Use of combined oral contraceptives containing nomegestrol acetate and estradiol

Abstract

The present invention relates to the use of compositions comprising nomegestrol acetate (NOMAC) and estradiol or an ester thereof. The compositions are for use in reducing the risk of venous thromboembolism (VTE) associated with the use of combined oral contraceptives (COC). The compositions may be used in methods of contraception and/or methods of treatment in women having conditions linked to menstruation and/or fertility.

1 . A composition for use in reducing the risk of venous thromboembolism associated with the use of combined oral contraceptives, wherein the composition comprises nomegestrol acetate and estradiol or an ester thereof. 
     
     
         2 . The composition for use according to  claim 1 , wherein the risk of deep vein thrombosis is reduced. 
     
     
         3 . The composition for use according to  claim 1  or  claim 2 , wherein the risk of pulmonary embolism is reduced. 
     
     
         4 . The composition for use according to any one of the preceding claims, wherein the risk of venous thromboembolism is reduced relative to a combined oral contraceptive containing levonorgestrel; and optionally ethinylestradiol. 
     
     
         5 . The composition for use according to any one of the preceding claims, wherein the risk of venous thromboembolism is reduced by at least 40%. 
     
     
         6 . The composition for use according to any one of the preceding claims, wherein the Hazard Ratio is 0.5-0.6. 
     
     
         7 . The composition for use according to any one of the preceding claims, wherein the composition is administered to a woman or women of child-bearing age as a means of contraception. 
     
     
         8 . The composition for use according to any one of the preceding claims, wherein the composition is administered to a woman or women for a non-contraceptive use. 
     
     
         9 . The composition for use according to  claim 8  wherein the non-contraceptive use is selected from (i) the treatment of a condition selected from painful menstrual bleeding, heavy and/or prolonged menstrual bleeding, acne, ovarian cysts, polycystic ovary syndrome, premenstrual syndrome, endometriosis, or premenstrual dysphoric disorder; and/or (ii) menstrual cycle regulation. 
     
     
         10 . The composition for use according to any one of the preceding claims, wherein the composition is administered to a woman or women identified as at increased risk of venous thromboembolism. 
     
     
         11 . The composition for use according to any one of the preceding claims, wherein the composition is administered to a woman or women 35 years of age or above. 
     
     
         12 . The composition for use according to any one of the preceding claims, wherein the composition is administered to a woman or women having a body mass index in excess of 30 kg/m 2  and/or a woman or women with diabetes. 
     
     
         13 . The composition for use according to any one of the preceding claims, wherein the composition is administered to a woman or women having a condition selected from: cancer; systemic lupus erythematosus; haemolytic uraemic syndrome; chronic inflammatory bowel disease, optionally Crohn's disease or ulcerative colitis; and sickle cell disease. 
     
     
         14 . The composition for use according to any one of the preceding claims, wherein the composition is administered to a woman or women who has/have not received prior combined oral contraceptive treatment. 
     
     
         15 . The composition for use according to any one of  claims 1 - 13 , wherein the composition is administered to a woman or women who have previously received combined oral contraceptive treatment. 
     
     
         16 . The composition for use according to any one of the preceding claims, wherein the nomegestrol acetate and estradiol or ester thereof are present in the composition in a weight ratio of approximately 1.67 to 1. 
     
     
         17 . The composition for use according to any one of the preceding claims, wherein the nomegestrol acetate is present in an amount ranging from about 1.5 mg to about 3.75 mg. 
     
     
         18 . The composition for use according to any one of the preceding claims, wherein the estradiol or ester thereof is present in an amount ranging from about 0.5 mg to about 3 mg. 
     
     
         19 . The composition for use according to any one of the preceding claims, wherein the estradiol is 17β-estradiol; optionally wherein the 17β-estradiol is in hemihydrate form. 
     
     
         20 . The composition for use according to any one of the preceding claims, wherein the nomegestrol acetate is present in an amount of about 2.5 mg and the estradiol is present in an amount of about 1.5 mg. 
     
     
         21 . The composition for use according to any one of the preceding claims, wherein the composition is administered daily for a period of 21 to 28 days; optionally for a period of 24 consecutive days. 
     
     
         22 . The composition for use according to any one of the preceding claims, wherein the composition is in the form of plain or film-coated tablets, sugar-coated tablets, soft gelatin capsules, wafer capsules, pills, cachets or powders. 
     
     
         23 . The composition for use according to any one of the preceding claims, wherein the composition further comprises at least one excipient selected from: lactose monohydrate; microcrystalline cellulose (E460); crospovidone (E1201); talc (E553b); magnesium stearate (E572); and colloidal anhydrous silica; or any combination thereof. 
     
     
         24 . The composition for use according to any one of the preceding claims wherein the composition comprises: 2.5 mg nomegestrol acetate; 1.5 mg 17β-estradiol; 57.7 mg lactose monohydrate; 14 mg microcrystalline cellulose; 2.4 mg crospovidone; 0.7 mg talc; 0.7 mg magnesium stearate, and 0.44 mg colloidal anhydrous silica. 
     
     
         25 . The composition for use according to any one of the preceding claims, wherein the composition is provided as a pharmaceutical kit comprising a plurality of dosage units and optionally at least one placebo. 
     
     
         26 . Use of a composition comprising nomegestrol acetate and estradiol or an ester thereof as a contraceptive; wherein the risk of venous thromboembolism associated with the use of combined oral contraceptives is reduced. 
     
     
         27 . A method of contraception, wherein the method comprises administering to a woman a composition comprising nomegestrol acetate and estradiol or an ester thereof, wherein the risk of venous thromboembolism associated with the use of combined oral contraceptives is reduced in the woman administered the composition. 
     
     
         28 . A composition for use in a method of treating a condition selected from: painful menstrual bleeding; heavy and/or prolonged menstrual bleeding; acne; ovarian cysts; polycystic ovary syndrome; premenstrual syndrome; endometriosis; and premenstrual dysphoric disorder, wherein the composition comprises nomegestrol acetate and estradiol or an ester thereof; and wherein the risk of venous thromboembolism associated with the use of combined oral contraceptives is reduced. 
     
     
         29 . A method of reducing the risk of venous thromboembolism associated with the use of combined oral contraceptives, wherein the method comprises administering to a woman a composition comprising nomegestrol acetate and estradiol or an ester thereof.