Cyproterone acetate as initial treatment and maintenance therapy for hirsutism

1985 ◽  
Vol 109 (4) ◽  
pp. 522-529 ◽  
Author(s):  
I. M. Holdaway ◽  
M. S. Croxson ◽  
H. K. Ibbertson ◽  
A. Sheehan ◽  
B. Knox ◽  
...  
Keyword(s):  
Growth Rate ◽  
Side Effects ◽  
Maintenance Therapy ◽  
Cyproterone Acetate ◽  
Hair Growth ◽  
Low Dose ◽  
Sex Hormone Binding Globulin ◽  
Plasma Testosterone ◽  
High Dose ◽  
Dose Therapy

Abstract. Thirty-four patients with hirsutism were treated for 9 months with 100 mg cyproterone acetate (CA) given on days 5–15 of the menstrual cycle together with a combination oral contraceptive containing 2 mg CA and 50 μg ethinyloestradiol (Diane®) given on days 5–25 of the cycle. After 9 months treatment patients were randomised to a 12 month double-blind cross-over trial comparing Diane® plus 25 mg CA with Diane® plus placebo, to test the efficacy of low-dose CA as maintenance therapy. Thirty-one patients (92%) experienced moderate or good subjective improvement in hirsutism on high-dose CA, associated with a 40% mean overall improvement in objective hirsutism grade and 13% overall reduction in hair growth rate measured by a photographic technique. Minor or moderate side effects were experienced by 64% of patients and severe side effects by 11% at this dosage. There was a mean subjective relapse rate of 33% when patients were changed to low dose CA, and relapse rates were not significantly different between the two regimens with 28% relapsing on 25 mg CA + Diane® and 48% on placebo and Diane® (P < 0.05). Despite significant subjective relapse with low-dose treatment there was no significant deterioration in objective hirsutism grade or hair growth rate determined photographically. Levels of plasma testosterone, sex hormone binding globulin, free testosterone (derived) and androstenedione fell significantly on high dose CA and this reduction was maintained during low dose therapy. Cyproterone acetate at high dosage thus appeared an effective agent in the treatment of hirsutism, but 33% of patients considered they deteriorated when changed to low-dose therapy despite maintenance of androgen suppression and lack of change in objective measurements. Maintenance therapy after remission with high-dose CA appears justified since 60% of patients underwent subjective relapse when all treatment was stopped.

scholarly journals A Prospective Randomized Trial Comparing Low Dose Flutamide, Finasteride, Ketoconazole, and Cyproterone Acetate-Estrogen Regimens in the Treatment of Hirsutism

1999 ◽  
Vol 84 (4) ◽  
pp. 1304-1310 ◽  
Author(s):  
S. Venturoli ◽  
O. Marescalchi ◽  
F. M. Colombo ◽  
S. Macrelli ◽  
B. Ravaioli ◽  
...  
Keyword(s):  
Growth Rate ◽  
Side Effects ◽  
Cyproterone Acetate ◽  
Hair Growth ◽  
Ethinyl Estradiol ◽  
Dehydroepiandrosterone Sulfate ◽  
Sex Hormone Binding Globulin ◽  
Low Doses ◽  
Significant Difference ◽  
Hair Diameter

Sixty-six hirsute women were randomized and treated with 1) flutamide (n = 15), 250 mg/day; 2) finasteride (n = 15), 5 mg/day; 3) ketoconazole (n = 16), 300 mg/day; and 4) ethinyl estradiol (EE)-cyproterone acetate (CPA; n = 20), 0.01 mg EE/day for the first week, 0.02 mg EE/day for the second week, and 0.01 mg EE/day for the third week, followed by a pause of 7 days, then 12.5 mg CPA/day added during the first 10 days of every month for 12 months. Hirsutism was evaluated by the Ferriman-Gallwey score, and hair diameter and hair growth rate were determined by a special image analysis processor in basal conditions and after 90, 180, 270, and 360 days of treatment. All treatments produced a significant decrease in the hirsutism score, hair diameter, and daily hair growth rate: flutamide, −55 ± 13%, −21 ± 14%, and −37 ± 18%; finasteride, −44 ± 13%, −16 ± 12%, and− 27 ± 14%; ketoconazole, −53 ± 18%, −14 ± 12%, and −30 ± 21%; and EE-CPA, −60 ± 18%, −20 ± 11%, and −28 ± 21%. Some differences existed among treatments with regard to effectiveness; EE-CPA and flutamide seem to be the most efficacious in improving hirsutism. For the hirsutism score, a greater decrease was seen with EE-CPA (−60 ± 18%) than with finasteride (−44 ± 13%; P &lt; 0.01) and a greater decrease was seen with flutamide (−58 ± 18%) than with finasteride (−44 ± 13%; P &lt; 0.05). Flutamide is the fastest in decreasing hair diameter; EE-CPA is the fastest in slowing down hair growth, even though at the end of the treatment there was a significant difference between flutamide and finasteride only (−41 ± 18% vs.− 27 ± 14%; P &lt; 0.05). Flutamide, ketoconazole, and EE-CPA induced a significant decrease in total and free testosterone, 5α-dihydrotestosterone, dehydroepiandrosterone, dehydroepiandrosterone sulfate, and androstenedione plasma levels. During the EE-CPA treatment, gonadotropins were suppressed, and the sex hormone-binding globulin level increased. Finasteride induced a decrease in dehydroepiandrosterone sulfate and 5α-dihydrotestosterone and an increase in testosterone levels. Very few side-effects were observed during treatment with low doses of flutamide, EE-CPA, and particularly finasteride. Flutamide induced a decrease whereas EE-CPA induced an increase in triglycerides and cholesterol, showing higher values within the normal range. Ketoconazole induced several side-effects and complications, and several people dropped out of the study. Despite different modalities of action and significantly different effects on androgen levels, low doses of flutamide, finasteride, and EE-CPA constitute very satisfactory alternative therapeutic regimens in the treatment of hirsutism.

Hair growth and androgen responses in hirsute women treated with continuous cyproterone acetate and cyclical ethinyl oestradiol

1987 ◽  
Vol 116 (4) ◽  
pp. 497-501 ◽  
Author(s):  
D. B. Jones ◽  
I. Ibraham ◽  
C. R. W. Edwards
Keyword(s):  
Growth Rate ◽  
Cyproterone Acetate ◽  
Hair Growth ◽  
Free Testosterone ◽  
Sex Hormone Binding Globulin ◽  
Plasma Testosterone ◽  
Skin Area ◽  
Total Plasma ◽  
Hair Density ◽  
Ethinyl Oestradiol

Abstract. Eighteen hirsute women (8 with polycystic ovarian syndrome, 10 with idiopathic hirsutism) were treated for up to 12 months with cyproterone acetate, 150 mg daily, and ethinyl oestradiol, 50 μg on days 5–25 of the menstrual cycle. Hair growth rate and density were measured from standardized serial photographs of a shaved skin area. A significant reduction was seen in mean hair growth rate, total plasma testosterone, free testosterone index, plasma dehydroepiandrosterone, and plasma androstenedione. LH and FSH also fell and sex hormone binding globulin level increased. No significant changes occurred in hair density or in serum PRL levels. A significant correlation was observed between hair growth rate and total plasma testosterone for the pooled results (r = 0.35, P < 0.005). No significant correlations were seen between hair density and the endocrine parameters studied.

Adjuvant Vaginal High-Dose-Rate Afterloading Alone in Endometrial Carcinoma: Patterns of Relapse and Side Effects Following Low-Dose Therapy

1998 ◽  
Vol 71 (1) ◽  
pp. 72-76 ◽  
Author(s):  
Elisabeth Weiss ◽  
Peter Hirnle ◽  
Heike Arnold-Bofinger ◽  
Clemens F. Hess ◽  
Michael Bamberg
Keyword(s):  
Side Effects ◽  
Endometrial Carcinoma ◽  
Dose Rate ◽  
Low Dose ◽  
High Dose Rate ◽  
High Dose ◽  
Dose Therapy

ENDOCRINE CHANGES IN MALE SEXUAL DEVIANTS AFTER TREATMENT WITH ANTI-ANDROGENS, OESTROGENS OR TRANQUILLIZERS

1975 ◽  
Vol 67 (2) ◽  
pp. 179-188 ◽  
Author(s):  
M. A. F. MURRAY ◽  
J. H. J. BANCROFT ◽  
D. C. ANDERSON ◽  
T. G. TENNENT ◽  
P. J. CARR
Keyword(s):  
Sexual Offenders ◽  
Cyproterone Acetate ◽  
Follicle Stimulating Hormone ◽  
Sex Hormone Binding Globulin ◽  
Plasma Testosterone ◽  
Total Plasma ◽  
Hormone Binding ◽  
Endocrine Effects ◽  
Threefold Increase ◽  
Special Hospital

SUMMARY The endocrine effects of drugs on two groups of 12 male sexual offenders in a special hospital were studied. In the first study benperidol, chlorpromazine and placebo were compared and in the second ethynyl oestradiol and cyproterone acetate were compared with no treatment. In the first study there was no difference between the three drugs in their effects on plasma testosterone or luteinizing hormone (LH). In the second study cyproterone acetate produced a reduction in plasma testosterone, LH and follicle-stimulating hormone (FSH). Ethynyl oestradiol produced a rise in plasma testosterone and LH, and no change in FSH. Neither drug changed total plasma oestrogen levels. The unexpected effects of ethynyl oestradiol were attributed to an increase in sex hormone-binding globulin (SHBG) leading to a rise in bound, inactive testosterone. Direct measurement showed a two- to threefold increase in SHBG with ethynyl oestradiol treatment and no change in SHBG with cyproterone acetate treatment. In spite of these contrasting endocrine effects, ethynyl oestradiol, cyproterone acetate and benperidol produced similar behavioural changes.

scholarly journals SUN-042 Low Dose Cyproterone Acetate for the Treatment of Transgender Women - a Retrospective Study

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Naomi Even-Zohar ◽  
Yael Sofer ◽  
Iris Yaish ◽  
Merav Serebro ◽  
Karen Tordjman ◽  
...  
Keyword(s):  
Cyproterone Acetate ◽  
Dose Group ◽  
Low Dose ◽  
Dose Range ◽  
Hormonal Treatment ◽  
Transgender Women ◽  
High Dose ◽  
Historical Cohort ◽  
Treatment Groups ◽  
First Time

Abstract Introduction : Transgender women with intact gonads receive lifelong hormonal treatment in order to suppress physiologic androgen production. Cyproterone acetate (CA) is the most comon antiandrogenic drug prescribed for this indication in Europe, with a dose range between 25-100 mg/day. Aim: To assess the effectiveness and safety of low dose (&lt;20 mg/day), compared with high dose (&gt;50 mg/day) CA treatment. Methods: Historical cohort study of transgender women treated in our department between January 2000 and October 2018. Results: There were 42 transgender women in the low dose group (LDG) and 32 in the high dose group (HDG). Age (27.9 ± 1.6 vs.28.9 ± 1.7 years) and follow up time (16.2 ± 2.2 vs. 20.1 ± 2.1 months) were similar in the LDG and HDG, respectively. At the last available visit, testosterone levels were effectively and similarly suppressed in both treatment groups (0.6 ± 0.1 vs 0.8 ± 0.3 nmol/l; p=0.37, for LDG and HDG respectively). Prolactin (659 ± 64 vs 486 ± 42 mIU/ml, p=0.02), LDL cholesterol (96.1 ± 5 vs 78.5 ± 4 mg/dl, p= 0.02) and triglycerides (93.3 ± 9 vs 69 ± 5 mg/dl; p=0.02) were higher in the HDG compared with LDG respectively. Side effects were common in the HDG (four cases of increased liver enzymes, one case of pulmonary embolism and one case of sudden death). Conclusion: We show for the first time that anti-androgenic treatment of transgender women with low dose CA is as effective as high dose treatment, but safer. We suggest incorporation of this observation in future guidelines.

6081Efficacy and limitations of quinidine therapy in patients with Brugada Syndrome

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
A Mazzanti ◽  
E Tenuta ◽  
M Marino ◽  
E Pagan ◽  
M Morini ◽  
...  
Keyword(s):  
Cardiac Arrest ◽  
Side Effects ◽  
High Risk ◽  
Brugada Syndrome ◽  
Low Dose ◽  
Clinical Course ◽  
High Risk Group ◽  
High Dose ◽  
Life Threatening ◽  
Patients Experience

Abstract Background Quinidine at high-dose is used in patients with Brugada Syndrome (BrS), but its efficacy to prevent life-threatening arrhythmic events (LAE) in BrS is unproven and its use is limited by side effects. Objective We assessed whether low-dose quinidine in BrS patients reduces: 1) the occurrence of a first LAE; 2) the arrhythmic burden in the high-risk group of cardiac arrest survivors. Methods We first compared the clinical course of 53 BrS patients treated with quinidine to that of 441 untreated controls, matched by sex, age, and symptoms. Furthermore, we calculated the annual incidence of LAEs off- and on-quinidine in 123 BrS patients who had survived a cardiac arrest. Results First, we compared the clinical course of 53 BrS patients treated with quinidine (i.e. “cases”: 89% males, median age 40 years) to that of 441 untreated, clinically-matched BrS patients (i.e. “controls”: 91% males, median age 41 years) present in our database of patients with inherited arrhythmias. Cases received quinidine (median dose of 450 mg per day) for 5.0±3.7 years. Quinidine was interrupted in only 3/53 cases (6%) for side effects and it conferred a nonsignificant reduction of the risk of a first LAE in cases versus controls (HR 0.74, 95% CI 0.22–2.48, P=0.62). Secondly, we calculated the annual recurrence of LAE off- and on-quinidine in 123 BrS cardiac arrest survivors, 27 of whom were treated with quinidine for 7.0±3.5 years. The annual rate of recurrent LAEs decreased significantly from 14.7% while off-quinidine to 3.9% while on-quinidine (P=0.03). Notably, recurrent life-threatening arrhythmic events were recorded in 4/27 (15%) symptomatic patients while on-quinidine. Conclusion We demonstrated for the first time in the long-term that low-dose quinidine reduces the recurrence of life-threatening arrhythmias in symptomatic BrS patients, with few side effects. Remarkably, about one-fifth of symptomatic patients experience life-threatening arrhythmias while on-treatment, suggesting that quinidine cannot replace implantable defibrillators in high-risk subjects.

scholarly journals Efficacy of NS-718, a Novel Lipid Nanosphere-Encapsulated Amphotericin B, againstCryptococcus neoformans

1998 ◽  
Vol 42 (7) ◽  
pp. 1722-1725 ◽  
Author(s):  
Mohammad Ashraf Hossain ◽  
Shigefumi Maesaki ◽  
Hiroshi Kakeya ◽  
Tetsuhiro Noda ◽  
Katsunori Yanagihara ◽  
...  
Keyword(s):  
Amphotericin B ◽  
Antifungal Agent ◽  
Low Dose ◽  
Yeast Cells ◽  
High Dose ◽  
Pulmonary Cryptococcosis ◽  
High Dose Therapy ◽  
Dose Therapy

ABSTRACT In vitro and in vivo efficacies of NS-718, a lipid nanosphere-encapsulated amphotericin B (AMPH-B), have been studied. Of the tested AMPH-B formulations, NS-718 had the lowest MIC forCryptococcus neoformans. In a murine model, low-dose therapy (0.8 mg/kg of body weight) with NS-718 showed higher efficacy than that with AmBisome. High-dose therapy (2.0 mg/kg) with NS-718 was much more effective than those with Fungizone and AmBisome. In mice treated with a high dose of NS-718, only a few yeast cells had grown in lung by 7 days after inoculation. A pharmacokinetic study showed higher concentrations of AMPH-B in lung following administration of NS-718 than after administration of AmBisome. Our results indicated that NS-718, a new AMPH-B formulation, is a promising antifungal agent for treatment of pulmonary cryptococcosis and could be the most effective antifungal agent against C. neoformans infections.

Low-dose versus high-dose therapy for Gaucher disease: goals and markers

Blood ◽  
2007 ◽  
Vol 109 (1) ◽  
pp. 387-387 ◽  
Author(s):  
Carla E. M. Hollak ◽  
Maaike de Fost ◽  
Johannes M. F. G. Aerts ◽  
Stephan vom Dahl
Keyword(s):  
Gaucher Disease ◽  
Low Dose ◽  
High Dose ◽  
High Dose Therapy ◽  
Dose Therapy

Imatinib and Interferon-Alpha Maintenance Therapy for Patients with Philadelphia-Positive Acute Lymphoblastic Leukemia (Ph+ALL) Ineligible for Allogeneic Stem Cell Transplantation (SCT).

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2042-2042
Author(s):  
Heike Pfeifer ◽  
Barbara Wassmann ◽  
Andreas Käbisch ◽  
Michael Lübbert ◽  
Lothar Leimer ◽  
...  
Keyword(s):  
Side Effects ◽  
Elderly Patients ◽  
Maintenance Therapy ◽  
Low Dose ◽  
Front Line ◽  
Consolidation Chemotherapy ◽  
Mutation Status ◽  
Line Therapy ◽  
Remission Duration

Abstract Abstract 2042 Poster Board II-19 Introduction: The tyrosine kinase inhibitor imatinib (IM), alone or in combination with chemotherapy, has become the mainstay of front-line treatment for Ph+ ALL. We recently demonstrated that IM in combination with intensive consolidation chemotherapy of approximately one year duration is feasible in elderly patients with de novo Ph+ ALL, but is associated with a high relapse rate. Allogeneic SCT (alloSCT) is potentially curative but may not be feasible in most elderly or comorbid patients. Maintenance therapy (MT) in such patients is conceptually attractive, but data on whether any type of MT facilitates long-term leukemia-free survival of patients with Ph+ALL in first CR is lacking. Based on data suggesting that interferon-alpha (IFN-a) possesses anti-leukemic activity in patients with Ph+ALL, we conducted a phase II study to determine the feasibility and efficacy of MT consisting of imatinib in combination with low-dose (LD) IFN-a in elderly patients with Ph+ALL who were not eligible for SCT. In addition, we examined whether bcr-abl transcript levels and mutation status were predictive of relapse and remission duration. Methods: Nineteen elderly patients (median age 66 yrs; [60-75 yrs.]) who had received IM-based remission induction and consolidation therapy as reported previously (Ottmann et al., Cancer 109:2068-76, 2007) were enrolled in a clinical trial of IM 400 mg daily in combination with LD-IFNa with a target dose of 3 Mio IU/week. At the time of enrollment, the majority of patients (n=12) had received five (n=3) or six (n=9) consolidation cycles, the remaining patients had discontinued intensive front-line therapy after four (n=2), three (n=1), two (n=1), and one (n=1) consolidation cycles, 2 patients were switched to MT after induction. The median number of cycles of consolidation chemotherapy given concurrently with IM was six. Minimal residual disease (MRD) was serially assessed by quantitative RT-PCR, mutational analyses was performed by D-HPLC and direct sequencing. Results: The median overall duration of MT is 26 mos. (range 3-92 mos.). Seven of 19 pts. (37 %) are in ongoing CR, with a median remission duration from start of maintenance of 76.7 mos. (54-91 mos.). Median overall survival of all pts. is 61 mos. (range: 20-99 mos.). Eleven of 18 evaluable pts. experienced side effects which lead to a dose reduction of IFN. 9 pts. suffered from moderate depressions or fatigue. Hematologic toxicity was mild: only 2 pts. developed grade 3 cytopenia during MT. Remission duration was independent of the number of previous cycles of intensive chemotherapy, of the MRD response during the first 6 mos. of intensive front-line therapy (16 mos. vs. 26 mos.) and of achievement of PCR negativity at any time during intial therapy. Surprisingly, the bcr-abl transcript level at the start of MT likewise had no impact on time to disease recurrence. Conclusions: In elderly Ph+ALL pts. ineligible for allogeneic SCT, maintenance with imatinib in combination with low-dose IFN-a results in long-term sustained remissions in a substantial proportion of patients, with acceptable side effects. Surprisingly, the MRD response and mutation status prior to MT were not significantly predictive of remission duration. Likewise, greater intensity of prior chemotherapy as determined by the number of administered consolidation cycles had no significant benefit with respect to remission duration during MT. More extensive evaluation of tyrosine kinase inhibitors in combination with LD IFNa as MT for Ph+ALL is warrented. Disclosures: Ottmann: Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; BMS: Honoraria.

Maintenance Low Dose 13 Cis-Retinoic Acid and Alpha Tocopherol Improves Survival Compared to High Dose Therapy for 6 Months In LOW and INT-1/2 Stage MDS: Role for Prevention Trial

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 5053-5053
Author(s):  
Emmanuel C. Besa ◽  
Joseph Vadakara
Keyword(s):  
Retinoic Acid ◽  
Retrospective Study ◽  
Side Effects ◽  
Low Dose ◽  
Low Risk ◽  
Alpha Tocopherol ◽  
High Dose ◽  
Off Label ◽  
Stage Disease

Abstract Abstract 5053 There are no current therapies or preventative strategies other than transfusion support and possibly growth factor support for the management of low risk and INT 1 Myelodysplasia. There have been a few studies that looked into the effect of 13 cis-retinoic acid (13CRA) by itself and in combination with other drugs that showed some benefits to the use of 13CRA in MDS. A randomized blinded study failed to show any benefit of 13CRA over placebo; however in this study many of the patients discontinued therapy due to side effects of the 13CRA and significant number of the patients had advanced stage disease and either had CMML, RAEB, and RAEB-t based on the classification in use then. Other studies have suggested that the beneficial effect of 13CRA is possibly seen in early stage disease and in low risk Refractory Anemia patients. To look into the benefit that 13CRA might have on IPSS low risk, INT-1 and INT-2 MDS patients we conducted a retrospective study that looked at the effect of 13CRA given in two different doses and durations. Methods: This was a retrospective study that looked at patients with IPSS low risk and INT-1 and INT-2. The patients were divided into two groups. One group was treated with a dose of 13CRA at a dose of 100mg/m2/day for 6 months. The second cohort was treated with a dose of 40mg of 13CRA until disease progression. Disease progression was then compared in the two groups to see if there was any statistical difference in the treatment arms. One of the patients did not seem to have any side effects of 13CRA and it was later found that that patient was on alpha tocopherol, once this was realized then all the patients were given Alpha tocopherol (AT) at a dose 800mg per day along with 13CRA. Results: Twenty patients were identified in the high dose short term arm, and 29 patients in the low dose long term arm. Both groups were similar in age (mean, range) in years, male/female ratio, duration from diagnosis to treatment. IPSS scores and transfusion requirements were comparable. Responses were observed in both groups with an overall response rate of 44.8% in HDST and 75% in LDLT with similar, low AML transformation in INT-1-2 patients of 15% in LDLT and 13.7% in HDST. A better median survival was observed with 5 patients still alive at 72 months in LDLT compared to 30 months in HDST group with a difference of 42 months (3.5 years) (Log-rank p value= 0.0099). The patients who were on the LDLT arm with alpha tocopherol had a much better toxicity profile with only 5% developing skin toxicity compared to as high as 27% in HDST arm and 100% in patients who only received 13CRA, similarly triglyceride changes were seen in 5%, 20%, and 52% respectively, AST elevations were seen in 0%, 2% and 19 % respectively. This suggest that lack of toxicity and good tolerance using 13 CRA at 40 mg/d with 800 mg of AT for long term preventive measure in early phase MDS may result in prolonged survival and may be used as basis for a prospective prevention trial. Disclosures: Off Label Use: 13 cis retinoic acid is used off label.

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