Hormone replacement therapy

• US 20010034340A1
• Filed: 03/15/2001
• Published: 10/25/2001
• Est. Priority Date: 03/20/2000
• Status: Abandoned Application

• Current Assignee: Wyeth (Pfizer Inc.)
• Original Assignee: American Home Products Corporation (Pfizer Inc.)
• Inventors: Pickar, James H.
• Application Number:
  US09/808,878
• Publication Number:
  US 20010034340A1
• Time in Patent Office: Days
• US Class Current: 514/177
• 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: 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 15/00 Drugs for genital or sexual disorders for disorders of sex hormones A61P5/24; Contraceptives
• 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 19/00 Drugs for skeletal disorders
• 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 21/04 for myasthenia gravis
• 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 3/00 Drugs for disorders of the metabolism of the blood or the extracellular fluid A61P7/00
• CPC Class Codes: A61P 3/06 Antihyperlipidemics
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61P 31/20 : for DNA viruses
• CPC Class Codes: A61P 35/00 : Antineoplastic agents
• CPC Class Codes: A61P 37/02 : Immunomodulators
• CPC Class Codes: A61P 5/00 : Drugs for disorders of the endocrine system
• CPC Class Codes: A61P 5/12 : for decreasing, blocking or antagonising the activity of the posterior pituitary hormones
• CPC Class Codes: A61P 5/24 : of the sex hormones
• CPC Class Codes: A61P 5/30 : Oestrogens
• 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 conjugated estrogens and a daily dosage of about 1.5 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 0.625 mg and about 0.3 mg.

4. The method according to

claim 3

, wherein the daily dosage of conjugated equine estrogens, USP is between about 0.45 mg and about 0.3 mg.

5. The method according to

claim 4

, wherein the daily dosage of conjugated equine estrogens, USP is about 0.3 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 conjugated estrogens and a daily dosage of about 1.5 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 0.625 mg and about 0.3 mg.

10. The method according to

claim 9

, wherein the daily dosage of conjugated equine estrogens, USP is between about 0.45 mg and about 0.3 mg.

11. The method according to

claim 10

, wherein the daily dosage of conjugated equine estrogens, USP is about 0.3 mg.

12. The method according to

claim 8

, wherein the vasomotor symptom is hot flushes.

13. The method according to

claim 7

, wherein the conjugated estrogens is synthetic conjugated estrogens, A.

14. The method according to

claim 13

, wherein the vasomotor symptom is hot flushes.

15. 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 conjugated estrogens and a daily dosage of about 1.5 mg of medroxyprogesterone acetate.

16. The method according to

claim 15

, wherein the conjugated estrogens is conjugated equine estrogens, USP.

17. The method according to

claim 16

, wherein the daily dosage of conjugated equine estrogens is between about 0.625 mg and about 0.3 mg.

18. The method according to

claim 17

, wherein the daily dosage of conjugated equine estrogens, USP is between about 0.45 mg and about 0.3 mg.

19. The method according to

claim 18

, wherein the daily dosage of conjugated equine estrogens, USP is about 0.3 mg.

20. 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 conjugated estrogens and a daily dosage of about 1.5 mg of medroxyprogesterone acetate.

21. The method according to

claim 20

, wherein the conjugated estrogens is conjugated equine estrogens, USP.

22. The method according to

claim 21

, wherein the daily dosage of conjugated equine estrogens is between about 0.625 mg and about 0.3 mg.

23. The method according to

claim 22

, wherein the daily dosage of conjugated equine estrogens, USP is between about 0.45 mg and about 0.3 mg.

24. The method according to

claim 23

, wherein the daily dosage of conjugated equine estrogens, USP is about 0.3 mg.

25. A method of lowering cholesterol, triglycerides, 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 conjugated estrogens and a daily dosage of about 1.5 mg of medroxyprogesterone acetate.

30. 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 conjugated estrogens and a daily dosage of about 1.5 mg of medroxyprogesterone acetate.

26. The method according to

claim 27

, wherein the conjugated estrogens is conjugated equine estrogens, USP.

27. The method according to

claim 28

, wherein the daily dosage of conjugated equine estrogens is between about 0.625 mg and about 0.3 mg.

28. The method according to

claim 29

, wherein the daily dosage of conjugated equine estrogens, USP is between about 0.45 mg and about 0.3 mg.

29. The method according to

claim 30

, wherein the daily dosage of conjugated equine estrogens, USP is about 0.3 mg.

35. 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 conjugated estrogens and a daily dosage of about 1.5 mg of medroxyprogesterone acetate.

31. The method according to

claim 32

, wherein the conjugated estrogens is conjugated equine estrogens, USP.

32. The method according to

claim 33

, wherein the daily dosage of conjugated equine estrogens is between about 0.625 mg and about 0.3 mg.

33. The method according to

claim 34

, wherein the daily dosage of conjugated equine estrogens, USP is between about 0.45 mg and about 0.3 mg.

34. The method according to

claim 35

, wherein the daily dosage of conjugated equine estrogens, USP is about 0.3 mg.

40. A pharmaceutical composition for use in treating menopausal or postmenopausal disorders, which comprises conjugated estrogens, a dosage of about 1.5 mg medroxyprogesterone acetate, and a pharmaceutical carrier.

36. The method according to

claim 37

, wherein the conjugated estrogens is conjugated equine estrogens, USP.

37. The method according to

claim 38

, wherein the daily dosage of conjugated equine estrogens is between about 0.625 mg and about 0.3 mg.

38. The method according to

claim 39

, wherein the daily dosage of conjugated equine estrogens, USP is between about 0.45 mg and about 0.3 mg.

39. The method according to

claim 40

, wherein the daily dosage of conjugated equine estrogens, USP is about 0.3 mg.

43. The composition according to

claim 43

, wherein the dosage of conjugated equine estrogens, USP is about 0.30 mg.

41. The composition according to

claim 42

, wherein the conjugated estrogens is conjugated equine estrogens, USP.

42. The composition according to

claim 43

, wherein the dosage of conjugated equine estrogens, USP is about 0.45 mg.

61. The method according to

claim 62

, wherein the conjugated estrogens is conjugated equine estrogens, USP.

62. The method according to

claim 63

, wherein the daily dosage of conjugated equine estrogens is between about 0.625 mg and about 0.3 mg.

63. The method according to

claim 64

, wherein the daily dosage of conjugated equine estrogens, USP is between about 0.45 mg and about 0.3 mg.

64. The method according to

claim 65

, wherein the daily dosage of conjugated equine estrogens, USP is about 0.3 mg.

65. The pharmaceutical composition according to

claim 42

, wherein the conjugated estrogens is synthetic conjugated estrogens, A.

44. A pharmaceutical oral dosage unit which comprises which comprises conjugated estrogens, a dosage of about 1.5 mg of medroxyprogesterone acetate, and a pharmaceutical carrier.

47. The dosage unit according to

claim 47

, wherein the dosage of conjugated equine estrogens, USP is about 0.45 mg.

45. The dosage unit according to

claim 46

, wherein the conjugated estrogens is conjugated equine estrogens, USP.

46. The dosage unit according to

claim 47

, wherein the medroxyprogesterone acetate is micronized.

48. The dosage unit according to

claim 47

, wherein the dosage of conjugated equine estrogens, USP is about 0.30 mg.

66. The pharmaceutical dosage unit according to

claim 46

, wherein the conjugated estrogens is synthetic conjugated estrogens, A.

49. 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 conjugated estrogens and a daily dosage of about 1.5 mg of medroxyprogesterone acetate.

54. 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 conjugated estrogens and a daily dosage of about 1.5 mg of medroxyprogesterone acetate.

50. The method according to

claim 51

, wherein the conjugated estrogens is conjugated equine estrogens, USP.

51. The method according to

claim 52

, wherein the daily dosage of conjugated equine estrogens is between about 0.625 mg and about 0.3 mg.

52. The method according to

claim 53

, wherein the daily dosage of conjugated equine estrogens, USP is between about 0.45 mg and about 0.3 mg.

53. The method according to

claim 54

, wherein the daily dosage of conjugated equine estrogens, USP is about 0.3 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 conjugated estrogens and a daily dosage of about 1.5 mg of medroxyprogesterone acetate.

55. The method according to

claim 56

, wherein the time for minimizing spotting or breakthrough bleeding or achieving the onset of amenorrhea is hastened.

56. The method according to

claim 57

, wherein the conjugated estrogens is conjugated equine estrogens, USP.

57. The method according to

claim 58

, wherein the daily dosage of conjugated equine estrogens is between about 0.625 mg and about 0.3 mg.

58. The method according to

claim 59

, wherein the daily dosage of conjugated equine estrogens, USP is between about 0.45 mg and about 0.3 mg.

59. The method according to

claim 60

, wherein the daily dosage of conjugated equine estrogens, USP is about 0.3 mg.