceptive evaluated in 3488 women in Europe, the Middle East and Canada.

BACKGROUND: This study was conducted to assess the bleeding pattern, tolerance and patient satisfaction associated with an oral contraceptive (OC) containing 3 mg of drospirenone and 30 mcg of ethinyl estradiol under real-life conditions. STUDY DESIGN: A multicenter, prospective and observational six-cycle study was conducted in 12 countries in Europe, the Middle East and Canada. The efficacy variables included an assessment of bleeding patterns, premenstrual symptoms of water retention and patient satisfaction as determined by a visual analog scale. RESULTS: A total of 3488 women was enrolled in the study. The percentage of women with intermenstrual bleeding decreased from 27.9% at baseline to 5.4% at the end of Cycle 6, while dysmenorrhea decreased from 67% to 17.7%. Also, amenorrhea decreased from 21.3% to 7.5%. The decreases in all three parameters were statistically significant (p<.0001). Approximately 70% of the women reported abdominal bloating and/or breast tenderness at baseline and less than 38% did so at the end of Cycle 6 (p<.0001). Patient satisfaction increased for all investigated items. Upon completion of the study, 86.2% of the women answered "yes" to continuing treatment with this OC. CONCLUSION: The OC containing 3 mg of drospirenone and 30 mcg of ethinyl estradiol has beneficial effects on bleeding pattern, symptoms of water retention and patient satisfaction.

Efficacy and safety of a low-dose 24-day combined oral contraceptive containing 20 micrograms ethinylestradiol and 3 mg drospirenone.

The aim of this open-label, multicenter, noncomparative study was to determine the efficacy, safety and bleeding profile of a new low-dose, monophasic combined oral contraceptive containing 20 micrograms ethinylestradiol and 3 mg drospirenone administered daily for 24 days followed by a 4-day hormone-free interval. Contraceptive efficacy was analyzed for 1018 women completing 11,140 treatment cycles. Eleven pregnancies occurred, giving a Pearl Index (PI) of 1.29 (upper limit of the 95% confidence interval [CI], 2.30); of these pregnancies, five were considered due to method failure, giving an adjusted PI of 0.72 (upper limit of the 95% CI, 1.69). A total of 7 (0.7%) women discontinued study medication because of irregular bleeding, suggesting a favorable bleeding profile. Overall, the treatment was well tolerated with an excellent safety profile. The majority of women (86%) stated that they were satisfied or very satisfied with the treatment and over 70% of women would have continued with the study medication.

Combined administration of low-dose gossypol acetic acid with desogestrel/mini-dose ethinylestradiol/testosterone undecanoate as an oral contraceptive for men.

To evaluate the efficacy and feasibility of a new regimen of low-dose gossypol acetic acid (GA) combined with desogestrel/ethinylestradiol and testosterone undecanoate (DSG/E/TU) as a male contraceptive, adult male rats were fed orally with GA (12.5 mg/kg/day) and DSG (0.125 mg/kg)/E (0.025 mg/kg)/TU (100 mg/kg) daily for 8 weeks as loading dose until infertility, and a similar low dose of GA alone for infertility maintenance. Control animals were administered a single low dose of GA (12.5 mg/kg/day) or DSG (0.125 mg/kg)/E (0.025 mg/kg)/TU (100 mg/kg), and vehicle, respectively. Results demonstrated that the combined dosage regimen could damage epididymal sperm motility and density, and induce infertility within 8 weeks in rats; the infertility could be consistently sustained by giving single GA (12.5 mg/kg/day), and was reversible in about 8 weeks following withdrawal of gossypol. The regimen rendered treated male rats with spermiation failure within a period of 6-20 weeks of treatment. Also, the serum luteinizing hormone, follicle-stimulating hormone and testicular interstitial fluid testosterone levels showed a transient decrease at the end of 6 or 8 weeks, which returned to control levels after 8 weeks of recovery phase. No hypokalemia or other adverse effects in viscera were observed. These results provide a promising approach to using the new regimen for the development of an effective and reversible oral male contraceptive.

Contraceptive efficacy and cycle control with the Ortho Evra/Evra transdermal system: the analysis of pooled data.

OBJECTIVE: To present efficacy and cycle control data pooled from three pivotal studies of the contraceptive patch (Ortho Evra/Evra). DESIGN: Three multicenter, open-label, contraceptive studies that included up to 13 treatment cycles. SETTING: 183 centers. PATIENT(S): 3,319 women. INTERVENTION(S): Three consecutive 7-day patches (21 days) with 1 patch-free week per cycle. MAIN OUTCOME MEASURE(S): Contraceptive efficacy and cycle control. RESULT(S): Overall and method failure life-table estimates of contraceptive failure through 13 cycles were 0.8% (95% CI, 0.3%-1.3%) and 0.6% (95% CI, 0.2%-0.9%), respectively. Corresponding Pearl indices were 0.88 (95% CI, 0.44-1.33) and 0.7 (95% CI, 0.31-1.10). Contraceptive failure among women with a body weight < 90 kg (<198 lb) was low and uniformly distributed across the weight range. A subgroup of women with body weight > or = 90 kg (> or = 198 lb) may have increased risk of pregnancy. The incidence of breakthrough bleeding was low and decreased over time. CONCLUSION(S): In contraceptive patch users, the overall annual probability of pregnancy was 0.8% and the method failure probability was 0.6%. The efficacy of the patch was high and similar across age and racial groups. Among women < 90 kg (<198 lb), contraceptive failure was low and uniformly distributed across the range of body weights. In women > or = 90 kg (> or = 198 lb), contraceptive failures may be increased. Efficacy and cycle control have been shown to be comparable to an established oral contraceptive.

Low-dose oral contraceptives and bone mineral density: an evidence-based analysis.

We reviewed studies of the association of oral contraceptive (OC) use and bone mineral density (BMD). We limited the review to studies of women using low-dose oral contraceptives and that measured BMD by bone densitometry. A total of 13 studies met the inclusion criteria. Nine of these showed a positive effect of OC use on BMD, and four did not show an association. However, none of the studies showed a decrease in BMD with OC use. We classified the level of evidence from each study according to the guidelines of the US Preventive Services Task Force. The level of evidence supporting a positive association between OC use and increased BMD is II-1. There is fair evidence (Category B) to support the position that OC use has a favorable effect on BMD. We made suggestions for a study design that could yield Level I evidence.

PIP: The authors reviewed studies of the association of oral contraceptive (OC) use and bone mineral density (BMD). They limited the review to studies of women using low-dose OCs and that measured BMD by bone densitometry. A total of 13 studies met the inclusion criteria; 9 of these showed a positive effect of OC use on BMD, and 4 did not show an association. However, none of the studies showed a decrease in BMD with OC use. They classified the level of evidence from each study according to the guidelines of the US Preventive Services Task Force. There is evidence supporting a positive association between OC use and increased BMD. There is fair evidence to support the position that OC use has a favorable effect on BMD. The authors made suggestions for a study design that could yield level I evidence.

An open-label, multicenter study to evaluate Yasmin, a low-dose combination oral contraceptive containing drospirenone, a new progestogen.

This open-label, multicenter study evaluated the efficacy, safety, and cycle control of Yasmin, a new low-dose, monophasic oral contraceptive containing the unique progestogen drospirenone (DRSP) 3 mg and ethinyl estradiol (EE) 30 microg. DRSP is a synthetic progestogen that has antiandrogenic and antimineralocorticoid effects. In this study, 326 women were evaluated and 220 (67%) completed all 13 treatment cycles. The corrected Pearl Index was 0. 407. Of the 151 subjects who experienced intermenstrual bleeding at any time during the study, the majority (64%) had bleeding during only one or two pill cycles. Breakthrough bleeding without spotting occurred in 1% of all cycles, spotting without breakthrough bleeding in 9.3% of all cycles, and breakthrough bleeding with spotting in 3% of all cycles. Amenorrhea was observed in 3% of all cycles. In all, 20 subjects (6%) discontinued participation in the study because of adverse events. No serious adverse events related to the study drug were reported. No clinically significant changes in weight, blood pressure, or lipids were reported. The impact of the new progestogen DRSP on the women's self-perception of menstrual health was also evaluated. Subjects reported that symptoms of water retention, negative affect, and increased appetite significantly improved at cycle 6 from baseline. This study demonstrates that Yasmin is an effective oral contraceptive that is safe and well tolerated.

Efficacy, cycle control, and side effects of low- and lower-dose oral contraceptives: a randomized trial of 20 micrograms and 35 micrograms estrogen preparations.

Estrogen content represents a tradeoff between cycle control and side effects, but few direct comparisons of 20 and 30/35 micrograms preparations are available. To address this issue, we conducted a randomized, open-label multicenter clinical trial comparing Alesse (20 micrograms ethinyl estradiol [EE]), Mircette (20 micrograms EE), and Ortho Tri-Cyclen (35 micrograms EE) among 463 OC starters or switchers. Bloating, breast tenderness, and nausea were approximately 50% more common in women using 35 micrograms EE as compared to 20 micrograms EE preparations. Cycle control was similar in all products, although during the first two cycles among starters; users of Mircette and Ortho Tri-Cyclen (Tri-Cyclen) exhibited better cycle control than Alesse users. Discontinuation and pregnancy rates were not significantly higher in 35 micrograms EE users.

PIP: Estrogen content represents a tradeoff between cycle control and side effects, but few direct comparisons of 20 and 30/35 mcg preparations are available. To address this issue, researchers conducted a randomized, open-label multicenter clinical trial comparing Alesse (20 mcg ethinyl estradiol [EE]), Mircette (20 mcg EE), and Ortho Tri-Cyclen (35 mcg EE) among 463 oral contraceptive starters or switchers. Bloating, breast tenderness, and nausea were approximately 50% more common in women using 35 mcg EE as in those using 20 mcg EE preparations. Cycle control was similar in all products, although during the first two cycles among starters, users of Mircette and Ortho Tri-Cyclen (Tri-Cyclen) exhibited better cycle control than Alesse users. Discontinuation and pregnancy rates were not significantly higher in 35 mcg EE users.

Consensus statement on emergency contraception.

Twenty-four experts from around the world, representing the fields of research, policy, communications, women's advocacy and medicine, gathered at the Rockefeller Foundation Conference Center in Bellagio, Italy, in April 1995 to discuss emergency contraception. The conference was hosted by South-to-South Cooperation in Reproductive Health and co-sponsored by the International Planned Parenthood Federation, Family Health International, the Population Council and the World Health Organization. The conference was supported by the Rockefeller Foundation.

A twelve-month comparative clinical investigation of two low-dose oral contraceptives containing 20 micrograms ethinylestradiol/75 micrograms gestodene and 20 micrograms ethinylestradiol/150 micrograms desogestrel, with respect to efficacy, cycle control and tolerance.

The aim of this study was to compare contraceptive reliability, cycle control and tolerance of an oral contraceptive containing 20 micrograms ethinylestradiol and 75 micrograms gestodene, with a reference preparation containing the same dose of estrogen combined with 150 micrograms desogestrel. This article presents interim data from centers in France and Austria, involving a total of 479 women and 4,991 cycles. Contraceptive reliability was good with both preparations. Two pregnancies occurred in the gestodene group, but neither were due to method failure. In the desogestrel group there were also two pregnancies, of which one was due to method failure. With respect to cycle control, there is a trend towards a lower incidence of intermenstrual bleeding in the gestodene group. The incidence of spotting (scanty bleeding) during the important first three cycles was 3.5% lower in the gestodene group, and over the first six cycles, it was 7.6% lower. Amenorrhea was similar in both groups, but the incidence of dysmenorrhea was significantly lower in the gestodene group (p=0.001). Adverse events were similar in both groups, with headache, breast tension and nausea the most frequently reported symptoms. Body weight remained relatively constant during treatment in both groups, and no hypertension was reported for any woman during the course of the study. In each treatment group, 19 women discontinued because of adverse events. It is concluded that both preparation are reliable and well tolerated oral contraceptives are reliable and well tolerated oral contraceptives; however, there is a more favourable effect on dysmenorrhea by the gestodene formulation.

The effect on blood pressure of a monophasic oral contraceptive containing ethinylestradiol and gestodene.

To obtain an overview of the effect of monophasic gestodene on blood pressure and to determine the frequency of "OC elevated BP/hypertension," the results of blood pressure monitoring from four clinical studies of contraceptive efficacy and safety have been retrospectively analyzed. A total of 1930 women took part in the studies, which recorded BP for up to 24 cycles. Analysis of results revealed that 97 women (5.0%) showed an increase in blood pressure from previously normal to elevated values while taking monophasic gestodene, with only 26 (1.35%) fulfilling the criteria of "OC elevated BP/hypertension." Only four women dropped out of the trials due to hypertensive blood pressure values, while 67 women (3.5%) experienced a normalization of previously elevated blood pressure measurements. In conclusion, this analysis has confirmed that gestodene has a negligible effect on blood pressure, with increased BP a relatively rare event.

PIP: Schering AG (manufacturer of a monophasic oral contraceptive [OC] containing 75 mcg gestodene plus 30 mcg ethinyl estradiol) in Berlin, Germany, conducted a retrospective analysis of blood pressure measurements from 4 clinical trials of the contraceptive efficacy and safety of monophasic gestodene to examine gestodene's effect on blood pressure and the incidence of OC-related blood pressure/ hypertension. (OC-related blood pressure/hypertension is defined as: women with neither history of hypertension nor elevated blood pressure before OC use develop increased blood pressure or hypertension that is reversible once OC use ceases.) The clinical trials recorded the blood pressure of 1930 women for up to 24 cycles. Most women (89.9%) experienced no change in their blood pressure during OC use. 97 women (5%) experienced an increase in blood pressure. 26 women (1.35%) had OC-elevated blood pressure/hypertension. Four women left the trials due to hypertension. 67 women (3.5%) who had elevated blood pressure before OC use attained normalization of blood pressure during OC use. These results show that the gestodene-containing OC had an insignificant effect on blood pressure and that elevated blood pressure rarely occurred.

Comparative study on intermittent versus continuous use of a contraceptive pill administered by vaginal route.

A multicenter, international, randomized, comparative trial was conducted to assess the acceptability, efficacy and safety of two different schedules of a contraceptive pill, containing 250 micrograms levonorgestrel and 50 micrograms ethinyl estradiol, administered by the vaginal route. One schedule of daily administration for 21 days with a seven-day interruption to allow withdrawal bleeding was compared to daily administration without interruption for bleeding. A total of 900 women were recruited in three countries, Brazil, Egypt and China; 7,090 women-months of vaginal pill use were recorded (3,364 using the pills intermittently and 3,726 continuously). Four undesired pregnancies occurred, one in Egypt and three in China, all four in women using the pills intermittently. There was a statistically significant difference (p = 0.486) in pregnancy rate between the two groups. There were no other significant differences in discontinuation rates despite marked differences in bleeding patterns, amenorrhea predominating in the continuous use group. Hemoglobin levels increased significantly in the two groups but hematocrit was significantly higher in the continuous use group.

PIP: 900 healthy women 16-42 years old were recruited in Brazil, China, and Egypt for a multicenter, randomized, comparative clinical trial to determine the acceptability, efficacy, and safety of two different schedules of a contraceptive pill with 250 mcg levonorgestrel and 50 mcg ethinyl estradiol administered vaginally. The two schedules were: 1) daily vaginal use of the pill for 21 days, followed by withdrawal for regular bleeding, and restarted 7 days later, and 2) use of the pill by the vaginal route nonstop for one year. There were no significant difference in cumulative discontinuation rates between the two groups (total, 15.5 for intermittent group and 14.64 for continuous group), except for unwanted pregnancy. The only unwanted pregnancies occurred to 4 women in the intermittent group (1.04%) (p = 0.0486). Women in the continuous use group were more likely than those in the intermittent group to have spotting at least once (20.6% vs. 4.4%; p 0.001). Women in the continuous group were more likely than those in the intermittent group to have amenorrhea. For example, the mean number of bleeding/spotting days during all time intervals was lower for the continuous group than for the intermittent group (p 0.001; last interval, 0.97 vs. 12.83). Hemoglobin levels increased considerably in both groups between baseline and one year of use (11.61 vs. 11.9 g/dl for intermittent group and 11.54 vs. 11.81 g/dl for continuous use; p 0.001). The mean value of hematocrit at 12 months for the continuous group was higher than that at baseline (38.8% vs. 38.2%; p = 0.011). It did not increase in the intermittent group, however. Women in both groups gained weight during the 12 months of pill use. The weight gain was significant for the continuous group only. These findings suggest that continuous use of vaginal contraceptive pills may be more advantageous than intermittent use oral contraceptives and may benefit anemic women and those who bleed heavily during menstruation.

Climacteric symptoms and control of the cycle in women aged 35 years or older taking an oral contraceptive with 0.150 mg desogestrel and 0.020 mg ethinylestradiol.

In a multicenter prospective trial, 58 healthy women aged between 35 and 49 years were studied for one year (639 cycles) while taking an oral contraceptive (OC) containing desogestrel 0.150 mg and ethinylestradiol (EE) 0.020 mg. Efficacy, control of the cycle, side effects, complaints, and climacteric symptoms were monitored after 3, 6, 9 and 12 cycles. No pregnancies occurred during the study period. Spotting gradually decreased from 29.3% in cycle 1 to 4.2% in cycle 12, while breakthrough bleeding (BTB) disappeared after cycle 7. One case of superficial thrombophlebitis and 3 cases of minor side effects were registered. With regard to the complaints, breast tenderness, headache, and depression gradually decreased during the study (basal vs. 12-month data: 50.9% vs. 31.2%, 48.3% vs. 18.7%, 39.6% vs. 20.8%, respectively), while nausea disappeared after three months. A significant treatment-dependent reduction of climacteric symptoms was obtained after cycle 3 and this tendency was maintained up to cycle 12. No changes were registered in body mass index (BMI) or blood pressure.

Twelve years of clinical experience with an oral contraceptive containing 30 micrograms ethinyloestradiol and 150 micrograms desogestrel.

The clinical experience with a combined oral contraceptive (COC) containing 150 micrograms desogestrel and 30 micrograms ethinylestradiol is reviewed. Fourteen clinical trials have been reported involving over 44,000 women for more than 190,000 cycles. None of the 17 pregnancies which occurred (overall Pearl Index 0.12) were due to method failure. The incidences of breakthrough bleeding and spotting after 6 treatment cycles varied from 0.1-6.0% and 2.8-11% of subjects, respectively, and at this time they were not significantly different from pretreatment in most trials. About 90% of subjects maintained regular cycles. The incidence of subjective side effects (approximately 5% for headache, 4% for breast tenderness, 2% for nausea) was low. No significant changes occurred in body weight or blood pressure. In all trials, the COC was well accepted and the rates of discontinuation were similar to those in other COC trials. Pharmacodynamic effects have been widely investigated. There were no significant changes in glucose metabolism or in haematological factors except for possibly minor increases in factors VII and X, fibrinogen and plasminogen. Over thirty studies of the effect of the COC on lipid metabolism have been published; significant increases occur in serum triglycerides, HDL-C and apoprotein A1. SHBG concentrations increase 2-3 fold with a consequent decrease in the levels of free testosterone. This effect can be particularly important therapeutically in women with hyperandrogenic skin disorders and 14 trials in women with these disorders have demonstrated significant clinical improvement with the COC. The findings from the various trials show the COC to be effective and acceptable with no adverse metabolic effects.

The acceptability of a combined oestrogen/progestogen contraceptive vaginal ring.

The acceptability of a vaginal ring releasing ethinyl oestradiol 20 mcg per day and norethindrone acetate 1 mg per day was assessed during a six-month phase II trial comparing three different regimens, which was carried out simultaneously in Los Angeles and Sydney. Sixty women were enrolled in Sydney and 90 in Los Angeles. On admission into the study, the women were asked to complete a questionnaire which gave details of age, last contraceptive method used, contraceptive methods used in the past and their reason for liking or disliking previous contraceptive methods, as well as their reason for stopping the last method. On completion of the study or leaving the study for any reason, each woman was asked to complete an acceptability questionnaire which included her experiences with the ring and the rating of the method. The responses to these two questionnaires form the basis of this report. The overall rating of the ring was similar in both the Sydney and Los Angeles groups. Sixty-nine percent of women rated the method as very good. Seventy-two percent of women in Los Angeles and 62% of women in Sydney liked the ring much more than their most liked previous method. In both groups the method they liked best apart from the ring was the pill (62% in Sydney and 53% in Los Angeles). The major reasons for liking the ring were convenience of use, effectiveness and no requirements for taking medication daily. Most women in both studies would recommend the ring to others (92% in Sydney and 89% in Los Angeles).

Comparative evaluation of the androgenicity of four low-dose, fixed-combination oral contraceptives.

Changes in endogenous androgen metabolism were compared in healthy women taking one of four low-dose modern oral contraceptives (OCs). One hundred women were randomized to (1) 35 micrograms ethinyl estradiol (EE) + 250 micrograms norgestimate (Cilest); (2) 20 micrograms EE + 150 micrograms desogestrel (Mercilon); (3) 30 micrograms EE + 150 micrograms desogestrel (Marvelon); or (4) 30 micrograms EE + 75 micrograms gestodene (Femodene). During the luteal phase of the pretreatment cycle, body weight and blood pressure were recorded, and plasma levels of the following variables were recorded: sex-hormone-binding globulin (SHBG), cortisol-binding globulin (CBG), testosterone, free testosterone, dihydrotestosterone, androstenedione, dihydroepiandrosterone sulfate (DHEAS), and hydroxyprogesterone. The free androgen index was also calculated. These variables were remeasured during the third week of OC intake and during the fourth and sixth cycles. There were no statistically significant differences in androgenic variables among the four OCs. The DHEAS concentration decreased less with the 20 micrograms EE + desogestrel formulation compared with either 30 micrograms EE + desogesterel or norgestimate-containing formulations (20% vs. 45%). Concentrations of SHBG and CBG increased significantly in all four groups (average 263 +/- 119% and 94 +/- 26%, respectively); CBG increased less in women taking 20 micrograms EE + desogestrel (about 75%) than in the other formulations (about 100%). The four modern, low-dose OCs tested had similar impacts on endogenous androgen metabolism, yielding significant decreases in testosterone, dihydrotestosterone, androstenedione, and DHEAS. All of these formulations may be beneficial in women with androgen-related syndromes such as acne and hirsutism. Large studies are under way to establish which of the third-generation OCs is the least androgenic. In vitro studies suggest that norgestimate has the least androgenic profile.