Hormone replacement therapy

• US 20020169150A1
• Filed: 03/15/2002
• Published: 11/14/2002
• Est. Priority Date: 03/16/2001
• Status: Abandoned Application

• Current Assignee: Wyeth (Pfizer Inc.)
• Original Assignee: Wyeth (Pfizer Inc.)
• Inventors: Pickar, James H.
• Application Number:
  US10/099,361
• Publication Number:
  US 20020169150A1
• Time in Patent Office: Days
• US Class Current: 514/171
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/565 not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol
• CPC Class Codes: A61K 31/57 substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 13/02 of urine or of the urinary tract, e.g. urine acidifiers
• CPC Class Codes: A61P 15/02 for disorders of the vagina
• CPC Class Codes: A61P 15/12 for climacteric disorders
• CPC Class Codes: A61P 17/06 Antipsoriatics
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 19/08 for bone diseases, e.g. rachitism, Paget's disease
• CPC Class Codes: A61P 19/10 for osteoporosis
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 3/06 Antihyperlipidemics
• CPC Class Codes: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 31/06 for tuberculosis
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 35/00 : Antineoplastic agents
• CPC Class Codes: A61P 37/06 : Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 39/06 : Free radical scavengers or antioxidants
• CPC Class Codes: A61P 43/00 : Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 5/24 : of the sex hormones
• CPC Class Codes: A61P 5/30 : Oestrogens
• CPC Class Codes: A61P 5/34 : Gestagens
• CPC Class Codes: A61P 7/10 : Antioedematous agents; Diuretics
• CPC Class Codes: A61P 7/12 : Antidiuretics, e.g. drugs for diabetes insipidus ADH A61P5/10
• CPC Class Codes: A61P 9/00 : Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/10 : for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis

Abstract

This invention relates to methods and pharmaceutical compositions for providing hormone replacement therapy in perimenopausal, menopausal, and postmenopausal women through the continuous administration of combinations of conjugated estrogens and medroxyprogesterone acetate.

Claims

1. A method of treating or inhibiting menopausal or postmenopausal disorders in a perimenopausal, menopausal, or postmenopausal woman in need thereof, which comprises orally providing to said woman continuously and uninterruptedly over the treatment period, a combination of a daily dosage of between about 0.25 mg and about 0.1 mg conjugated estrogens and a daily dosage of between about 2.5 mg and about 0.5 mg of medroxyprogesterone acetate.

2. The method according to claim 1, wherein the conjugated estrogens is conjugated equine estrogens, USP.

3. The method according to claim 2, wherein the daily dosage of conjugated equine estrogens is between about 0.2 mg and about 0.1 mg and the daily dosage of medroxyprogesterone acetate is between about 1.5 mg and about 0.5 mg.

4. The method according to claim 3, wherein the daily dosage of medroxyprogesterone acetate is between about 1 mg and about 0.5 mg.

5. The method according to claim 4, wherein the daily dosage of conjugated equine estrogens, USP is about 0.2 mg and the daily dosage of medroxyprogesterone acetate is about 1 mg.

6. The method according to claim 1, wherein the conjugated estrogens is synthetic conjugated estrogens, A.

7. A method of treating or inhibiting vasomotor symptoms in a perimenopausal, menopausal, or postmenopausal woman in need thereof, which comprises orally providing to said woman continuously and uninterruptedly over the treatment period, a combination of a daily dosage of between about 0.25 mg and about 0.1 mg conjugated estrogens and a daily dosage of between about 2.5 mg and about 0.5 mg of medroxyprogesterone acetate.

8. The method according to claim 7, wherein the conjugated estrogens is conjugated equine estrogens, USP.

9. The method according to claim 8, wherein the daily dosage of conjugated equine estrogens is between about 0.2 mg and about 0.1 mg and the daily dosage of medroxyprogesterone acetate is between about 1.5 mg and about 0.5 mg.

10. The method according to claim 9, wherein the daily dosage of medroxyprogesterone acetate is between about 1 mg and about 0.5 mg.

11. The method according to claim 10, wherein the daily dosage of conjugated equine estrogens, USP is about 0.2 mg and the daily dosage of medroxyprogesterone acetate is about 1 mg.

12. The method according to claim 7, wherein the vasomotor symptom is hot flushes.

13. The method according to claim 7, wherein the conjugated estrogens is synthetic conjugated estrogens, A.

15. The method according to claim 14, wherein the conjugated estrogens is conjugated equine estrogens, USP.

16. The method according to claim 15, wherein the daily dosage of conjugated equine estrogens is between about 0.2 mg and about 0.1 mg and the daily dosage of medroxyprogesterone acetate is between about 1.5 mg and about 0.5 mg.

17. The method according to claim 16, wherein the daily dosage of medroxyprogesterone acetate is between about 1 mg and about 0.5 mg.

18. The method according to claim 17, wherein the daily dosage of conjugated equine estrogens, USP is about 0.2 mg and the daily dosage of medroxyprogesterone acetate is about 1 mg.

20. The method according to claim 19, wherein the conjugated estrogens is conjugated equine estrogens, USP.

21. The method according to claim 20, wherein the daily dosage of conjugated equine estrogens is between about 0.2 mg and about 0.1 mg and the daily dosage of medroxyprogesterone acetate is between about 1.5 mg and about 0.5 mg.

22. The method according to claim 21, wherein the daily dosage of medroxyprogesterone acetate is between about 1 mg and about 0.5 mg.

23. The method according to claim 22, wherein the daily dosage of conjugated equine estrogens, USP is about 0.2 mg and the daily dosage of medroxyprogesterone acetate is about 1 mg.

25. The method according to claim 24, wherein the conjugated estrogens is conjugated equine estrogens, USP.

26. The method according to claim 25, wherein the daily dosage of conjugated equine estrogens is between about 0.2 mg and about 0.1 mg and the daily dosage of medroxyprogesterone acetate is between about 1.5 mg and about 0.5 mg.

27. The method according to claim 26, wherein the daily dosage of medroxyprogesterone acetate is between about 1 mg and about 0.5 mg.

28. The method according to claim 27, wherein the daily dosage of conjugated equine estrogens, USP is about 0.2 mg and the daily dosage of medroxyprogesterone acetate is about 1 mg.

30. The method according to claim 29, wherein the conjugated estrogens is conjugated equine estrogens, USP.

31. The method according to claim 30, wherein the daily dosage of conjugated equine estrogens is between about 0.2 mg and about 0.1 mg and the daily dosage of medroxyprogesterone acetate is between about 1.5 mg and about 0.5 mg.

32. The method according to claim 31, wherein the daily dosage of medroxyprogesterone acetate is between about 1 mg and about 0.5 mg.

33. The method according to claim 32, wherein the daily dosage of conjugated equine estrogens, USP is about 0.2 mg and the daily dosage of medroxyprogesterone acetate is about 1 mg.

35. The method according to claim 34, wherein the conjugated estrogens is conjugated equine estrogens, USP.

36. The method according to claim 35, wherein the daily dosage of conjugated equine estrogens is between about 0.2 mg and about 0.1 mg and the daily dosage of medroxyprogesterone acetate is between about 1.5 mg and about 0.5 mg.

37. The method according to claim 36, wherein the daily dosage of medroxyprogesterone acetate is between about 1 mg and about 0.5 mg.

38. The method according to claim 37, wherein the daily dosage of conjugated equine estrogens, USP is about 0.2 mg and the daily dosage of medroxyprogesterone acetate is about 1 mg.

40. The composition according to claim 39, wherein the conjugated estrogens is conjugated equine estrogens, USP.

41. The composition according to claim 40, wherein the dosage of conjugated equine estrogens is between about 0.2 mg and about 0.1 mg and the dosage of medroxyprogesterone acetate is between about 1.5 mg and about 0.5 mg.

42. The composition according to claim 41, wherein the dosage of medroxyprogesterone acetate is between about 1 mg and about 0.5 mg.

43. The composition according to claim 42, wherein the dosage of conjugated equine estrogens, USP is about 0.2 mg and the dosage of medroxyprogesterone acetate is about 1 mg.

14. A method of inhibiting or retarding bone demineralization or treating or inhibiting osteoporosis in a perimenopausal, menopausal, or postmenopausal woman in need thereof, which comprises orally providing to said woman continuously and uninterruptedly over the treatment period, a combination of a daily dosage of between about 0.25 mg and about 0.1 mg conjugated estrogens and a daily dosage of between about 2.5 mg and about 0.5 mg of medroxyprogesterone acetate.

19. A method of treating or inhibiting vaginal or vulvar atrophy;

atrophic vaginitis;

vaginal dryness;

pruritus;

dyspareunia;

dysuria;

frequent urination;

urinary incontinence;

urinary tract infections in a perimenopausal, menopausal, or postmenopausal woman in need thereof, which comprises orally providing to said woman continuously and uninterruptedly over the treatment period, a combination of a daily dosage of between about 0.25 mg and about 0.1 mg conjugated estrogens and a daily dosage of between about 2.5 mg and about 0.5 mg of medroxyprogesterone acetate.

24. A method of lowering cholesterol, Lp(a), or LDL levels;

inhibiting or treating hypercholesteremia;

hyperlipidemia;

cardiovascular disease;

atherosclerosis;

peripheral vascular disease;

restenosis, vasospasm;

or inhibiting vascular wall damage from cellular events leading toward immune mediated vascular damage, in a perimenopausal, menopausal, or postmenopausal woman in need thereof, which comprises orally providing to said woman continuously and uninterruptedly over the treatment period, a combination of a daily dosage of between about 0.25 mg and about 0.1 mg conjugated estrogens and a daily dosage of between about 2.5 mg and about 0.5 mg of medroxyprogesterone acetate.

29. A method of treating or inhibiting free radical involvement in the development of cancers, central nervous system disorders, Alzheimer'"'"'s disease, bone disease, aging, inflammatory disorders, peripheral vascular disease, rheumatoid arthritis, autoimmune diseases, respiratory distress, emphysema, prevention of reperfusion injury, viral hepatitis, chronic active hepatitis, tuberculosis, psoriasis, systemic lupus erythematosus, amyotrophic lateral sclerosis, aging effects, adult respiratory distress syndrome, central nervous system trauma and stroke, or injury during reperfusion procedures in a perimenopausal, menopausal, or postmenopausal woman in need thereof, which comprises orally providing to said woman continuously and uninterruptedly over the treatment period, a combination of a daily dosage of between about 0.25 mg and about 0.1 mg conjugated estrogens and a daily dosage of between about 2.5 mg and about 0.5 mg of medroxyprogesterone acetate.

34. A method of treating or inhibiting dementias, neurodegenerative disorders, and Alzheimer'"'"'s disease;

providing neuroprotection or cognition enhancement in a perimenopausal, menopausal, or postmenopausal woman in need thereof, which comprises orally providing to said woman continuously and uninterruptedly over the treatment period, a combination of a daily dosage of between about 0.25 mg and about 0.1 mg conjugated estrogens and a daily dosage of between about 2.5 mg and about 0.5 mg of medroxyprogesterone acetate.

39. A pharmaceutical composition for use in treating menopausal or postmenopausal disorders, which comprises dosage of between about 0.25 mg and about 0.1 mg conjugated estrogens and a dosage of between about 2.5 mg and about 0.5 mg of medroxyprogesterone acetate, and a pharmaceutical carrier.

44. A pharmaceutical dosage unit which comprises which comprises conjugated estrogens, a dosage of between about 0.25 mg and about 0.1 mg conjugated estrogens and a dosage of between about 2.5 mg and about 0.5 mg of medroxyprogesterone acetate, and a pharmaceutical carrier.

45. The dosage unit according to claim 44, wherein the conjugated estrogens is conjugated equine estrogens, USP.

46. The dosage unit according to claim 45, wherein the medroxyprogesterone acetate is micronized.

47. The dosage unit according to claim 46, wherein the dosage of conjugated equine estrogens is between about 0.2 mg and about 0.1 mg and the dosage of medroxyprogesterone acetate is between about 1.5 mg and about 0.5 mg.

48. The dosage unit according to claim 47, wherein the dosage of medroxyprogesterone acetate is between about 1 mg and about 0.5 mg.

49. The dosage unit according to claim 48, wherein the dosage of conjugated equine estrogens, USP is about 0.2 mg and the dosage of medroxyprogesterone acetate is about 1 mg.

50. A method of minimizing or reducing levels of breast pain in a woman receiving hormone replacement therapy, which comprises orally providing to said woman continuously and uninterruptedly over the treatment period, a combination of a daily dosage of between about 0.25 mg and about 0.1 mg conjugated estrogens and a daily dosage of between about 2.5 mg and about 0.5 mg of medroxyprogesterone acetate.

51. The method according to claim 50, wherein the conjugated estrogens is conjugated equine estrogens, USP.

52. The method according to claim 51, wherein the daily dosage of conjugated equine estrogens is between about 0.2 mg and about 0.1 mg and the daily dosage of medroxyprogesterone acetate is between about 1.5 mg and about 0.5 mg.

53. The method according to claim 52, wherein the daily dosage of medroxyprogesterone acetate is between about 1 mg and about 0.5 mg.

54. The method according to claim 53, wherein the daily dosage of conjugated equine estrogens, USP is about 0.2 mg and the daily dosage of medroxyprogesterone acetate is about 1 mg.

55. A method of minimizing spotting or breakthrough bleeding;

or achieving amenorrhea in a woman receiving hormone replacement therapy, which comprises orally providing to said woman continuously and uninterruptedly over the treatment period, a combination of a daily dosage of between about 0.25 mg and about 0.1 mg conjugated estrogens and a daily dosage of between about 2.5 mg and about 0.5 mg of medroxyprogesterone acetate.

56. The method according to claim 55, wherein the conjugated estrogens is conjugated equine estrogens, USP.

57. The method according to claim 56, wherein the daily dosage of conjugated equine estrogens is between about 0.2 mg and about 0.1 mg and the daily dosage of medroxyprogesterone acetate is between about 1.5 mg and about 0.5 mg.

58. The method according to claim 57, wherein the daily dosage of medroxyprogesterone acetate is between about 1 mg and about 0.5 mg.

59. The method according to claim 58, wherein the daily dosage of conjugated equine estrogens, USP is about 0.2 mg and the daily dosage of medroxyprogesterone acetate is about 1 mg.

60. A method of increasing bone mineral density in a perimenopausal, menopausal, or postmenopausal woman in need thereof, which comprises orally providing to said woman continuously and uninterruptedly over the treatment period, a combination of a daily dosage of between about 0.25 mg and about 0.1 mg conjugated estrogens and a daily dosage of between about 2.5 mg and about 0.5 mg of medroxyprogesterone acetate.

61. The method according to claim 60, wherein the conjugated estrogens is conjugated equine estrogens, USP.

62. The method according to claim 61, wherein the daily dosage of conjugated equine estrogens is between about 0.2 mg and about 0.1 mg and the daily dosage of medroxyprogesterone acetate is between about 1.5 mg and about 0.5 mg.

63. The method according to claim 62, wherein the daily dosage of medroxyprogesterone acetate is between about 1 mg and about 0.5 mg.

64. The method according to claim 63, wherein the daily dosage of conjugated equine estrogens, USP is about 0.2 mg and the daily dosage of medroxyprogesterone acetate is about 1 mg.