Transdermal contraceptive hormones delivery

Abstract

Dosing regimens for transdermal delivery of hormones comprising a variable treatment cycle and a fixed rest interval are disclosed.

1 . A method of preventing pregnancy in a woman that comprises, during an eight week or a twelve week treatment cycle having a treatment interval of seven weeks or eleven weeks and a rest interval of one week:
 (A) transdermally administering a contraceptively effective amount of a progestin and an estrogen during the treatment interval by successive applications of transdermal hormone delivery devices; and   (B) transdermally administering low dose progestin and low dose estrogen throughout the rest interval by application of a transdermal hormone delivery device;   wherein   the amount of the progestin delivered during the rest interval is 25% to 75% of the amount of the progestin delivered during the treatment interval; and   the amount of the estrogen delivered during the rest interval is 25% to 75% of the amount of the estrogen delivered during the treatment interval.   
     
     
         2 . The method of  claim 1 , comprising:
 (A) transdermally administering the contraceptively effective amounts of the progestin and the estrogen during the treatment interval by successive weekly applications of seven or eleven transdermal hormone delivery devices, one for each week of each treatment interval; and   (B) transdermally administering the low dose progestin and low dose estrogen throughout the rest interval by application of a transdermal hormone delivery device during the rest interval.   
     
     
         3 . The method of  claim 1 , wherein the rest interval device comprises the same progestin and estrogen as the treatment interval devices. 
     
     
         4 . The method of  claim 2 , wherein the rest interval device has the same hormone concentrations as the treatment interval device but is a fraction of the size of the treatment interval device. 
     
     
         5 . The method of  claim 2 , wherein the rest interval device is the same size as the treatment interval device but comprises reduced hormone amounts compared to the treatment interval device. 
     
     
         6 . The method of  claim 2 , wherein: (a) the amount of progestin delivered during the rest interval is ¼, ⅓, ½, ⅔, or ¾ of the amount delivered from each treatment interval device during the treatment interval; and (b) the amount of estrogen delivered during the rest interval is ¼, ⅓, ½, ⅔, or ¾ of the amount delivered from each treatment interval device during the treatment interval. 
     
     
         7 . The method of  claim 1 , wherein the rest interval device is worn during all of the rest interval. 
     
     
         8 . The method of  claim 1 , wherein the estrogen in the treatment interval devices and the rest interval device is ethinyl estradiol. 
     
     
         9 . The method of  claim 8 , in which the dosing regimen provides an average serum concentration of about 15 to about 65 pg/ml of ethinyl estradiol during each treatment interval, in a given woman or population of women. 
     
     
         10 . The method of  claim 1 , wherein the progestin is selected from levonorgestrel, norgestrel, norgestimate, desogestrel, gestodene, norethindrone, norethynodrel, hydrogesterone, ethynodiol dicetate, hydroxyprogesterone caproate, medroxyprogesterone acetate, norethindrone acetate, progesterone, megestrol acetate, gestogen, or any combination thereof. 
     
     
         11 . A kit comprising:
 (a) seven or eleven, or a multiple of seven or eleven, transdermal hormone delivery treatment interval devices, each treatment interval device comprising a progestin and an estrogen in an amount sufficient to reduce the risk of pregnancy, each being intended for wear for one week;   (b) one rest interval device for each seven or eleven treatment interval devices, intended for wear during a one week rest interval between successive seven-week or eleven-week treatment intervals, wherein the rest interval device comprises: (1) low dose progestin in an amount sufficient to deliver 25% to 75% the amount of the progestin delivered during each week of the treatment interval, and (2) low dose estrogen in an amount sufficient to deliver 25% to 75% the amount of the estrogen delivered during each week of the treatment interval; and   (c) instructions for use of the devices in an eight-week or twelve-week treatment cycle comprising a seven-week or an eleven week treatment interval and a one-week rest interval, the method comprising (i) transdermally administering a contraceptively effective amount of a progestin and an estrogen during the treatment interval by successive applications of the seven or eleven transdermal hormone treatment interval devices, one for each week of the treatment interval, and (ii) transdermally administering low dose progestin and low dose estrogen throughout the rest interval by application of the low dose rest interval device during the rest interval.   
     
     
         12 . The kit of  claim 11 , wherein the rest interval device comprises the same progestin and estrogen as the treatment interval devices. 
     
     
         13 . The kit of  claim 11 , wherein the rest interval device has the same hormone concentrations as the treatment interval device but is a fraction of the size of the treatment interval device. 
     
     
         14 . The kit of  claim 11 , wherein the rest interval device is the same size as the treatment interval device but comprises reduced amounts of estrogen and progestin compared to the treatment interval device. 
     
     
         15 . The kit of  claim 11 , wherein the treatment interval device and the rest interval device are formulated such that: (a) the amount of progestin delivered during the rest interval is ¼, ⅓, ½, ⅔ or ¾ of the amount delivered from each treatment interval device during the treatment interval; and (b) the amount of estrogen delivered during the rest interval is ¼, ⅓, ½, ⅔ or ¾ of the amount delivered from each treatment interval device during the treatment interval. 
     
     
         16 . The kit of  claim 11 , wherein the estrogen in the treatment interval devices and the rest interval device is ethinyl estradiol. 
     
     
         17 . The kit of  claim 16 , in which the treatment device is formulated to deliver an average serum concentration of about 15 to about 65 pg/ml of ethinyl estradiol during each treatment interval, in a given woman or population of women. 
     
     
         18 . The kit of  claim 11 , wherein the progestin is selected from levonorgestrel, norgestrel, norgestimate, desogestrel, gestodene, norethindrone, norethynodrel, hydrogesterone, ethynodiol dicetate, hydroxyprogesterone caproate, medroxyprogesterone acetate, norethindrone acetate, progesterone, megestrol acetate, gestogen, or any combination thereof.