NATURAL COMBINATION HORMONE REPLACEMENT FORMULATIONS AND THERAPIES

1 .- 36 . (canceled)

37 . A pharmaceutical composition for administering estradiol and progesterone to a human female subject having a vasomotor symptom associated with estrogen deficiency, the composition comprising:

about 0.25 mg estradiol,

progesterone, and

a solubilizing agent, the solubilizing agent comprising a C6-C12 oil,

wherein the estradiol and the progesterone are present in the solubilizing agent, and at least 80% of the estradiol is solubilized; and

wherein administration of the composition to the subject produces, in a plasma sample from the subject, one or both parameters selected from:

(i) an area under the curve (AUC) (0-t) for estradiol that is from 140.3733 pg·hr/ml to 219.3333 pg·hr/ml; and

(ii) a C max for estradiol that is from 6.4790 pg/ml to 10.1235 pg/ml.

38 . The pharmaceutical composition of claim 37 , wherein administration of the composition to the subject produces both an AUC (0-t) for estradiol that is from 140.3733 pg·hr/ml to 219.3333 pg·hr/ml, and a C max for estradiol that is from 6.4790 pg/ml to 10.1235 pg/ml.

39 . The pharmaceutical composition of claim 37 , comprising about 50 mg progesterone, wherein administration of the composition to the subject further produces, in a plasma sample from the subject, one or both parameters selected from:

(i) an AUC (0-t) for progesterone that is from 24.0174 ng·hr/ml to 37.5272 ng·hr/ml; and

(ii) a C max for progesterone that is from 17.8444 ng/ml to 27.8819 ng/ml.

40 . The pharmaceutical composition of claim 37 , wherein

administration of the composition to the subject further produces, in a plasma sample from the subject, one or both parameters selected from:

(i) an AUC (0-t) for estrone that is from 909.6091 pg·hr/ml to 1421.2642 pg·hr/ml; and

(ii) a C max for estrone that is from 42.6549 pg/ml to 66.6483 pg/ml.

41 . The pharmaceutical composition of claim 37 , wherein

administration of the composition to the subject further produces, in a plasma sample from the subject, one or both parameters selected from:

(i) an AUC (0-t) for total estrone that is from 20.1752 ng·hr/ml to 31.5238 ng·hr/ml; and

(ii) a C max for total estrone that is from 3.5429 ng/ml to 5.5358 ng/ml.

42 . A method for treating a human female subject having a vasomotor symptom associated with estrogen deficiency, the method comprising administering to the subject a pharmaceutical composition of claim 37 , wherein the pharmaceutical composition is administered to the subject once daily for at least one month.

43 . A pharmaceutical composition for administering estradiol and progesterone to a human female subject having a vasomotor symptom associated with estrogen deficiency, the composition comprising:

about 0.5 mg estradiol,

progesterone, and

a solubilizing agent, the solubilizing agent comprising a C6-C12 oil,

wherein the estradiol and the progesterone are present in the solubilizing agent, and at least 80% of the estradiol is solubilized; and

wherein administration of the composition to the subject produces, in a plasma sample from the subject, one or both parameters selected from:

(i) an area under the curve (AUC) (0-t) for estradiol that is from 280.7467 pg·hr/ml to 438.6667 pg·hr/ml; and

(ii) a C max for estradiol that is from 12.9580 pg/ml to 20.2469 pg/ml.

44 . The pharmaceutical composition of claim 43 , wherein administration of the composition to the subject produces both an AUC (0-t) for estradiol that is from 280.7467 pg·hr/ml to 438.6667 pg·hr/ml, and a C max for estradiol that is from 12.9580 pg/ml to 20.2469 pg/ml.

45 . The pharmaceutical composition of claim 43 , comprising about 50 mg progesterone, wherein administration of the composition to the subject further produces, in a plasma sample from the subject, one or both parameters selected from:

(i) an AUC (0-t) for progesterone that is from 24.0174 ng·hr/ml to 37.5272 ng·hr/ml; and

(ii) a C max for progesterone that is from 17.8444 ng/ml to 27.8819 ng/ml.

46 . The pharmaceutical composition of claim 43 , comprising about 100 mg progesterone, wherein administration of the composition to the subject further produces, in a plasma sample from the subject, one or both parameters selected from:

(i) an AUC (0-t) for progesterone that is from 48.0348 ng·hr/ml to 75.0543 ng·hr/ml; and

(ii) a C max for progesterone that is from 35.6889 ng/ml to 55.7639 ng/ml.

47 . The pharmaceutical composition of claim 43 , wherein administration of the composition to the subject further produces, in a plasma sample from the subject, one or both parameters selected from:

(i) an AUC (0-t) for estrone that is from 1819.2181 pg·hr/ml to 2842.5283 pg·hr/ml; and

(ii) a C max for estrone that is from 85.3098 pg/ml to 133.2966 pg/ml.

48 . The pharmaceutical composition of claim 43 , wherein administration of the composition to the subject further produces, in a plasma sample from the subject, one or both parameters selected from:

(i) an AUC (0-t) for total estrone that is from 40.3505 ng·hr/ml to 63.0476 ng·hr/ml; and

(ii) a C max for total estrone that is from 7.0858 ng/ml to 11.0715 ng/ml.

49 . A method for treating a human female subject having a vasomotor symptom associated with estrogen deficiency, the method comprising administering to the subject a pharmaceutical composition of claim 43 , wherein the pharmaceutical composition is administered to the subject once daily for at least one month.

50 . A pharmaceutical composition for administering estradiol and progesterone to a human female subject having a vasomotor symptom associated with estrogen deficiency comprising:

about 1.0 mg estradiol,

progesterone, and

a solubilizing agent, the solubilizing agent comprising a C6-C12 oil,

wherein the estradiol and the progesterone are present in the solubilizing agent, and at least 80% of the estradiol is solubilized; and

wherein administration of the composition to the subject produces, in a plasma sample from the subject, one or both parameters selected from:

(i) an area under the curve (AUC) (0-t) for estradiol that is from 561.4933 pg·hr/ml to 877.3333 pg·hr/ml; and

(ii) a C max for estradiol that is from 25.9161 pg/ml to 40.4939 pg/ml.

51 . The pharmaceutical composition of claim 50 , wherein administration of the composition to the subject produces both an AUC (0-t) for estradiol that is from 561.4933 pg·hr/ml to 877.3333 pg·hr/ml, and a C max for estradiol that is from 25.9161 pg/ml to 40.4939 pg/ml.

52 . The pharmaceutical composition of claim 50 , further comprising 100 mg progesterone, wherein administration of the composition to the subject further produces, in a plasma sample from the subject, one or both parameters selected from:

(i) an AUC (0-t) for progesterone that is from 48.0348 ng·hr/ml to 75.0543 ng·hr/ml; and

(ii) and a C max for progesterone that is from 35.6889 ng/ml to 55.7639 ng/ml.

53 . The pharmaceutical composition of claim 50 , wherein administration of the composition to the subject further produces, in a plasma sample from the subject, one or both parameters selected from:

(i) an AUC (0-t) for estrone that is from 3638.4363 pg·hr/ml to 5685.0567 pg·hr/ml; and

(ii) a C max for estrone that is from 170.6197 pg/ml to 266.5933 pg/ml.

54 . The pharmaceutical composition of claim 50 , wherein administration of the composition to the subject further produces, in a plasma sample from the subject, one or both parameters selected from:

(i) an AUC (0-t) for total estrone that is from 80.7010 ng·hr/ml to 126.0953 ng·hr/ml; and

(ii) a C max for total estrone that is from 14.1716 ng/ml to 22.1431 ng/ml.

55 . A method for treating a human female subject having a vasomotor symptom associated with estrogen deficiency, the method comprising administering to the subject a pharmaceutical composition of claim 50 , wherein the pharmaceutical composition is administered to the subject once daily for at least one month