Results of a Post-Marketing Surveillance Study
Results of a Post-Marketing Surveillance Study
Objective. This post-marketing surveillance study aimed to investigate the contraceptive efficacy and tolerability of a combination tablet containing chlormadinone acetate 2mg and ethinylestradiol 0.03mg (Belara®) in daily gynaecological practice. A secondary aim was investigation of the changes in clinical signs of androgenisation.
Design. 21 820 female patients were surveyed during a six-cycle period by 3600 gynaecologists throughout Germany.
Results. Out of 21 820 patients, a total of 19 650 women (90.1%) completed the study. Chlormadinone acetate 2mg/ethinylestradiol 0.03mg had excellent contraceptive efficacy with an adjusted Pearl index of 0.076 (unadjusted Pearl index: 0.344), calculated from 125 634 cycles of exposure. Cycle control was good,with beneficial reductions in intracyclic bleeding (22.9% in cycle 1, 1.6% in cycle 6), amenorrhoea, severe withdrawal bleeding and dysmenorrhoea. At cycle six, only 1.2, 0.4 and 0.5% of all patients complained about spotting, breakthrough bleeding and amenorrhoea, respectively. At baseline, 69.9% of the women showed androgen-related skin disorders. After six cycles of chlormadinone acetate 2mg/ ethinylestradiol 0.03mg, these disorders were improved in 86.5% of patients, including 28.5% who had complete resolution. Correspondingly, greasy or very greasy hair condition decreased from 47.0 to 13.6%. Chlormadinone acetate 2mg/ethinylestradiol 0.03mg was well tolerated; a total of two venous thromboembolic events (VTEs) occurred, and both patients recovered with appropriate treatment. Breast pain (3.6%) and migraine/headache (2.6%) were the most frequently reported adverse events. Conversely, these symptoms disappeared in most women (84.5 and 79.9%) who experienced them prior to chlormadinone acetate 2mg/ethinylestradiol 0.03mg treatment.
Conclusions. These results support the reliable contraceptive efficacy, cycle stability and tolerability reported in previous clinical trials and confirm the marked antiandrogenic properties of chlormadinone acetate 2mg/ethinylestradiol 0.03mg.
Over the last 40 years, the tolerability of combined oral contraceptives (OCs) has improved via lower dosages of the estrogen and progestogen components. Adverse events related to metabolic and coagulation parameters were reduced without compromising the contraceptive efficacy or cycle stability. A wide range of oral contraceptives is now available with different therapeutic profiles to meet individual needs. Currently, about 80 million women worldwide rely on hormonal contraceptives, all of them expecting optimal contraceptive efficacy, a reliable tolerability profile and additional benefits to their general well-being.
Cycle instability and related symptoms such as hypermenorrhoea, oligomenorrhoea, menorrhagia and dysmenorrhoea are common complaints in daily gynaecological practice. Additionally, many women experience clinical signs of androgenisation such as seborrhoea, acne, hirsutism and alopecia. For a woman, hyperandrogenism may have a pronounced negative impact on general well-being, and may often cause significant emotional and psychological problems.
Modern oral contraceptives differ from older ones primarily with regard to the progestogen component. More recently, progestogens with weak or no androgenic effects, or even with antiandrogenic properties, have been developed. Since hormonal imbalance is a key factor in the aetiology of androgen-related skin and hair changes, oral contraceptives with anti-androgenic properties have proved to be a useful approach to minimise these effects.
A monophasic combined low-dose OC containing chlormadinone acetate 2.0mg and ethinylestradiol (EE) 0.03mg per tablet (Belara®) has been developed. In contrast to other progestogens derived from the 19-nor-testosterone series, chlormadinone acetate is a derivative of the naturally secreted hormone progesterone and has marked anti-androgenic properties. In addition to its anti-androgenic profile, chlormadinone acetate is not expected to interfere with estrogenrelated protective effects on the cardiovascular system.
In addition, chlormadinone acetate differs from other progestogens with regard to its hepatic safety profile; it does not significantly inhibit the enzyme activity of CYP1A2, CYP2C9, CYP2D6 and CYP3A4, and it does not interfere with the hepatic 5-alpha-reductase.
In a multicentre, phase III trial over 24 cycles in 1655 women, chlormadinone acetate 2mg/ ethinylestradiol 0.03mg was well tolerated and demonstrated excellent contraceptive efficacy (adjusted Pearl index of 0.27), high-level cycle stability and beneficial anti-androgenic effects on both hair and skin.
Chlormadinone acetate 2mg/ethinylestradiol 0.03mg has been marketed in Germany since 1999, and there is nowa great deal of experiencewith this oral combination contraceptive. Post-marketing surveillance studies are a legal requirement in Germany for newly marketed drugs, in order to confirm the results of premarketing clinical trials. The aim of this six-cycle post-marketing study was to survey the contraceptive efficacy and tolerability of chlormadinone acetate 2mg/ethinylestradiol 0.03mg in a large sample population during routine clinical use. In addition, the influence of this combination OC on clinical signs of androgenisation were evaluated.
Objective. This post-marketing surveillance study aimed to investigate the contraceptive efficacy and tolerability of a combination tablet containing chlormadinone acetate 2mg and ethinylestradiol 0.03mg (Belara®) in daily gynaecological practice. A secondary aim was investigation of the changes in clinical signs of androgenisation.
Design. 21 820 female patients were surveyed during a six-cycle period by 3600 gynaecologists throughout Germany.
Results. Out of 21 820 patients, a total of 19 650 women (90.1%) completed the study. Chlormadinone acetate 2mg/ethinylestradiol 0.03mg had excellent contraceptive efficacy with an adjusted Pearl index of 0.076 (unadjusted Pearl index: 0.344), calculated from 125 634 cycles of exposure. Cycle control was good,with beneficial reductions in intracyclic bleeding (22.9% in cycle 1, 1.6% in cycle 6), amenorrhoea, severe withdrawal bleeding and dysmenorrhoea. At cycle six, only 1.2, 0.4 and 0.5% of all patients complained about spotting, breakthrough bleeding and amenorrhoea, respectively. At baseline, 69.9% of the women showed androgen-related skin disorders. After six cycles of chlormadinone acetate 2mg/ ethinylestradiol 0.03mg, these disorders were improved in 86.5% of patients, including 28.5% who had complete resolution. Correspondingly, greasy or very greasy hair condition decreased from 47.0 to 13.6%. Chlormadinone acetate 2mg/ethinylestradiol 0.03mg was well tolerated; a total of two venous thromboembolic events (VTEs) occurred, and both patients recovered with appropriate treatment. Breast pain (3.6%) and migraine/headache (2.6%) were the most frequently reported adverse events. Conversely, these symptoms disappeared in most women (84.5 and 79.9%) who experienced them prior to chlormadinone acetate 2mg/ethinylestradiol 0.03mg treatment.
Conclusions. These results support the reliable contraceptive efficacy, cycle stability and tolerability reported in previous clinical trials and confirm the marked antiandrogenic properties of chlormadinone acetate 2mg/ethinylestradiol 0.03mg.
Over the last 40 years, the tolerability of combined oral contraceptives (OCs) has improved via lower dosages of the estrogen and progestogen components. Adverse events related to metabolic and coagulation parameters were reduced without compromising the contraceptive efficacy or cycle stability. A wide range of oral contraceptives is now available with different therapeutic profiles to meet individual needs. Currently, about 80 million women worldwide rely on hormonal contraceptives, all of them expecting optimal contraceptive efficacy, a reliable tolerability profile and additional benefits to their general well-being.
Cycle instability and related symptoms such as hypermenorrhoea, oligomenorrhoea, menorrhagia and dysmenorrhoea are common complaints in daily gynaecological practice. Additionally, many women experience clinical signs of androgenisation such as seborrhoea, acne, hirsutism and alopecia. For a woman, hyperandrogenism may have a pronounced negative impact on general well-being, and may often cause significant emotional and psychological problems.
Modern oral contraceptives differ from older ones primarily with regard to the progestogen component. More recently, progestogens with weak or no androgenic effects, or even with antiandrogenic properties, have been developed. Since hormonal imbalance is a key factor in the aetiology of androgen-related skin and hair changes, oral contraceptives with anti-androgenic properties have proved to be a useful approach to minimise these effects.
A monophasic combined low-dose OC containing chlormadinone acetate 2.0mg and ethinylestradiol (EE) 0.03mg per tablet (Belara®) has been developed. In contrast to other progestogens derived from the 19-nor-testosterone series, chlormadinone acetate is a derivative of the naturally secreted hormone progesterone and has marked anti-androgenic properties. In addition to its anti-androgenic profile, chlormadinone acetate is not expected to interfere with estrogenrelated protective effects on the cardiovascular system.
In addition, chlormadinone acetate differs from other progestogens with regard to its hepatic safety profile; it does not significantly inhibit the enzyme activity of CYP1A2, CYP2C9, CYP2D6 and CYP3A4, and it does not interfere with the hepatic 5-alpha-reductase.
In a multicentre, phase III trial over 24 cycles in 1655 women, chlormadinone acetate 2mg/ ethinylestradiol 0.03mg was well tolerated and demonstrated excellent contraceptive efficacy (adjusted Pearl index of 0.27), high-level cycle stability and beneficial anti-androgenic effects on both hair and skin.
Chlormadinone acetate 2mg/ethinylestradiol 0.03mg has been marketed in Germany since 1999, and there is nowa great deal of experiencewith this oral combination contraceptive. Post-marketing surveillance studies are a legal requirement in Germany for newly marketed drugs, in order to confirm the results of premarketing clinical trials. The aim of this six-cycle post-marketing study was to survey the contraceptive efficacy and tolerability of chlormadinone acetate 2mg/ethinylestradiol 0.03mg in a large sample population during routine clinical use. In addition, the influence of this combination OC on clinical signs of androgenisation were evaluated.