Natural combination hormone replacement formulations and therapies
Estrogen and progesterone replacement therapies are provided herein. Among others, the following formulations are provided herein: solubilized estradiol without progesterone; micronized progesterone without estradiol; micronized progesterone with partially solubilized progesterone; solubilized estradiol with micronized progesterone; solubilized estradiol with micronized progesterone in combination with partially solubilized progesterone; and solubilized estradiol with solubilized progesterone.
1. A method of treating an estrogen-deficient state in a female subject in need of treatment, the method comprising administering to the subject a capsule containing an effective amount of a pharmaceutical formulation comprising:
0.17 to 0.35 wt % solubilized estradiol,
30 to 35 wt % progesterone, comprising suspended micronized progesterone and solubilized progesterone,
55 to 75 wt % of an oil, wherein the oil is predominantly medium chain fatty acid mono- and diglycerides comprising esters of C6 to C12 fatty acids, and
0.5 to 10 wt % nonionic surfactant;
wherein the solubilized estradiol, the suspended micronized progesterone, and the solubilized progesterone are present in the oil.
2. The method of claim 1 , wherein the oil is predominantly medium chain fatty acid mono- and diglycerides comprising esters of C6 to C10 fatty acids.
3. The method of claim 1 , wherein the oil is predominantly medium chain fatty acid mono- and diglycerides comprising esters of C8 to C12 fatty acids.
4. The method of claim 1 , wherein the oil is predominantly medium chain fatty acid mono- and diglycerides comprising esters of C8 to C10 fatty acids.
5. The method of claim 1 , wherein at least 90% of the total estradiol is solubilized.
6. The method of claim 1 , wherein the non-ionic surfactant is lauroyl polyoxyl-32-glycerides.
7. The method of claim 1 wherein the capsule is a gelatin capsule.
8. The method of claim 1 , wherein the progesterone is released more rapidly from the pharmaceutical composition than progesterone in peanut oil.
9. The method of claim 1 , wherein the estrogen-deficient state is selected from the group consisting of a vasomotor symptom of menopause, sleep disturbances, mood changes, vulvovaginal atrophy, and osteoporosis.
10. The method of claim 1 , wherein the estrogen-deficient state is a vasomotor symptom of menopause.
11. The method of claim 1 , wherein the vasomotor symptom of menopause is selected from the group consisting of hot flashes and night sweats.
12. The method of claim 1 , wherein the female subject is a post-menopausal woman.
13. A method of treating a vasomotor symptom of menopause in a female subject in need of treatment, the method comprising administering to the subject a capsule containing an effective amount of a pharmaceutical formulation comprising:
0.17 to 0.35 wt % solubilized estradiol,
30 to 35 wt % progesterone, comprising suspended micronized progesterone and solubilized progesterone,
55 to 75 wt % of an oil, wherein the oil is predominantly medium chain fatty acid mono- and diglycerides comprising predominantly esters of C6 to C12 fatty acids, and
0.5 to 10 wt % nonionic surfactant;
wherein the solubilized estradiol, the suspended micronized progesterone, and the solubilized progesterone are present in the oil.
14. The method of claim 13 , wherein the vasomotor symptom of menopause is selected from the group consisting of hot flashes and night sweats.
15. The method of claim 13 , wherein the mammal is a post-menopausal woman.
16. A method of treating vulvovaginal atrophy in a female subject in need of treatment, the method comprising administering to the subject a capsule containing an effective amount of a pharmaceutical formulation comprising:
0.17 to 0.35 wt % solubilized estradiol,
30 to 35 wt % progesterone, comprising suspended micronized progesterone and solubilized progesterone,
55 to 75 wt % of an oil, wherein the oil is predominantly medium chain fatty acid mono- and diglycerides comprising predominantly esters of C6 to C12 fatty acids, and
0.5 to 10 wt % nonionic surfactant;
wherein the solubilized estradiol, the suspended micronized progesterone, and the solubilized progesterone are present in the oil.