Low Dose Estrogen Interrupted Hormone Replacement Therapy

Abstract

A hormone replacement therapy, comprising a plurality of daily doses of a pharmaceutical preparation, the doses being administered continuously and consecutively in alternating phases of three daily doses, a relatively dominant estrogenic activity phase comprising three daily doses of a substance exhibiting estrogenic activity equivalent to about 1 mg per day of 17β-estradiol per day, and a relatively dominant progestagenic activity phase of a combination of a substance exhibiting estrogenic activity equivalent to about 1 mg per day of 17β-estradiol and a substance exhibiting progestogenic activity equivalent to about 90 μg per day of norgestimate.

1 - 34 . (canceled) 
     
     
         35 . A method of enhancing estrogenic activity in a female in need thereof, the method comprising administering to the female:
 (a) three consecutive daily dosage forms or an equivalent thereof comprising a substance exhibiting estrogenic activity; followed by   (b) three consecutive daily dosage forms or an equivalent thereof comprising a substance exhibiting estrogenic activity and a substance exhibiting progestogenic activity equivalent to about 90 μg norgestimate per day,   
       wherein estrogenic activity is enhanced in the female in need thereof. 
     
     
         36 . The method of  claim 35 , wherein the enhancement of estrogenic activity reduces hot flashes. 
     
     
         37 . The method of  claim 35 , wherein the enhancement of estrogenic activity increases the expression of an estrogen-induced lipoprotein selected from the group consisting of HDL, HDL-2, and combinations thereof. 
     
     
         38 . The method of  claim 35 , wherein the method further comprises administering a placebo, an iron supplement, a vitamin supplement, or a combination thereof. 
     
     
         39 . The method of  claim 35 , wherein the dosage forms are administered orally, parenterally, transdermally, transmucosally, intramuscularly, or intravaginally. 
     
     
         40 . The method of  claim 39 , wherein the dosage forms are in an oral dosage form. 
     
     
         41 . The method of  claim 40 , wherein the oral dosage form is a tablet. 
     
     
         42 . A pharmaceutical composition for enhancing estrogenic activity in a female in need thereof, the composition comprising:
 (a) three consecutive daily dosage forms or an equivalent thereof comprising a substance exhibiting estrogenic activity; and   (b) three consecutive daily dosage forms or an equivalent thereof comprising a substance exhibiting estrogenic activity and a substance exhibiting progestogenic activity equivalent to about 90 μg norgestimate per day.   
     
     
         43 . The composition of  claim 42 , wherein the substance exhibiting estrogenic activity comprises 17α-ethinylestradiol, esters or ethers of 17α-ethinylestradiol, 17α-ethinylestradiol 3-dimethylamino propionate, 17α-ethinylestradiol 3-cyclopentyl ether (quienestrol), or 17α-ethinylestradiol 3-methyl ether (mestranol); natural estrogens, estrone, estrone sulfate, estrone sulfate piperazine salt, estradiol, estriol, or their esters; synthetic estrogens; or a combination thereof, and wherein the substance exhibiting progestogenic activity comprises desogestrel, dydrogesterone, medroxyprogesterone acetate, norethynodrel, cyproterone acetate, chlormadinone acetate, magestrol acetate, 17 D-acetyl norgestimate, dienogest, trimegestone, drosperinone, nomagestrel, or a combination thereof. 
     
     
         44 . The composition of  claim 42 , wherein the composition further comprises a placebo, an iron supplement, a vitamin supplement, or a combination thereof. 
     
     
         45 . The composition of  claim 42 , wherein the dosage forms are administered orally, parenterally, transdermally, transmucosally, intramuscularly, or intravaginally. 
     
     
         46 . The composition of  claim 45 , wherein the dosage forms are in an oral dosage form. 
     
     
         47 . The composition of  claim 46 , wherein the oral dosage form is a tablet. 
     
     
         48 . A method of reducing heart disease in a female, the method comprising alternatively administering to a female in need thereof:
 (a) an estrogen dominant phase comprising administering a dosage form comprising a substance exhibiting estrogenic activity for three days; and   (b) a progestin dominant phase comprising administering a dosage form comprising a substance exhibiting estrogenic activity and a substance exhibiting progestogenic activity equivalent to about 90 μg norgestimate for three days,   
       wherein the method causes an increase in the expression of an estrogen-induced lipoprotein. 
     
     
         49 . The method of  claim 48 , wherein the method further comprises administering a placebo, an iron supplement, a vitamin supplement, or a combination thereof. 
     
     
         50 . The method of  claim 48 , wherein the dosage forms are administered orally, parenterally, transdermally, transmucosally, intramuscularly, or intravaginally. 
     
     
         51 . The method of  claim 50 , wherein the dosage forms are in an oral dosage form. 
     
     
         52 . The method of  claim 51 , wherein the oral dosage form is a tablet. 
     
     
         53 . A method of preventing osteoporosis in a female, the method comprising alternatively administering to a female in need thereof:
 (a) an estrogen dominant phase comprising administering a dosage form comprising a substance exhibiting estrogenic activity for three days; and   (b) a progestin dominant phase comprising administering a dosage form comprising a substance exhibiting estrogenic activity and a substance exhibiting progestogenic activity equivalent to about 90 μg norgestimate for three days.   
     
     
         54 . The method of  claim 53 , wherein the method further comprises administering a placebo, an iron supplement, a vitamin supplement, or a combination thereof. 
     
     
         55 . The method of  claim 53 , wherein the dosage forms are administered orally, parenterally, transdermally, transmucosally, intramuscularly, or intravaginally. 
     
     
         56 . The method of  claim 55 , wherein the dosage forms are in an oral dosage form. 
     
     
         57 . The method of  claim 56 , wherein the oral dosage form is a tablet. 
     
     
         58 . A method of preventing Alzheimer's disease in a female, the method comprising alternatively administering to a female in need thereof:
 (a) an estrogen dominant phase comprising administering a dosage form comprising a substance exhibiting estrogenic activity for three days; and   (b) a progestin dominant phase comprising administering a dosage form comprising a substance exhibiting estrogenic activity and a substance exhibiting progestogenic activity equivalent to about 90 μg norgestimate for three days.   
     
     
         59 . The method of  claim 58 , wherein the method further comprises administering a placebo, an iron supplement, a vitamin supplement, or a combination thereof. 
     
     
         60 . The method of  claim 58 , wherein the dosage forms are administered orally, parenterally, transdermally, transmucosally, intramuscularly, or intravaginally. 
     
     
         61 . The method of  claim 60 , wherein the dosage forms are in an oral dosage form. 
     
     
         62 . The method of  claim 61 , wherein the oral dosage form is a tablet.