Combined oral contraceptive pills for treatment of acne.
Topic: Hormone Therapy

Acne is a common skin disorder among women. Although no uniform approach to the management of acne exists, combination oral contraceptives (COCs), which contain an estrogen and a progestin, often are prescribed for women.

PICO
Population: Women with acne
Intervention: Combined oral contraceptive pills
Comparison: Placebo or alternative acne treatment
Outcomes: Improvement in acne severity, reduction in acne lesions, side effects of COCs

Included studies:
title: Comparison of the effect on acne with a combiphasic desogestrel-containing oral contraceptive and a preparation containing cyproterone acetate.
abstract: To investigate the effect of a combiphasic oral contraceptive containing ethinylestradiol and desogestrel (combiphasic EE/DSG) on acne, compared with a preparation containing ethinylestradiol and cyproterone acetate (EE35/CPA).
title: Ethinylestradiol/chlormadinone acetate.
abstract: Ethinylestradiol/chlormadinone acetate 0.03/2mg (EE/CMA) is a combined monophasic contraceptive pill with antiandrogenic properties. In a large, noncomparative, multicentre trial (< or =24 cycles of treatment per woman) and two (6- and 12-cycle) postmarketing surveillance studies, EE/CMA was effective in preventing pregnancy. EE/CMA was significantly more effective than EE/levonorgestrel 0.03/0.15 mg/day in treating women with mild-to-moderate papulopustular acne of the face and related disorders in a randomised, single-blind, multicentre trial. EE/CMA was well tolerated in clinical trials and the postmarketing surveillance studies. Adverse events were those commonly reported with oral contraceptives. As expected, the most common menstrual disturbances were breakthrough bleeding, spotting and amenorrhoea.
title: A randomized double blind study of two oral contraceptives.
abstract: To study the question of whether one brand of oral contraceptives may be as acceptable as another for use of publicly-assisted family planning programs, a double blind study of two well-known brands, Ovral and Norinyl, was undertaken in Costa Rica and Trinidad. The pills were randomly assigned to 1,200 women. Common side effects - nausea, dizziness, vomiting, headaches - were associated with both Norinyl and Ovral. Differences in event rates for these conditions were much more marked by country than by the pill used. Ovral was associated with increases in skin problems, notably chloasma, in Cost Rica. A higher percentage of women using Norinyl reported intermenstrual bleeding and spotting in both countries. In Costa Rica continuation rates for Norinyl were adversely affected by this. With these exceptions there appear to be no important differences between the brands that would affect their use in family planning programs.
title: Treatment of moderate acne vulgaris using a combined oral contraceptive containing ethinylestradiol 20 μg plus drospirenone 3mg administered in a 24/4 regimen: a pooled analysis.
abstract: To investigate the effects of an ethinylestradiol (EE) 20 μg/drospirenone (drsp) 3mg combined oral contraceptive (COC) administered in a 24/4 regimen (24 active tablets/4 inert tablets per cycle) for the treatment of moderate acne vulgaris, based on a pooled analysis of two identically designed US studies.
title: Effects on acne of two oral contraceptives containing desogestrel and cyproterone acetate.
abstract: To compare the effects of a low-dose oral contraceptive containing desogestrel (Marvelon) and an anti-androgenic preparation containing cyproterone acetate (Diane) in Oriental women suffering from acne.
title: An open randomized comparative study of an oral contraceptive containing ethinyl estradiol and cyproterone acetate with and without the GnRH analogue goserelin in the long-term treatment of hirsutism.
abstract: A multicenter randomized study was carried out to compare the efficacy of combined therapy with a GnRH analog (goserelin) + an oral contraceptive (OC) containing ethinyl estradiol and cyproterone acetate and same OC alone in the treatment of severe hirsutism. The effect of these two therapies was assessed in a subjective and an objective evaluation of hair growth. According to the subjective evaluation, judged by physician and patient. 95% of patients obtained a partial response. The objective response was assessed by measuring the mean diameter of hair from 3 different areas and 1 control area. The decrease in hair diameter compared to pretreatment was statistically significant for both treatments, mainly for the abdomen and face. The difference between the two groups did not reach statistical significance. Therefore, we assume that OC alone remains the treatment of choice for hirsutism. However, the addition of the GnRH analog to OC needs further investigation and could be justified for patients with no response to standard monotherapy.
title: Effectiveness of norgestimate and ethinyl estradiol in treating moderate acne vulgaris.
abstract: An excess of androgen is believed to contribute to development of acne in some patients. Because oral contraceptives (OCs) may reduce the active androgen level, hormonal therapy with OCs has been used successfully to treat patients with acne, although this treatment has previously not been studied in placebo-controlled trials.
title: The influence of Microgynon and Diane-35, two sub-fifty ovulation inhibitors, on voice function in women.
abstract: The early days of oral contraceptives showed some evidence that these medications may have caused undesirable side effects on the voice, mainly in terms of virilization. In a random study carried out at the university hospitals of Jena and Berlin (Charité), two more recent drugs were tested in this regard, one containing cyproterone acetate (Diane-35) and the other one levonorgestrel (Microgynon), both from Schering. Ninety-one patients took part in extensive clinical and instrumental phoniatric investigations of voice function over a period of one year. No significant side effects on the voice could be proven for the two preparations. Gynecological and clinical effects of both Diane-35 and Microgynon were similar during the one-year study period. Women taking Diane-35 had less intracyclic bleedings and amenorrhea. Also, acne was more favorably influenced by Diane-35.
title: [Clinical evidence of the minimal androgenic activity of norgestimate].
abstract: The aim for improving the progestogen component of oral contraceptives is both to increase their selectivity by obtaining a highly effective contraceptive action and to decrease the side effects related to the existing progestogens. The androgenic activity of the existing progestogens modifies the lipid metabolism, particularly a decrease in the high density lipoprotein (HDL) level, which increases the risks of cardiovascular diseases. Thus, the discovery of a progestogen with good anti-ovulatory and minimal androgenic properties would constitute an important progress in the field of oral contraception. Norgestimate (NGM) is a new progestogen presenting an exceptional profile of biological activity, and has proved to be extremely selective, as observed during the clinical trials. The studies described below have been carried out in order to confirm clinically the low androgenic activity of NGM. In two clinical trials, Norgestimate (0.25 mg) associated with 0.035 mg of ethinyloestradiol (NGM 0.25/35) was compared to norgestrel (0.30 mg) associated with 0.030 mg of ethinyloestradiol (Lo/Ovral). In the first trial (1,261 women), the following observations were made: an important increase in the HDL level compared to the base levels in the subjects taking NGM 0.25/35, and an important decrease in the HDL level in those taking Lo/Ovral. The low density lipoprotein (LDL) level increased slightly in the NGM 0.25/35 group, while a higher increase was observed in the Lo/Ovral group. Moreover, the LDL/HDL ratio translates a more favourable lipid profile in the NGM 0.25/35 group, since the values are lower than those observed for the Lo/Ovral group.(ABSTRACT TRUNCATED AT 250 WORDS)
title: Oral contraceptives and venous thromboembolism: a five-year national case-control study.
abstract: The objective of this study was to assess the influence of oral contraceptives (OCs) on the risk of venous thromboembolism (VTE) in young women. A 5-year case-control study including all Danish hospitals was conducted. All women 15-44 years old, suffering a first ever deep venous thrombosis or a first pulmonary embolism (PE) during the period January 1, 1994, to December 30, 1998, were included. Controls were selected annually, 600 per year in 1994-1995 and 1200 per year 1996-1998. Response rates for cases and controls were 87.2% and 89.7%, respectively. After exclusion of nonvalid diagnoses, pregnant women, and women with previous thrombotic disease, 987 cases and 4054 controls were available for analysis. A multivariate, matched analysis was performed. Controls were matched to cases within 1-year age bands. Adjustment was made for confounding influence (if any) from the following variables: age, year, body mass index, length of OC use, family history of VTE, cerebral thrombosis or myocardial infarction, coagulopathies, diabetes, years of schooling, and previous birth. The risk of VTE among current users of OCs was primarily influenced by duration of use, with significantly decreasing odds ratios (OR) over time: <1 year, 7.0 (5.1-9.6); 1-5 years, 3.6 (2.7-4.8); and >5 years, 3.1 (2.5-3.8), all compared with nonusers of OCs. After adjustment for confounders, current use of OCs with second- (levonorgestrel or norgestimate) and third- (desogestrel or gestodene) generation progestins when compared with nonuse resulted in ORs for VTE of 2.9 (2.2-3.8) and 4.0 (3.2-4.9), respectively. After adjusting for progestin types and length of use, the risk decreased significantly with decreasing estrogen dose. With 30-40 microg as reference, 20 and 50 microg products implied ORs of 0.6 (0.4-0.9) and 1.6 (0.9-2.8), respectively (p(trend) = 0.02). After correction for duration of use and differences in estrogen dose, the third/second-generation risk ratio was 1.3 (1.0-1.8; p <0.05). In conclusion, use of OCs was associated significantly to the risk of VTE. The risk among current users was reduced by more than 50% during the first years of use. The risk increased more than 100% with increasing estrogen dose, and the difference in risk between users of third- and second-generation OCs, after correction for length of use and estrogen dose, was 33%.
title: Efficacy of low-dose cyproterone acetate compared with minocycline in the treatment of acne vulgaris.
title: The development and evaluation of an ovulation inhibitor (DIAne) containing an antiandrogen.
abstract: The combination of 2 mg cyproterone acetate, a pronounced antiandrogenic substance, in combination with 0.05 mg ethinyl estradiol has undergone intensive multiphasic clinical evaluation. The preparation with the trade name Diane has proven to be not only a reliable contraceptive, but also a very potent drug for the treatment of both acne and seborrhea, and of milder cases of hirsutism. The effect of Diane on markedly increased hair growth was not so pronounced. In addition to the presentation of the most pertinent steps of the clinical investigation of Diane, the possible mode of actions of antiandrogens alone and in combination with an estrogen is discussed.
title: Multicenter trial of two monophasic oral contraceptives containing 30 mcg ethinylestradiol and either desogestrel or gestodene in Thai women.
abstract: The efficacy and acceptability of two third generation oral contraceptives in Thai women were evaluated in a prospective, open, group-comparative, randomized, multicenter trial of women asking for contraception. In six Family Planning Centers and Outpatient Gynaecological Clinics in urban areas in Thailand, 783 healthy women who were at risk for pregnancy and did not have contraindications to oral contraceptive use were randomly allocated to one of the two study groups. An oral contraceptive containing 30 mcg ethinylestradiol and 150 mcg desogestrel was given to 394 women and an oral contraceptive with the same amount of ethinylestradiol and 75 mcg gestodene to 389 women during 6 cycles. Criteria of cycle control, side effects and the presence and severity of acne vulgaris were assessed and blood pressure and body weight measured at pretreatment and after cycles 1, 3 and 6. Furthermore, the efficacy was evaluated after the last cycle. No pregnancies occurred with either of the contraceptives. The incidences of irregular bleeding and minor side effects in both groups were very low and decreased after an initial increase in the first cycle. Acne improved in both groups. Blood pressure and body weight remained unchanged. The two oral contraceptives were found to be effective and acceptable in Thai women. Compared to Caucasian women, the incidences of irregular bleeding and side effects were apparently lower in these Asian women. Furthermore, the effects of both oral contraceptives were comparable.
title: Effect of low-dose oral contraceptives on androgenic markers and acne.
abstract: Oral contraceptives (OC) suppress excess androgen production; however, different progestins in combination with low-dose estrogens produce divergent effects on sex hormone-binding globulin (SHBG) and testosterone that may influence clinical outcomes. This multicenter, open-label, randomized study compared biochemical androgen profiles and clinical outcomes associated with two OC containing the same amounts of ethinyl estradiol (EE, 20 micrograms) but different progestins, levonorgestrel (LNG, 100 micrograms), and norethindrone acetate (NETA, 1000 micrograms). Fifty-eight healthy women (18-28 years old) received three cycles of treatment with LNG/EE (n = 30) or NETA/EE (n = 28). The results showed that LNG reduced androgen levels in three compartments--adrenal, ovarian, and peripheral. NETA reduced only adrenal and peripheral androgens. Despite a 2.2-fold greater relative increase in SHBG with NETA than LNG, bioavailable testosterone (T) was reduced by the same amount with LNG and NETA. Both treatments improved acne and were well tolerated. Low-dose OC (EE, 20 micrograms) are effective in reducing circulating androgens and acne lesions without causing weight gain. Although LNG and NETA affected secondary markers differently, both OC formulations produced an equivalent decrease in bioavailable.
title: Blinding in randomised trials: hiding who got what.
abstract: Blinding embodies a rich history spanning over two centuries. Most researchers worldwide understand blinding terminology, but confusion lurks beyond a general comprehension. Terms such as single blind, double blind, and triple blind mean different things to different people. Moreover, many medical researchers confuse blinding with allocation concealment. Such confusion indicates misunderstandings of both. The term blinding refers to keeping trial participants, investigators (usually health-care providers), or assessors (those collecting outcome data) unaware of the assigned intervention, so that they will not be influenced by that knowledge. Blinding usually reduces differential assessment of outcomes (information bias), but can also improve compliance and retention of trial participants while reducing biased supplemental care or treatment (sometimes called co-intervention). Many investigators and readers naïvely consider a randomised trial as high quality simply because it is double blind, as if double-blinding is the sine qua non of a randomised controlled trial. Although double blinding (blinding investigators, participants, and outcome assessors) indicates a strong design, trials that are not double blinded should not automatically be deemed inferior. Rather than solely relying on terminology like double blinding, researchers should explicitly state who was blinded, and how. We recommend placing greater credence in results when investigators at least blind outcome assessments, except with objective outcomes, such as death, which leave little room for bias. If investigators properly report their blinding efforts, readers can judge them. Unfortunately, many articles do not contain proper reporting. If an article claims blinding without any accompanying clarification, readers should remain sceptical about its effect on bias reduction.
title: Ovulation inhibitors containing cyproterone acetate or desogestrel in the treatment of hyperandrogenic symptoms.
abstract: An open, randomized, multicenter study was carried out to compare two oral contraceptives as regards their therapeutic efficacy in androgenization symptoms such as acne, seborrhea and hirsutism in women. The preparations used were the combination of 2 mg cyproterone acetate (CPA) with 0.035 mg ethinyl estradiol (EE) (Diane 35, Schering AG, Berlin-West) and 0.150 mg desogestrel (DG) with 0.03 mg ethinyl estradiol (Marvelon, Organon, Oss, The Netherlands). The duration of therapy was 9 months. The combination of CPA-EE was used by 83 patients for 658 cycles and the combination of DG-EE by 79 women for 618 cycles. No pregnancy occurred under either therapy. Both preparations are well tolerated. However, some side-effects, such as reduced libido, nervousness and breast tenderness, were observed more frequently (p less than 0.05) in the DG-EE group than among the users of the CPA-EE combination. The therapeutic outcome was better in the CPA-EE group, especially in cases of facial acne (p less than 0.05). Seborrheic symptoms also responded better to the CPA-EE therapy. The results show that the CPA-EE combination is superior to the DG-EE combination in the treatment of acne and seborrhoea.
title: Analytical theory for extracellular electrical stimulation of nerve with focal electrodes. I. Passive unmyelinated axon.
abstract: The cable model of a passive, unmyelinated fiber in an applied extracellular field is derived. The solution is valid for an arbitrary, time-varying, applied field, which may be determined analytically or numerically. Simple analytical computations are presented. They explain a variety of known phenomena and predict some previously undescribed properties of extracellular electrical stimulation. The polarization of a fiber in an applied field behaves like the output of a spatial high-pass and temporal low-pass filter of the stimulus. High-frequency stimulation results in a more spatially restricted region of fiber excitation, effectively reducing current spread relative to that produced by low-frequency stimulation. Chronaxie measured extracellularly is a function of electrode position relative to the stimulated fiber, and its value may differ substantially from that obtained intracellularly. Frequency dependence of psychophysical threshold obtained by electrical stimulation of the macaque cochlea closely follows the frequency dependence of single-fiber passive response.
title: Acne resolution rates: results of a single-blind, randomized, controlled, parallel phase III trial with EE/CMA (Belara) and EE/LNG (Microgynon).
abstract: Acne in women can often be successfully treated by the intake of oral contraceptives containing gestagens with anti-androgenic properties. This study aimed to evaluate the efficacy of the monophasic oral contraceptive ethinylestradiol/chlormadinone acetate (EE/CMA; Belara for the treatment of mild to moderate papulopustular acne of the face and acne-related disorders in comparison to EE/levonorgestrel (LNG; Microgynon.
title: A randomized controlled trial of second- versus third-generation oral contraceptives in the treatment of acne vulgaris.
abstract: This study was undertaken to compare the clinical efficacy of second- versus third-generation oral contraceptives in the treatment of acne.
title: Pituitary function and DHEA-S in male acne and DHEA-S, prolactin and cortisol before and after oral contraceptive treatment in female acne.
abstract: Pituitary function (TRH-LHRH stimulation test) was investigated in male acne patients and serum levels of dehydroepiandrosterone sulphate (DHEA-S), sex hormone binding globulin (SHBG) and other biochemical parameters were investigated in male acne patients and in female acne patients before and after treatment with an oral contraceptive. The TRH-LHRH stimulation test was performed with 15 male patients suffering from severe cystic acne and 7 healthy volunteers. Basal and stimulated prolactin, LH and FSH levels were statistically similar in the patients and control groups. However, the stimulated LH levels of the patients were 60% higher than those in controls. SHBG levels were significantly) higher in the patient group compared to those in the control group. Thirty-three female acne patients were randomly divided into two groups and treated for six months with an oral contraceptive containing 0.030 mg ethinylestradiol (EE) plus 0.150 mg levonorgestrel or 0.150 mg levonorgestrel. After six months' treatment a 30% decrease in DHEA-S levels were observed in the desogestrel/EE group and a 15% decrease in the levonorgestrel/EE group; the difference was not statistically significant. At the same time serum total cortisol increased by 75-100% and free testosterone fell by 30-40% in both groups, whereas SHBG elevated 250% in the desogestrel/EE group and 30% in the levonorgestrel/EE group. Acne improved significantly in both groups, desogestrel/EE showing greater improvement. A decrease in SHBG and increase in DHEA-S levels appear to be the most common hormonal changes in acne. Oral contraceptive treatment induces an increase in SHBG and decrease in DHEA-S and also improves acne.
title: Clinical and hormonal effects of ethinylestradiol combined with gestodene and desogestrel in young women with acne vulgaris.
abstract: The effect of gestodene 75 micrograms (GTD) versus desogestrel 150 micrograms (DSG) combined with 30 micrograms of ethinylestradiol (EE) on acne lesions and plasma androstenedione (A), total testosterone (T), sex hormone binding globulin (SHBG) and "free androgen index" (FAI) was evaluated in an open study on 19 patients aged 18-35 years affected with postpubertal or persistent non-severe acne vulgaris. The patients were randomly allocated into two groups receiving EE-GTD (n = 8) and EE-DSG (n = 11), 21 tablets per cycle for 9 consecutive cycles. Clinical and hormonal evaluations were made between days 17-21 in the cycle before treatment and between days 17-21 of the cycle 3, 6 and 9 of treatment. During treatment, acne improved in most patients, reaching at cycle 9 a low score (absent or minimal) in 62% of the cases in the GTD group (mean acne score = 1.25) and in 90% of the cases in the DSG group (mean acne score = 0.90). Before treatment, about 75% of the patients showed one or more signs of biochemical hyperandrogenism, including elevated FAI (57%), elevated A (15%), elevated total T (15%) and decreased SHBG (21%), and there was evidence of inverse correlation between SHBG and acne scores (p < 0.05). The echogenic texture of the ovaries was multifollicular in 55% of the cases. By the end of the third cycle of treatment, the hormonal changes observed in both groups included significant decreases, with normalization of individual elevated levels of T, and a 3-fold rise of the initial values of plasma SHBG, which showed a further gradual increase at cycle 9 of EE-DSG administration. At cycle 9, normalization of the echogenic ovarian texture was observed. Acne improvement under treatments with estrogen and progestin (EP) could be significantly correlated with the normalization of biochemical hyperandrogenism. In conclusion, the biochemical and clinical efficacy of EE-GTD and EE-DSG indicate that both these preparations can be a good choice in the therapy of acne vulgaris, with a non-significant better clinical result with EE-DSG.
title: Acne: double blind clinical and laboratory trial of tetracycline, oestrogen-cyproterone acetate, and combined treatment.
abstract: Since the recent introduction of a drug regimen containing 2 mg of the antiandrogen cyproterone acetate and 50 micrograms ethinyl-oestradiol (Diane; oestrogen-cyproterone acetate) several uncontrolled reports have extolled the benefits of this drug. Double blind studies, however, are lacking. Sixty two patients with moderate or moderately severe acne were therefore included in a double blind trial of treatment for six months comparing tetracycline alone, oestrogen-cyproterone acetate alone, and a combination of these agents. Sebum excretion rates and bacterial counts were measured before, during, and after treatment, at the same time as a clinical assessment was made. At six months the acne (as assessed by overall grade) had improved by 68% in the antibiotic treated group and by 74% in the oestrogen-cyproterone treated group. The group given a combination of both agents improved by 82%, which was significantly better (p less than 0.025) than the improvement in the tetracycline treated patients. No significant difference was found between the groups given oestrogen-cyproterone alone and the combined treatment. The sebum excretion rate was suppressed by 25% in the patients in both groups receiving oestrogen-cyproterone but not in the group given antibiotics alone. Oestrogen-cyproterone acetate is as effective as antibiotics in treating acne in women, and adding antibiotics offers no advantage over using oestrogen-cyproterone on its own, although in this study the combination was more effective than tetracycline alone at six months.
title: Have oral contraceptives reduced the prevalence of acne? a population-based study of acne vulgaris, tobacco smoking and oral contraceptives.
abstract: The prevalence of acne among adolescents appears to vary geographically. This study was therefore undertaken to describe the prevalence rate of acne among Danish adolescents and to study the possible influence of oral contraceptives (OC) and tobacco smoking on disease prevalence and severity. Both have been suggested to influence acne and are therefore potential confounders in studies of acne prevalence.
title: Topical cyproterone acetate treatment in women with acne: a placebo-controlled trial.
abstract: To evaluate the clinical and hormonal response of topically applied cyproterone acetate, oral cyproterone acetate, and placebo lotion in women with acne.
title: The association of serum androsterone glucuronide with inflammatory lesions in women with adult acne.
abstract: Serum androsterone glucuronide (AoG) is a metabolite of circulating androgens under the influence of 5alpha-reductase activity and has been shown to be particularly elevated in women with acne. In this study, we wanted to evaluate changes in AoG before and after treatment with an oral contraceptive or placebo, and to assess whether changes correlated with the number and type of acne lesions. In order to accomplish these aims, we obtained sera from a completed prospective randomized trial, which was designed to assess the effectiveness of an oral contraceptive compared to placebo. Assessments were carried out in 56 women with moderate acne who were treated with Ortho Tri-Cyclen (norgestimate and ethinylestradiol) (30 patients) or placebo (26 patients) for 6 months. Before and after treatment, the number and type of skin lesions, serum levels of total T, free-T, DHEAS and AoG were determined. Serum AoG increased significantly in women with moderate acne, although T, free-T and DHEAS were normal. 75% of acne patients had elevated levels of serum AoG. Ratios of serum AoG to androgen precursors were also elevated. Oral contraceptive (OC) treatment significantly reduced levels of free-T and AoG, both of which were unaffected by placebo. While both OC and placebo treatment resulted in improvement of comedones and inflammatory lesions, OC treatment decreased inflammatory lesions to a greater extent (p<0.05). After treatment, serum AoG correlated with the number of inflammatory lesions. Results showed that serum AoG is a sensitive marker of acne in women, even in those with normal circulating precursor androgens; and is lowered by OC treatment, correlating with the reduction of inflammatory lesions. We hypothesize that the increase of serum AoG in normoandrogenic acne may be related to inflammation, and serum AoG may serve as a marker of this process.
title: Treatment of acne using a 3-milligram drospirenone/20-microgram ethinyl estradiol oral contraceptive administered in a 24/4 regimen: a randomized controlled trial.
abstract: To assess the efficacy of the combined oral contraceptive containing 3-mg drospirenone/20-microgram ethinyl estradiol (3-mg drospirenone/20-microgram ethinyl estradiol) administered as 24 consecutive days of active treatment after a 4-day hormone-free interval (24/4 regimen) compared with placebo for the treatment of moderate acne vulgaris.
title: Serum total and unbound testosterone and sex hormone binding globulin (SHBG) in female acne patients treated with two different oral contraceptives.
abstract: Serum total an unbound testosterone (T) and sex hormone binding globulin (SHBG) levels were studied in fifty-four female acne patients before treatment and during the treatment by two different oral contraceptives, the other containing 0.150 mg desogestrel plus 0.03 mg EE and the other 0.150 mg levonorgestrel plus 0.03 mg EE. Pretreatment values were abnormal in 57% of the patients. A borderline significant correlation between the severity of acne and SHBG was found. Ater six months' treatment a 250% increase in SHBG was seen in desogestrel/EE group and no significant change in SHBG in levonorgestrel/EE group. However, at the same time serum free testosterone fell 60% in both treatment groups. SHBG cannot be the only regulator of serum free testosterone. Acne improved significantly in both treatment groups. It is likely that the improvement was in connection with the free testosterone decrease and the improvement was better in the desogestrel/EE group where also SHBG elevation was seen.
title: Cyproterone acetate versus levonorgestrel combined with ethinyl estradiol in the treatment of acne. Results of a multicenter study.
abstract: In spite of an abundant literature on antiandrogen treatment with cyproterone acetate (CA) there have been no objectively measured results to prove statistically the possible superiority of CA over combined oral contraceptive pills in the treatment of acne vulgaris. A multicenter study was therefore done, in which two preparations containing CA in combination with ethinylestradiol (EE) were compared with a marketed combined oral contraceptive pill. The preparations studied were: CA 2 mg + EE 50 micrograms (Diane), CA 2 mg + EE 35 micrograms (Diane mite), Levonorgestrel 150 micrograms + EE 30 micrograms (Neovletta). A woman was eligible for the study if she was found by a dermatologist to have at least eight acne lesions (sum of papules, pustules, cysts and nodules) on her face, was otherwise healthy and without medication. After a primary assessment of the number of acne lesions by the dermatologist the woman was referred to a gynecologist and given one of the three test preparations double-blind and at random. The treatment was to continue for 6 months. 133 women were recruited at eight different centers. The groups thus constituted were of similar size and comparable with regard to age, degree of acne, and menstrual and contraceptive histories. As the number of acne lesions varied considerably between patients all data were converted into percentage change during treatment before they were processed in a computer. After only 4 months of treatment the patients on Diane and Diane mite had a significantly greater reduction in the number of acne lesions compared with those on Neovletta.(ABSTRACT TRUNCATED AT 250 WORDS)
title: Anti-androgen treatment in women with acne: a controlled trial.
abstract: Ninety female patients with acne were allocated randomly to one of three groups and treated either with Diane, a high dose cyproterone acetate (CPA) regime with ethinyloestradiol, or Minovlar. The same dose of oestrogen was common to all three treatment groups. Patients were assessed every 2 months for 6 months, by grading for severity of the acne, lesion counts and photography, and subjectively using a visual analogue scale. In addition, bacteriological sampling and sebum excretion rate (SER) measurements were performed. The results showed a clinical improvement in all three treatment groups, but a more rapid and complete response was seen in those groups who received CPA. There was also a consistent trend suggesting a more favourable response in those in the high dose CPA group. Although there was a marked reduction in SER in the groups treated with CPA, there was no correlation between reduction in SER and clinical improvement in individuals, nor could a reduction in the surface bacterial population be shown to be a primary event in the success of anti-androgen therapy. We have shown that the addition of CPA to oestrogen adds significantly to the therapeutic effect in acne and that anti-androgen and oestrogen combinations are more effective than standard oestrogen and progestagen contraceptive pills.
title: Efficacy of a combined oral contraceptive containing 0.030 mg ethinylestradiol/2 mg dienogest for the treatment of papulopustular acne in comparison with placebo and 0.035 mg ethinylestradiol/2 mg cyproterone acetate.
abstract: Acne is a multifactorial disease characterized by androgenic stimulation of sebaceous glands. Therefore, combined oral contraceptives (COCs) containing anti-androgenic progestogens are suitable candidates for acne treatment. This study aimed to show that a COC containing the anti-androgen dienogest (DNG) is superior to placebo and not inferior to a COC containing the potent anti-androgen cyproterone acetate (CPA) in improving mild to moderate acne.
title: Efficacy and acceptability of two monophasic oral contraceptives containing ethinylestradiol and either desogestrel or gestodene.
abstract: To assess the contraceptive efficacy, cycle control and acceptability of two monophasic oral contraceptives containing either 30 micrograms ethinylestradiol plus 150 micrograms desogestrel or 30 micrograms ethinylestradiol plus 75 micrograms gestodene.
title: Effect of a desogestrel-containing oral contraceptive on the skin.
abstract: This pilot study evaluated the effects of a desogestrel-containing oral contraceptive (DSG-OC) on facial seborrhea (oiliness), acne and related factors in otherwise healthy women with moderate facial acne vulgaris.
title: Effects of cyproterone acetate plus ethinylestradiol low dose on plasma androgens and lipids in mildly hirsute or acneic young women.
abstract: The purpose of this study was to compare, by a randomized double-blind study, involving 30 women with either acne or mild hirsutism, the effects on plasma androgens and lipoproteins, of two hormonal preparations used in acne and ensuring reliable contraception, namely DianeR (cyproterone acetate 2 mg and ethinylestradiol 50 micrograms per pill - D-50) and Diane 35 (cyproterone acetate 2 mg and ethinylestradiol 35 micrograms per pill - D-35). Both drugs, used over a 6-month period (treatment cycle of 21 days with a pill-free interval of 7 days), induced an impressive decrease of free testosterone levels and of 5 alpha-androstane-3 alpha, 17 beta-diol-glucuronide, a parameter of peripheral androgen formation; also dehydroepiandrosterone sulfate levels decreased significantly. Except for an increase of both total T and dihydrotestosterone and as well as for a more important increase in SHBG levels during treatment with D-50, consequences of its more pronounced estrogen dominance in comparison to D-35, the effects of both drugs on androgen levels were similar. The effects on lipids were characterized by a non-significant increase of total cholesterol and a significant increase of HDL-C, HDL2-C and Apo-Al lipoproteins, which were somewhat more pronounced during D-50 treatment. Triglycerides increased significantly during D-50 but hardly during D-35 treatment, whereas HDL-C/LDL-C increased similarly during treatment with either drug. It is concluded that, being as efficient as D-50 in treatment of acne and hirsutism and taking into account its reliable contraceptive effects, without unfavourable effects, as far as atherogenesis is concerned, on plasma lipids, D-35 is to be preferred over D-50.
title: Efficacy and tolerability of a monophasic oral contraceptive containing ethinylestradiol and drospirenone.
abstract: To assess the contraceptive reliability, cycle control and tolerability of a new monophasic oral contraceptive containing 30 g ethinylestradiol plus 3 mg drospirenone (Yasmin, Schering AG, Berlin, Germany), it was compared with an established oral contraceptive containing 30 g ethinylestradiol plus 150 g desogestrel (Marvelon, NV Organon, Oss, The Netherlands).
title: A comparison of the cycle control, safety, and efficacy profile of a 21-day regimen of ethinylestradiol 20mug and drospirenone 3mg with a 21-day regimen of ethinylestradiol 20mug and desogestrel 150mug.
abstract: To compare the cycle control, efficacy, and safety of a new low-dose combined oral contraceptive containing ethinylestradiol 20mug and drospirenone 3mg with an established formulation containing ethinylestradiol 20mug and desogestrel 150mug.
title: Weight change and adverse event incidence with a low-dose oral contraceptive: two randomized, placebo-controlled trials.
abstract: Changes in body weight and the incidence of estrogen-related side effects with low-dose oral contraceptives (OCs) containing 20 microg ethinyl estradiol (EE) have not been demonstrated in placebo-controlled trials. Two placebo-controlled, randomized trials demonstrated the efficacy of a low-dose OC for the treatment of acne in healthy females (n = 704; >or=14 years old) with regular menstrual cycles and moderate facial acne. Patients were randomized to receive 20 microg EE/100 microg levonorgestrel (LNG) or placebo for six cycles. Body weight was measured at baseline and during Cycles 1, 3, and 6. The occurrence of adverse events was recorded at each visit. Mean changes in weight from baseline were similar with 20 microg EE/100 microg LNG [0.72 kg +/- 2.64 (SD; n = 349)] and placebo [0.56 kg +/- 2.64 (SD; n = 355; p > 0.05)] for the last measured weight of each patient. Rates of headache, nausea, weight gain, and breast pain, side effects commonly attributed to OCs, were also similar between groups (p > 0.05). No serious, unexpected, drug-related adverse events occurred during the study. The low-dose OC containing 20 microg EE/100 microg LNG is safe, well tolerated, and does not cause weight gain.
title: An open study of Triphasil and Diane 50 in the treatment of acne.
abstract: Levonorgestrel, as used in oral contraceptives, has antiovulatory activity at doses far lower than those producing androgenic effects. Triphasil, containing levonorgestrel was compared with Diane, containing cyproterone acetate in a trial of acne treatment. Twenty closely matched patients were alternatively allocated to 6 months of Triphasil or Diane treatment. Both groups had a 72% reduction in acne counts. Assays of total testosterone, androgen index, free testosterone, dehydroepiandrosterone sulphate and androstenedione showed significant reduction on treatment and sex hormone binding globulin was raised. All hormonal changes were more marked in the Diane group. Side effects caused only one withdrawal from the trial.
title: [Acne: long-term therapy with side effect. Sebaceous gland activity is androgen dependent--acne therapeutic drug is effective as a contraceptive].
title: Shorter pill-free interval in combined oral contraceptives decreases follicular development.
abstract: The objective of the study was to determine the suppressive effect on ovarian activity of 20 micrograms ethinylestradiol plus 75 micrograms gestodene administered for 21 or 23 days. The study was designed as a double-blind, randomized, multicenter trial in 60 women. A pre-treatment cycle, three treatment cycles and a post-treatment period were monitored by ovarian ultrasound and by LH, FSH, 17 beta-estradiol and progesterone measurements every other day. No ovulation and no luteinized, unruptured follicle were observed. Suppression of ovarian activity was more pronounced by the 23-day regimen. 17 beta-Estradiol serum levels during the last six days of a cycle and during the first six days of the next cycle were significantly less (p < 0.05) in the 23-day regimen. The superiority of the 23-day regimen in comparison to the 21-day regimen with regard to the suppression of ovarian activity was shown in this study. The observed differences in the 17 beta-estradiol levels and follicular development between a 21-day and 23-day preparation combine to suggest that shortening the pill-free interval in combined oral contraceptives may increase the contraceptive safety margin in women on low-dose formulations.
title: Efficacy of an oral contraceptive containing EE 0.03 mg and CMA 2 mg (Belara) in moderate acne resolution: a randomized, double-blind, placebo-controlled Phase III trial.
abstract: The study was conducted to assess the effects of the monophasic combined oral contraceptive containing ethinyl estradiol (EE) 0.03 mg and chlormadinone acetate (CMA) 2 mg (EE/CMA) on papulopustular acne of the face, décolleté (low neck) and back; on moderate comedonal acne of the face; and on seborrhea, alopecia and hirsutism.
title: Effects of oral contraceptives containing ethinylestradiol with either drospirenone or levonorgestrel on various parameters associated with well-being in healthy women: a randomized, single-blind, parallel-group, multicentre study.
abstract: The combined oral contraceptive Yasmin (drospirenone 3 mg plus ethinylestradiol 30 microg [DRSP 3 mg/EE 30 microg]) has been shown to be a well tolerated and effective combination that provides high contraceptive reliability and good cycle control. Furthermore, DRSP 3 mg/EE 30 microg has been shown to have a positive effect on premenstrual symptoms and well-being/health-related quality of life, and to improve the skin condition of women with acne. To date, however, there have been relatively few studies that have compared the effects of DRSP 3 mg/EE 30 microg on the general well-being of women with those of other oral contraceptives.
title: Efficacy and safety of 3 mg drospirenone/20 mcg ethinylestradiol oral contraceptive administered in 24/4 regimen in the treatment of acne vulgaris: a randomized, double-blind, placebo-controlled trial.
abstract: A randomized, double-blind, parallel-group study to investigate the efficacy and safety of the 3 mg drospirenone (drsp)/20 mcg ethinylestradiol (EE) combined oral contraceptive (COC) administered in a 24/4 regimen (24 active tablets and 4 inert tablets per cycle) for the treatment of moderate acne vulgaris.
title: Evaluation of a unique oral contraceptive in the treatment of premenstrual dysphoric disorder.
abstract: Premenstrual dysphoric disorder (PMDD) is a severe form of premenstrual syndrome (PMS). This is the first trial of a unique oral contraceptive containing a combination of drospirenone (DRSP, 3 mg) and ethinyl estradiol (EE, 30 microg) for the treatment of PMDD. DRSP is a spironolactone-like progestin with antiandrogenic and antimineralocorticoid activity. Spironolactone has been shown to be beneficial in PMS, whereas oral contraceptives have shown conflicting results. In this double-blind, placebo-controlled trial, 82 women with PMDD (Diagnostic and Statistical Manual of Mental Disorders, 4th ed. [DSM IV]) were randomized to receive DRSP/EE or placebo for three treatment cycles. The primary end point was change from baseline in luteal phase symptom scores as assessed on the Calendar of Premenstrual Experiences (COPE) scale. Patients treated with DRSP/EE showed a numerically greater change from baseline compared with those treated with placebo on each of the 22 COPE items and each of the 4 symptom factors. Between-group differences in symptom improvement reached statistical significance in factor 3 only (appetite, acne, and food cravings, p = 0.027). The secondary end points, Beck Depression Inventory (BDI) and Profile of Mood States (PMS), were consistent with the primary end point in that patients treated with the oral contraceptive showed a numerically greater improvement from baseline compared with those treated with placebo. The results of this study show a consistent trend in the reduction of symptoms that suggested a beneficial effect of DRSP/EE for the treatment of PMDD, despite limitations of the study design.
title: Cycle control, quality of life and acne with two low-dose oral contraceptives containing 20 microg ethinylestradiol.
abstract: Poor cycle control and tolerability can be reasons for irregular pill intake. This study compared the tolerability of two low-dose oral contraceptives and their effect on cycle control.
title: [The treatment of virilizing syndromes. Comparative clinical studies of 2 antiandrogen-active gestagens (cyproterone acetate, megestrol acetate].
abstract: Treatment of virilization symptoms in 230 patients is reported. 68 patients were treated with Planovin (4 mg megestrol acetate and .05 mg ethinyl estradiol), 77 with SH81041 (100 mg Cyproterone acetate for 10 days and .05 mg ethinyl estradiol for 21 days), and 85 were treated first and Planovin and then with SH81041. Acne, seborrhea, hirsutism, and alopecia improved under treatment with each preparation; results were similar with acne and alopecia, while SH81041 was somewhat more effective than Planovin in treating seborrhea and hirsutism. Therapeutic results obtained during treatment with SH81041 in acne and alopecia are retained during Planovin treatment, but seborrhea and hirsutism become worse again. Successful treatment was independent of the severity of hirsutism and the duration of of treatment. Side effects included breakthrough bleeding and sweating.
title: The effects of CTR-24, a biphasic oral contraceptive combination, compared to Diane-35 in women with acne.
abstract: One-hundred-and-eighty-three women were enrolled in an open, randomized, multicentre study in which the effects on acne of a low-dose biphasic oral contraceptive containing a daily dosage of 25 micrograms desogestrel and 40 micrograms ethinylestradiol (7 days) and a daily dosage of 125 micrograms desogestrel and 30 micrograms ethinylestradiol (15 days) were compared to Diane-35 containing a daily dosage of 2.0 mg cyproterone acetate and 30 micrograms ethinylestradiol (21 days) during four cycles of treatment. Clinical and photographic evaluation of acne plus laboratory assessments were done before treatment and at the end of cycle 4. A reduction with regard to the number of lesions and the degree of severity was observed in both groups. No differences were found between the two treatments in the clinical and photographic evaluation. In both treatment groups, a decrease in total testosterone and 3 alpha-17 beta-androstanediol glucuronide was observed and an increase in SHBG. The decrease in 3 alpha-17 beta-androstanediol was statistically significantly more pronounced in the Diane-35 group.
title: Comparison of two triphasic oral contraceptives containing either gestodene or norethindrone: a randomized, controlled trial.
abstract: Two triphasic oral contraceptives containing either gestodene or norethindrone as the progestogenic compound combined with ethinyl estradiol were compared in a randomized clinical trial to assess their contraceptive reliability, clinical tolerance and cycle control. Both preparations were effective in preventing pregnancy. The gestodene preparation proved significantly superior regarding cycle control and general tolerance.
title: [Therapy of androgenization symptoms: double blind study of an antiandrogen preparation (SH B 209 AB) against neogynon (author's transl)].
abstract: The antiandrogen-containing preparation SH B 209 AB was tested in comparison with an ovulation inhibitor with no antiandrogenic effect (Neogynon) in a randomized, double blind study conducted to determine the effects of both on androgenization symptoms. 88 patients took part in the study. In the majority of cases the duration of the treatment period was more than 6 months. It was shown that the therapy with the combination preparation containing cyproterone acetate was distinctly more successful in cases of acne and seborrhoea: not only acne in its various locations but also all forms of seborrhoea were more favourably influenced by the trial preparation. This difference was statistically significant (p less than 0.05). It was not possible to establish a significant difference between the two preparations in the case of hirsutism in its various locations from the limited number of cases observed. There were also no differences detected in hepatic tolerance. During treatment with both preparations all values measured were within the normal range.
title: Effects of minoxidil 2% vs. cyproterone acetate treatment on female androgenetic alopecia: a controlled, 12-month randomized trial.
abstract: Hormone studies have demonstrated the androgen-dependent character of female androgenetic alopecia, but there have been few controlled studies of therapies for alopecia in women.
title: Cyproterone acetate/ethinyl estradiol in the treatment of acne. A comparative dose-response study of the estrogen component.
abstract: The investigators compared 2 mg cyproterone acetate (CPA) in combination with either 0.035 mg or 0.050 mg ethinyl estradiol (EE2) (Diane -35 versus Diane -50) in the treatment of acne. Both formulations of Diane were highly effective in improving acne, even in women who had been refractory to other types of medication. Cycle control with both formulations was excellent and adverse effects were generally mild and confined to the first two cycles of treatment. Mean plasma lipid levels increased with both treatments, yet most individual values remained within normal limits after one year of therapy while the LDL-cholesterol/HDL-cholesterol ratio was stable throughout the study period. Plasma testosterone and DHEA-S levels paralleled the decline in the clinical severity of the acne. There was no loss of clinical effectiveness with Diane -35 and it provided the advantage of a 30% decrease in the amount of estrogen.
title: The CONSORT statement: revised recommendations for improving the quality of reports of parallel-group randomised trials.
abstract: To comprehend the results of a randomised controlled trial (RCT), readers must understand its design, conduct, analysis, and interpretation. That goal can be achieved only through total transparency from authors. Despite several decades of educational efforts, the reporting of RCTs needs improvement. Investigators and editors developed the original CONSORT (Consolidated Standards of Reporting Trials) statement to help authors improve reporting by use of a checklist and flow diagram. The revised CONSORT statement presented here incorporates new evidence and addresses some criticisms of the original statement. The checklist items pertain to the content of the Title, Abstract, Introduction, Methods, Results, and Discussion. The revised checklist includes 22 items selected because empirical evidence indicates that not reporting this information is associated with biased estimates of treatment effect, or because the information is essential to judge the reliability or relevance of the findings. We intended the flow diagram to depict the passage of participants through an RCT. The revised flow diagram depicts information from four stages of a trial (enrollment, intervention allocation, follow- up, and analysis). The diagram explicitly shows the number of participants, for each intervention group, included in the primary data analysis. Inclusion of these numbers allows the reader to judge whether the authors have done an intention- to-treat analysis. In sum, the CONSORT statement is intended to improve the reporting of an RCT, enabling readers to understand a trial's conduct and to assess the validity of its results.