NATURAL COMBINATION HORMONE REPLACEMENT FORMULATIONS AND THERAPIES
Pharmaceutical compositions for co-administering estradiol and progesterone to a human subject having vasomotor symptoms associated with estrogen deficiency are provided. In some embodiments, the pharmaceutical composition produces certain pharmacokinetic parameters when the composition is administered to the subject.
1 . A pharmaceutical composition for co-administering estradiol and progesterone to a human subject having vasomotor symptoms associated with estrogen deficiency comprising: 1 mg of estradiol and 100 mg of progesterone;
wherein administration of the composition to the subject produces, in a serum sample from the subject, one or more pharmacokinetic parameters selected from:
(i) a steady state estradiol concentration that is from 42.29 pg/mL to 45.58 pg/mL;
(ii) a steady state estrone concentration that is from 213.79 pg/mL to 241.57 pg/mL; and
(iii) a steady state progesterone concentration that is from 386.53 pg/mL to 547.83 pg/mL.
2 . The pharmaceutical composition of claim 1 , wherein administration of the composition to the subject produces a steady state estradiol concentration that is from 42.29 pg/mL to 45.58 pg/mL.
3 . (canceled)
4 . The pharmaceutical composition of claim 1 , wherein administration of the composition to the subject produces both a steady state estradiol concentration that is from 42.29 pg/mL to 45.58 pg/mL and a steady state progesterone concentration that is from 386.53 pg/mL to 547.83 pg/mL.
5 . (canceled)
6 . A pharmaceutical composition for co-administering estradiol and progesterone to a human subject having vasomotor symptoms associated with estrogen deficiency comprising: 0.5 mg of estradiol and 100 mg of progesterone;
wherein administration of the composition to the subject produces, in a serum sample from the subject, one or more pharmacokinetic parameters selected from:
(i) a steady state estradiol concentration that is from 23.03 pg/mL to 27.37 pg/mL;
(ii) a steady state estrone concentration that is from 113.59 pg/mL to 132.08 pg/mL; and
(iii) a steady state progesterone concentration that is from 386.53 pg/mL to 547.83 pg/mL.
7 . The pharmaceutical composition of claim 6 , wherein administration of the composition to the subject produces a steady state estradiol concentration that is from 23.03 pg/mL to 27.37 pg/mL.
8 . (canceled)
9 . The pharmaceutical composition of claim 6 , wherein administration of the composition to the subject produces both a steady state estradiol concentration that is from 23.03 pg/mL to 27.37 pg/mL and a steady state progesterone concentration that is from 386.53 pg/mL to 547.83 pg/mL.
10 . (canceled)
11 . A pharmaceutical composition for co-administering estradiol and progesterone to a human subject having vasomotor symptoms associated with estrogen deficiency comprising: 0.5 mg of estradiol and 50 mg of progesterone;
wherein administration of the composition to the subject produces, in a serum sample from the subject, one or more pharmacokinetic parameters selected from:
(i) a steady state estradiol concentration that is from 23.03 pg/mL to 27.37 pg/mL;
(ii) a steady state estrone concentration that is from 113.59 pg/mL to 132.08 pg/mL; and
(iii) a steady state progesterone concentration that is from 181.41 pg/mL to 247.17 pg/mL.
12 . The pharmaceutical composition of claim 11 , wherein administration of the composition to the subject produces a steady state estradiol concentration that is from 23.03 pg/mL to 27.37 pg/mL.
13 . (canceled)
14 . The pharmaceutical composition of claim 11 , wherein administration of the composition to the subject produces both a steady state estradiol concentration that is from 23.03 pg/mL to 27.37 pg/mL and a steady state progesterone concentration that is from 181.41 pg/mL to 247.17 pg/mL.
15 . (canceled)
16 . A pharmaceutical composition for co-administering estradiol and progesterone to a human subject having vasomotor symptoms associated with estrogen deficiency comprising: 0.25 mg of estradiol and 50 mg of progesterone;
wherein administration of the composition to the subject produces, in a serum sample from the subject, one or more pharmacokinetic parameters selected from:
(i) a steady state estradiol concentration that is from 15.06 pg/mL to 18.50 pg/mL;
(ii) a steady state estrone concentration that is from 69.02 pg/mL to 73.43 pg/mL; and
(iii) a steady state progesterone concentration that is from 181.41 pg/mL to 247.17 pg/mL.
17 . The pharmaceutical composition of claim 16 , wherein administration of the composition to the subject produces a steady state estradiol concentration that is from 15.06 pg/mL to 18.50 pg/mL.
18 . (canceled)
19 . The pharmaceutical composition of claim 16 , wherein administration of the composition to the subject produces both a steady state estradiol concentration that is from 15.06 pg/mL to 18.50 pg/mL and a steady state progesterone concentration that is from 181.41 pg/mL to 247.17 pg/mL.
20 . (canceled)
21 . The pharmaceutical composition of claim 1 , wherein composition further comprises a solubilizing agent.
22 . The pharmaceutical composition of claim 21 , wherein the solubilizing agent comprises a medium chain (C6-C12) oil.
23 . (canceled)
24 . The pharmaceutical composition of claim 1 , wherein the estradiol is solubilized estradiol.
25 . (canceled)
26 . The pharmaceutical composition of claim 1 , wherein the progesterone is suspended progesterone.
27 - 28 . (canceled)
29 . The pharmaceutical composition of claim 1 , wherein administration of the composition to the subject further produces in the subject a reduction in the frequency and/or severity of one or more symptoms of menopause.
30 - 32 . (canceled)
33 . A method of treating a subject having vasomotor symptoms associated with estrogen deficiency, the method comprising administering to the subject an effective amount of the pharmaceutical composition of claim 1 .
34 . The method of claim 33 , wherein the subject is female.
35 . (canceled)
36 . The method of claim 33 , wherein prior to treatment, the subject has a serum estradiol of ≤10 pg/mL.
37 . (canceled)