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American Journal of Clinical Dermatology Sep 2011Acne vulgaris, hirsutism, seborrhea and female pattern hair loss (FPHL) are common disorders of the pilosebaceous unit (PSU). In some women with hyperandrogenemia, an... (Review)
Review
Acne vulgaris, hirsutism, seborrhea and female pattern hair loss (FPHL) are common disorders of the pilosebaceous unit (PSU). In some women with hyperandrogenemia, an excess of androgens at the PSU can lead to the development of these dermatological manifestations. These manifestations can cause many psychiatric and psychological implications, such as social fears and anxiety, and can adversely affect quality of life. High androgen levels at the PSU as a possible underlying cause of acne vulgaris, hirsutism, seborrhea and FPHL supports the rationale for using combined oral contraceptives for the management of these conditions in women. The purpose of this review is to describe these dermatological manifestations of the PSU and the management of these conditions through the use of the oral contraceptive ethinylestradiol/chlormadinone acetate (EE/CMA). EE/CMA 0.03/2 mg is a combined monophasic contraceptive pill with anti-androgenic properties. It is approved in Europe for contraception and has been investigated in phase III trials for the treatment of acne. EE/CMA was better than placebo and similar to another low-dose oral contraceptive (ethinylestradiol/levonorgestrel) in improving symptoms of acne in two phase III randomized controlled trials in patients with mild to moderate papulopustular acne. In addition, in trials investigating the contraceptive efficacy of EE/CMA, limited data suggest that there were also improvements in hirsutism, FPHL and seborrhea in small subgroups of patients. EE/CMA has a good safety profile. The most commonly reported adverse events are breast tenderness/pain, headache/migraine and nausea. Evidence in the literature indicates that the use of EE/CMA for the treatment of dermatological disorders under the control of androgens may be a valid treatment option. Further investigation is warranted.
Topics: Androgens; Chlormadinone Acetate; Contraceptives, Oral, Combined; Ethinyl Estradiol; Female; Hair Follicle; Humans; Quality of Life; Sebaceous Glands; Skin Diseases
PubMed: 21895044
DOI: 10.2165/1153874-S0-000000000-00000 -
European Journal of Neurology Sep 2022A dose-dependent association between the use of cyproterone acetate (CPA) and intracranial meningioma has been identified but data for other potent progestogens are...
BACKGROUND AND PURPOSE
A dose-dependent association between the use of cyproterone acetate (CPA) and intracranial meningioma has been identified but data for other potent progestogens are scarce. The association was assessed between intracranial meningioma surgery and exposure to three potent progestogens: CPA (≥25 mg/day), nomegestrol acetate (NOMAC) (3.75-5 mg/day) and chlormadinone acetate (CMA) (2-10 mg/day).
METHODS
In this nationwide population-based case-control study, cases underwent surgery for intracranial meningioma in France from 2009 to 2018. They were matched to five control subjects for sex, year of birth and area of residence. Progestogen exposure was defined as progestogen use within the year before surgery for cases or the same date for their controls.
RESULTS
In total, 25,216 cases were included (75% women, median age 58 years). Progestogen exposure was noted for 9.9% of cases (2497/25,216) and 1.9% (2382/126,080) of controls, with an odds ratio (OR) of 6.7 (95% confidence interval [CI] 6.3-7.1). The OR was 1.2 (1.0-1.4) for short-term use (<1 year) and 9.5 (8.8-10.2) for prolonged use. A strong association was identified for prolonged use of CPA (OR = 22.7, 95% CI 19.5-26.4), NOMAC (OR = 6.5, 95% CI 5.8-7.2) and CMA (OR = 4.7, 95% CI 4.5-5.3). Progestogen exposure increased the risk of meningioma for all histological grades and anatomical sites, particularly for the anterior and middle skull base: OR = 35.7 (95% CI 26.5-48.2) and 23.9 (95% CI 17.8-32.2) for CPA. The estimated number of attributable cases was 2124 (95% CI 2028-2220) (212/year).
CONCLUSION
A strong association between prolonged exposure to potent progestogens and surgery for meningioma was observed. The risk increased from CMA to NOMAC to CPA. Individuals should be informed of this risk.
Topics: Case-Control Studies; Cyproterone Acetate; Female; Humans; Male; Meningeal Neoplasms; Meningioma; Middle Aged; Progestins
PubMed: 35621369
DOI: 10.1111/ene.15423 -
BMJ (Clinical Research Ed.) Mar 2024To assess the risk of intracranial meningioma associated with the use of selected progestogens.
OBJECTIVE
To assess the risk of intracranial meningioma associated with the use of selected progestogens.
DESIGN
National case-control study.
SETTING
French National Health Data System (ie, ).
PARTICIPANTS
Of 108 366 women overall, 18 061 women living in France who had intracranial surgery for meningioma between 1 January 2009 and 31 December 2018 (restricted inclusion periods for intrauterine systems) were deemed to be in the case group. Each case was matched to five controls for year of birth and area of residence (90 305 controls).
MAIN OUTCOME MEASURES
Selected progestogens were used: progesterone, hydroxyprogesterone, dydrogesterone, medrogestone, medroxyprogesterone acetate, promegestone, dienogest, and intrauterine levonorgestrel. For each progestogen, use was defined by at least one dispensation within the year before the index date (within three years for 13.5 mg levonorgestrel intrauterine systems and five years for 52 mg). Conditional logistic regression was used to calculate odds ratio for each progestogen meningioma association.
RESULTS
Mean age was 57.6 years (standard deviation 12.8). Analyses showed excess risk of meningioma with use of medrogestone (42 exposed cases/18 061 cases (0.2%) 79 exposed controls/90 305 controls (0.1%), odds ratio 3.49 (95% confidence interval 2.38 to 5.10)), medroxyprogesterone acetate (injectable, 9/18 061 (0.05%) 11/90 305 (0.01%), 5.55 (2.27 to 13.56)), and promegestone (83/18 061 (0.5%) 225/90 305 (0.2 %), 2.39 (1.85 to 3.09)). This excess risk was driven by prolonged use (≥one year). Results showed no excess risk of intracranial meningioma for progesterone, dydrogesterone, or levonorgestrel intrauterine systems. No conclusions could be drawn concerning dienogest or hydroxyprogesterone because of the small number of individuals who received these drugs. A highly increased risk of meningioma was observed for cyproterone acetate (891/18 061 (4.9%) 256/90 305 (0.3%), odds ratio 19.21 (95% confidence interval 16.61 to 22.22)), nomegestrol acetate (925/18 061 (5.1%) 1121/90 305 (1.2%), 4.93 (4.50 to 5.41)), and chlormadinone acetate (628/18 061 (3.5%) 946/90 305 (1.0%), 3.87 (3.48 to 4.30)), which were used as positive controls for use.
CONCLUSIONS
Prolonged use of medrogestone, medroxyprogesterone acetate, and promegestone was found to increase the risk of intracranial meningioma. The increased risk associated with the use of injectable medroxyprogesterone acetate, a widely used contraceptive, and the safety of levonorgestrel intrauterine systems are important new findings.
Topics: Female; Humans; Middle Aged; Progestins; Progesterone; Levonorgestrel; Meningioma; Medroxyprogesterone Acetate; Dydrogesterone; Medrogestone; Promegestone; Case-Control Studies; Meningeal Neoplasms
PubMed: 38537944
DOI: 10.1136/bmj-2023-078078 -
Reproductive Medicine and Biology Jul 2019The clinical utility of chlormadinone acetate tablets (Lutoral™), an orally active progestin which has been available since June 2007, was compared to an in-house...
PURPOSE
The clinical utility of chlormadinone acetate tablets (Lutoral™), an orally active progestin which has been available since June 2007, was compared to an in-house vaginal suppository formulation of progesterone used between 2006 and 2007 for assisted reproductive technology (ART).
METHODS
We retrospectively evaluated the efficacy and safety of chlormadinone acetate by comparing the pregnancy rates and the incidences of birth defects and hypospadias in frozen-thawed embryo transfer cycles using the in-house vaginal progesterone and those using chlormadinone acetate for luteal phase support.
RESULTS
The pregnancy rates in the frozen-thawed embryo transfer cycles were 31.2% (259/831) with vaginal progesterone for luteal phase support and 31.6% (4228/13 381) with chlormadinone acetate (no significant difference). In the cycles resulting in live birth following administration of chlormadinone acetate between July 2007 and December 2015, the incidence of birth defects was 2.8% (80/2893), and the incidence of hypospadias was 0.03% (1/2893).
CONCLUSIONS
These results indicate that the pregnancy rate following frozen-thawed embryo transfer using chlormadinone acetate for luteal phase support was comparable with that using vaginal progesterone, with no increased risk of birth defects, including hypospadias, which has been a concern following the use of progestins.
PubMed: 31312109
DOI: 10.1002/rmb2.12274 -
Journal of Endocrinological... Apr 2020Polycystic ovary syndrome (PCOS) is a common endocrine disorder affecting 5-10% of women of reproductive age. It is characterized by chronic anovulation leading to... (Comparative Study)
Comparative Study
INTRODUCTION
Polycystic ovary syndrome (PCOS) is a common endocrine disorder affecting 5-10% of women of reproductive age. It is characterized by chronic anovulation leading to menstrual disorders, and increased infertility. The syndrome can also manifest as hirsutism and acne.
AIM OF THE STUDY
The aim of the study was to compare, over a duration of 6 months, the effects of drospirenone (DRSP) versus chlormadinone acetate (CMA) containing oral contraceptives (OCs) on clinical, hormonal, and metabolic parameters in 120 PCOS women.
MATERIALS AND METHODS
120 women with the diagnosis of PCOS according to the Rotterdam 2003 criteria were recruited to the study. All patients were divided to two treatment groups of OCs, containing: 3 mg DRSP/30 mcg EE (ethinylestradiol) (60 patients) and 2 mg CMA/30 mcg EE (60 patients). Clinical parameters such as hirsutismus and acne were evaluated. Metabolic parameters such as serum insulin, glucose concentration, homeostatic model assessment of insulin resistance, body mass index, systolic and diastolic blood pressures were also measured. Among hormonal parameters, serum estradiol, luteinizing hormone, follicle-stimulating hormone, prolactin, testosterone, dehydroepiandrosterone sulfate, thyroid-stimulating hormone, and free thyroxine were measured.
RESULTS
The use of both DRSP- or CMA-containing OCs provided similar positive therapeutic effects with regard to clinical, metabolic, and hormonal parameters. Among clinical parameters, like hirsutismus, after 6 months of continuous OC treatment, a statistically significant improvement was observed in both groups: DRSP (p < 0.0001) and CMA OC treatment (p < 0.0001). In addition, significant improvement was showed according to acne lesions both after DRSP (p < 0.0001) and CMA treatments (p < 0.0001). Among glucose, insulin levels and HOMA-IR, there were statistically significant higher levels in both groups after DRSP (p < 0.0001, p < 0.0001, p < 0.05) and CMA OC treatment (p < 0.02, p < 0.0001, p < 0.0001). Hormonal parameters such as LH, FSH, prolactin, testosterone and DHEA-S were statistically significant lower in both groups after DRSP (p < 0.0001, p < 0.0001, p < 0.01, p < 0,002, and p < 0.0001) and CMA OC treatment (p < 0.0001, p < 0.0001, p < 0.04, p < 0.002, and p < 0.0001).
CONCLUSIONS
Further research, however, is needed not only to define optimal duration, and to clarify the effects of treatment on long-term metabolic outcomes, but also to explore different treatment options and possible combined therapies.
Topics: Adult; Androstenes; Blood Glucose; Chlormadinone Acetate; Contraceptives, Oral, Combined; Estradiol; Female; Follicle Stimulating Hormone; Humans; Insulin; Insulin Resistance; Luteinizing Hormone; Polycystic Ovary Syndrome; Testosterone; Young Adult
PubMed: 31654312
DOI: 10.1007/s40618-019-01133-3 -
British Medical Journal Dec 1969
Topics: Chlormadinone Acetate; Contraceptives, Oral; Female; Humans; Pregnancy
PubMed: 4188179
DOI: 10.1136/bmj.4.5684.686-b -
EMBO Molecular Medicine Jul 2021Hormonal contraception exposes women to synthetic progesterone receptor (PR) agonists, progestins, and transiently increases breast cancer risk. How progesterone and...
Hormonal contraception exposes women to synthetic progesterone receptor (PR) agonists, progestins, and transiently increases breast cancer risk. How progesterone and progestins affect the breast epithelium is poorly understood because we lack adequate models to study this. We hypothesized that individual progestins differentially affect breast epithelial cell proliferation and hence breast cancer risk. Using mouse mammary tissue ex vivo, we show that testosterone-related progestins induce the PR target and mediator of PR signaling-induced cell proliferation receptor activator of NF-κB ligand (Rankl), whereas progestins with anti-androgenic properties in reporter assays do not. We develop intraductal xenografts of human breast epithelial cells from 36 women, show they remain hormone-responsive and that progesterone and the androgenic progestins, desogestrel, gestodene, and levonorgestrel, promote proliferation but the anti-androgenic, chlormadinone, and cyproterone acetate, do not. Prolonged exposure to androgenic progestins elicits hyperproliferation with cytologic changes. Androgen receptor inhibition interferes with PR agonist- and levonorgestrel-induced RANKL expression and reduces levonorgestrel-driven cell proliferation. Thus, different progestins have distinct biological activities in the breast epithelium to be considered for more informed choices in hormonal contraception.
Topics: Androgens; Animals; Cell Proliferation; Contraceptive Agents; Mice; Progestins
PubMed: 34042278
DOI: 10.15252/emmm.202114314 -
British Journal of Cancer May 1991The main subject of this hospital-based case-control study was the possible relationship between use of combined oral contraceptives (OCs) containing chlormadinone...
The main subject of this hospital-based case-control study was the possible relationship between use of combined oral contraceptives (OCs) containing chlormadinone acetate and breast cancer. Analyses were based on data from 490 cases with newly diagnosed breast cancer and 1,223 controls and were separately performed for combined OCs with and without chlormadinone. For either of the combined OCs, risk was not elevated in ever users, did not increase with duration of use and did not change with time since initial exposure or with time since most recent use. However, the relative risk was increased in current users: RR = 1.72 (0.88, 3.36) for combined OCs with chlormadinone and RR = 1.42 (1.01, 2.00) for combined OCs without chlormadinone, which is, however, explained as a screening effect. These results show that chlormadinone as a constituent of combined OCs does not influence breast cancer risk.
Topics: Adult; Breast Neoplasms; Case-Control Studies; Chlormadinone Acetate; Contraceptives, Oral, Combined; Female; Humans; Middle Aged; Risk Factors
PubMed: 1710136
DOI: 10.1038/bjc.1991.178 -
Contraception and Reproductive Medicine 2018Oral contraceptives (OCs), aside from contraceptive efficacy, have been widely known for their non-contraceptive benefits. Different progestogens component of the OCs...
BACKGROUND
Oral contraceptives (OCs), aside from contraceptive efficacy, have been widely known for their non-contraceptive benefits. Different progestogens component of the OCs have been shown to improve the skin, hair, menstrual cycle related disorders and dysmenorrhoeic pain. Thus, we compared the efficacy of OCs containing ethinyl estradiol (EE) and chlormadinone acetate (CMA) versus OCs containing EE and drospirenone (DRSP) for the treatment of acne and dysmenorrhea.
METHODS
This study was an investigator-blinded, randomized, parallel group study conducted at the Family Planning Clinic, Department of Obstetrics and Gynaecology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand. Women aged between 18 and 45 years were randomly assigned into two treatment groups, either EE/CMA at the dosage of 30 mcg/2 mg once daily (OD) or EE/DRSP at the dosage of 30 mcg/3 mg OD. The subjects were evaluated for the OC's efficacy for the treatment of acne and dysmenorrhea at baseline visit and after 1, 3, and 6 months of treatment.
RESULTS
A total of 180 women were randomized into the study. Each group had 90 women. Baseline characteristics between both groups were comparable. At Month 6, there was a significantly greater reduction of total acne lesion in the EE/CMA group than EE/DRSP (72.2% vs 64.5%; = 0.009). As per the investigator's global assessment of acne treatment, a higher proportion of the subjects from the EE/CMA group was rated "excellent" than those from the EE/DRSP (75.3% vs 49.4%). More subjects from the EE/CMA group had graded their improvement in acne as "excellent" compared to the EE/DRSP group (66.3% vs 48.3%). A higher proportion of the subjects in the EE/CMA group reported a decrease in dysmenorrhoeic pain as "much decrease" and "decrease". The absence of dysmenorrhea pain was more frequently found in the EE/CMA group and significantly seen as early as Month 1 also in the EE/CMA group compared to EE/DRSP (47.2% vs 27.3%, respectively). The treatments were generally well-tolerated in both groups. There were no significant differences between both groups for adverse events.
CONCLUSIONS
EE/CMA is more effective for the treatment of acne and dysmenorrhea in women with mild to moderate acne vulgaris and dysmenorrhea than EE/DRSP.
TRIAL REGISTRATION
Thai Clinical Trial Registry ID: TCTR20170518001 (date of registration: May 17, 2017; retrospectively registered).
PubMed: 29662684
DOI: 10.1186/s40834-018-0058-9 -
Journal of Neuro-oncology Oct 2022To report the results of systematic meningioma screening program implemented by French authorities in patients exposed to progestin therapies (cyproterone (CPA),...
PURPOSE
To report the results of systematic meningioma screening program implemented by French authorities in patients exposed to progestin therapies (cyproterone (CPA), nomegestrol (NA), and chlormadinone (CMA) acetate).
METHODS
We conducted a prospective monocentric study on patients who, between September 2018 and April 2021, underwent standardized MRI (injection of gadolinium, then a T2 axial FLAIR and a 3D-T1 gradient-echo sequence) for meningioma screening.
RESULTS
Of the 210 included patients, 15 (7.1%) had at least one meningioma; seven (7/15, 47%) had multiple meningiomas. Meningiomas were more frequent in older patients and after exposure to CPA (13/103, 13%) compared to NA (1/22, 4%) or CMA (1/85, 1%; P = 0.005). After CPA exposure, meningiomas were associated with longer treatment duration (median = 20 vs 7 years, P = 0.001) and higher cumulative dose (median = 91 g vs. 62 g, P = 0.014). Similarly, their multiplicity was associated with higher dose of CPA (median = 244 g vs 61 g, P = 0.027). Most meningiomas were ≤ 1 cm (44/58, 76%) and were convexity meningiomas (36/58, 62%). At diagnosis, patients were non-symptomatic, and all were managed conservatively. Among 14 patients with meningioma who stopped progestin exposure, meningioma burden decreased in 11 (79%) cases with no case of progression during MR follow-up.
CONCLUSION
Systematic MR screening in progestin-exposed patients uncovers small and multiple meningiomas, which can be managed conservatively, decreasing in size after progestin discontinuation. The high rate of meningiomas after CPA exposure reinforces the need for systematic screening. For NA and CMA, further studies are needed to identify patients most likely to benefit from screening.
Topics: Humans; Aged; Meningioma; Progestins; Prospective Studies; Magnetic Resonance Imaging; Meningeal Neoplasms
PubMed: 36066786
DOI: 10.1007/s11060-022-04124-2