Claims for Patent: 4,826,831

Summary for Patent: 4,826,831

Title:	Method of hormonal treatment for menopausal or post-menopausal disorders involving continuous administration of progestogens and estrogens
Abstract:	A method of hormonally treating menopausal (including perimenopausal and post-menopausal) disorders in women, a composition, and a multi-preparation pack therefor. The administrative regimen to which the pack is particularly adapted comprises continuously and uninterruptedly administering a progestogen to a woman while cyclically administering an estrogen by using a repetitive dosage regimen. This regimen calls for administering the estrogen continuously for a period of time between about 20 and about 120 days, followed by terminating administering the estrogen for a period of time between about 3 and about 7 days. Alternatively, both the progestogen and estrogen may be administered for the full treatment period without interruption. The regimen avoids many of the problems associated with the administration of estrogen alone or with progestogen administered according to conventional regimens, and also avoids problems associated with such conventional regimens by maintaining the estrogen and progestogen at low daily dosage levels of between 0.005 mg and 2.5 mg estrogen and 0.25 mg and 30 mg progestogen.
Inventor(s):	Plunkett; Earl R. (London, CA), Wolfe; Bernard M. J. (London, CA)
Assignee:	Pre Jay Holdings Limited (CA) WOCO Investments Ltd. (CA)
Application Number:	06/635,236
Patent Claims:	1. A method of hormonally treating menopausal or post-menopausal disorders in a woman, comprising administering to said woman continuously and uninterrupted1y both progestogen and estrogen in daily dosage units of progestogen equivalent to laevo-norgestrel dosages of from about 0.025 mg to about 0.075 mg, and of estrogen equivalent to estradiol dosages of about 0.5 mg to about 2.0 mg. 2. The method of claim 1 wherein said estrogen is 17 .beta.-estradiol and said progestogen is d1-norgestrel or laevo-norgestrel, the daily dosage level of said 17 .beta. -estradiol being about 1 mg, the daily dosage level of said d1-norgestrel (where present) being about 100 micrograms, and the daily dosage of said laevo-norgestrel (where present being about 50 micrograms. 3. A method of hormonally treating perimenopausal, menopausal or post-menopausal disorders in a woman, comprising: A. continuously and uninterrupted1y administering a progestogen to said woman in daily dosage units of progestogen equivalent to laevo-norgestrel dosages of from about 0.025 mg to about 0.075 mg, and B. cyclically administering an estrogen to said woman by repetitively using a dosage regimen comprising: (i) administering said estrogen continuously for a period of time between about 20 and about 120 days in daily dosage units of estrogen equivalent to estradiol dosages of from about 0.500 mg to about 2 mg, followed by (ii) terminating administering said estrogen for a period of time between about 3 and about 7 days. 4. The method of claim 3 wherein said progestogen is selected from the following group, with respective maximum and minimum daily dosage levels as follows: 5. The method of claim 3 wherein said estrogen is selected from the following group, with respective maximum and minimum daily dosage levels as follows: 6. The method of claim 5 or claim 4 wherein said estrogen is selected from the following group, with respective daily dosage levels as follows: 7. The method of claim 5 wherein said progestogen is selected from the following group, with respective daily dosage levels as follows: 8. The method of any of claims 5 wherein said estrogen and said progestogen are selected from the following combinations: Estradiol/Laevo-norgestrel Estradiol 17.beta./Laevo-norgestrel Conjugated equine estrogens/Laevo-norgestrel Estradiol/d1-norgestrel Estradiol 17.beta./d1-norgestrel Estradiol valerate/Laevonorgestrel Estradiol valerate/d1-norgestrel Conjugated equine estrogens/d1-norgestrel Estradiol/Norethindrone (norethisterone) Estradiol 17.beta./Norethindrone (norethisterone) Estradiol valerate/Norethindrone (norethiserone) Conjugated equine estrogens/Norethindrone (norethisterone) Estradiol/Norethindrone (norethisterone) acetate Estradiol 17.beta./Norethindrone (norethisterone) acetate Estradiol valerate/Norethindrone (norethisterone) acetate Conjugated equine estrogen/Norethindrone (norethisterone) acetate Estradiol/Medroxyprogesterone acetate Estradiol 17.beta./Medroxyprogesterone acetate Estradiol valerate/Medroxyprogesterone acetate Conjugated equine estrogen/Medroxyprogesterone acetate. 9. The method of claim 8 wherein said estrogen is 17.beta.-estradiol and said progestogen is d1-norgestrel or laevo-norgestrel. 10. The method of claim 9 wherein the daily dosage level of said 17.beta.-estradiol is between about 0.5 mg and about 2 mg, the daily dosage level of said d1-norgestrel, where present, is between about 50 and about 150 micrograms and the daily dosage level of said laevo-norgestrel, where present, is between about 25 and about 75 micrograms. 11. The method of claim 10 wherein the daily dosage level of said d1-norgestrel is about 75 micrograms. 12. The method of claim 1 or 3 wherein said estrogen is a synthetic estrogen. 13. The method of claim 12 wherein said synthetic estrogen is selected from the group consisting of ethinyl estradiol, mestranol and quinestranol. 14. The method of claim 1 or 3 wherein said estrogen is a natural estrogen. 15. The method of claim 14 wherein said natural estrogen is selected from the group consisting of conjugated equine estrogens, estradiol, estradiol-17.beta. estradiol valerate, estrone, piperazine estrone sulphate, estriol, estriol succinate and polyestrol phosphate. 16. The method of claim 1 or 3, wherein said progestogen is selected from the group consisting of laevo-norgestrel, d1-norge, trel, norethindrone (norethisterone), norethindrone (norethisterone) acetate, ethynodiol diacetate, dydrogesterone, medroxyprogesterone acetate, norethynodrel, allylestrenol, lynoestrenol, quingestanol acetate, medrogestone, norgestrienone, dimethisterone, ethisterone, and cyprotecone acetate. 17. A pharmaceutical composition for the hormonal treatment of perimenopausal, menopausal and post-menopausal disorders in a woman, said composition being in implantable or intramuscularly injectable form and comprising, in association with a pharmaceutically acceptable barrier, sufficient progestogen and estrogen to provide dosage levels to said woman equivalent to orally administered daily dosages of progestogen equivalent to laevo-norgestrel dosages of from about 0.025 mg to about 0.075 mg and of estrogen equivalent to estradiol dosages of about 0.5 mg to about 2 mg. 18. The pharmaceutical composition of claim 17 in implantable form, wherein said estrogen is selected from the group consisting of estradiol, estradiol-17.beta., and estradiol valerate. 19. The pharmaceutical composition of claim 18 or 17 in implantable form, wherein said progestogen is selected from the group consisting of laevo-norgestrel, d1-norgestrel, norgestrienone, and norethindrone acetate. 20. The pharmaceutical composition of claim 17 in injectable form, wherein said progestogen is selected from the group consisting of medroxyprogesterone acetate, norethindrone enanthate, gestronol hexanoate, and algestone acetophenide.