US3795734A - Cyclic regimen of hormone administration for contraception - Google Patents
Cyclic regimen of hormone administration for contraception Download PDFInfo
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- US3795734A US3795734A US00030302A US3795734DA US3795734A US 3795734 A US3795734 A US 3795734A US 00030302 A US00030302 A US 00030302A US 3795734D A US3795734D A US 3795734DA US 3795734 A US3795734 A US 3795734A
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- progestin
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- estrogen
- regimen
- cycle
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/565—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/57—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
Definitions
- Sequentialestrogen is administered alone from day 5, either for 15 or 11 days, a progestin is then added for another 5 to days, respectively, to induce withdrawal bleeding.
- -It is the object of this invention to disclose a new contraceptive regimen, which is effective, well-tolerated and substantially free from the side effects associated with either the currently available estrogen-progestin regimens or the newer progestin alone approaches.
- the present invention relates to a new therapeutic regimen which provides contraception and regulation of the menstrual cycle.
- the regimen of this invention involves the administering of consecutive daily dosages of a progestin during the early phase of the cycle followed by consecutive daily dosages of an estrogen-progestin combination during the midcycle, followed by consecutive daily dosages of a progestin during the final phase of the cycle.
- a reliable oral contraceptive regimen comprising the administration of la progestin alone with a minimal supplemental estrogen reinforcement at a critical period of the menstrual cycle.
- the regimen is tolerated as well as the progestin alone regimens and overcomes the high incidences of breakthrough bleeding and irregular cycling.
- an important aspect of this regimen is that it allows a normal or near normal endometrial morphology by supplying sufiicient estrogen at a critical period of the cycle, namely at the early part of the midcycle.
- supplemental estrogen By using this regimen with supplemental estrogen at this critical period, sufficient estrogen is available for development of a proliferative endometrium and subsequent support of the endometrium as it crosses from a proliferative phase to a secretory phase.
- the present regimen allows an endometrial morphology similar to the natural, menstruation follows regularly after withdrawal of the medication in the final phase of the cycle.
- Another important aspect of this invention is that only a minimal amount of estrogen is employed. Consequently, the side effects associated with the administration of large dosages of estrogens to women of child bearing age are avoided.
- a menstrual cycle of 28 days is assumed.
- the cycle is considered to be divided into four phases.
- Day 1 is the first day of menstrual bleeding of the first medicated cycle.
- days 1, 2, 3, and 4 are medication free.
- phase II begins.
- a pro- 11 to inclusive medication is combined estrogen-progestin.
- phase I V'begins.
- days 16 to 26 in elusive medication reverts to progestin alone.
- Phase I then begins anew with no medication for days 27, 28, 1, 2, 3 and 4 inclusive. (Alternatively, placebo treatment could be given during the phase I periods, to effect continuous pill-taking and by-pass possible patient failures.)
- phase III may range from days 12 to 14 inclusive (three days) to days 10 to 16 inclusive (seven days).
- suitable estrogens or progestins for use in this regimen also is not critical provided that they have proven therapeutic utility.
- suitable estrogens include 170a [3 furyl] estra-1,3,5(10),7-tetraene-3,17- diol S-acetate, ethynyl estradiol, mestranol and equilin sulfate.
- suitable progestins include medrogestone, ethisterone, norethindrone and clogestanone acetate. Examples of these and other suitable estrogens and progestins are described in the literature; for example, U. Banik 'et al., J. Reprod. FertiL, 18, 509 (1969), C. Dodds, Clin. Pharmacol. Therap., 10, 147 (1969) and E. Diczfalusy, Am. J. Obstet. Gynecol., 100, 136 (1968).
- each of the aforenamed estrogen or progestin possesses its own particular degree of efiectiveness and has certain advantages over the others so that a particular estrogen or progestin to be used in a particular regimen of this invention will depend on the specific needs of the patient.
- Examples of daily dosages that may be used for this regimen are, for the estrogens, 0.01-0.1 mg./day/patient for 170: [3 furyl] estra-1,3,5(l0),7-tetraene-3,17diol and 0.1 to 0.5 mg./day 3-acetate, ethynyl estradiol, or mestranol; patient for equilin sulfate; and for the progestins mentioned above 0.5 to 3.0 mg./day/patient.
- estrogens and progestins may be administered orally in solid dosage forms such as, for example, tablets, capsules, or the like.
- solid dosage forms such as, for example, tablets, capsules, or the like.
- the regimen calls for administration of both estrogen and progestin tablets, capsules or the like may be formulated containing both those hormones.
- the hormones are compounded with inert pharmaceutical carriers;
- I claim? 1 In a method of providing contraception and regulation of the menstrual cycle wherein estrogen and progestin hormones are administered to women during their menstrual cycle, the improvement which comprises: (a) administering orally, consecutive daily doses of a progestin in an oral daily dosage amount of 0.05
- said specified dosages of estrogen and progestin being the only estrogens and progestins administered during said menstrual cycle.
- estrogen selected from the class consisting of 17a- [3 furyl] estra 1,3,5 (10),7-tetraene-3,17-diol 3- acetate, ethynyl estradiol, mestranol and equilin sulfate in an oral daily dosage amount of 0.01 to 0.10 milligram per day for a duration of three to seven days within the tenth to the 16th day of said menstrual cycle,
- estrogen and progestin being the References Cited Physicians Desk Reference,- 22nd ed., published by Medical Economics, Inc, Oradell, N.J., 1967, pp. 1064- 1067.
- Examples of dailyvdosages that may be used for this regimen are, for the estrogens, O-.Ol-O.l mg./da,y/patient for 17oL-[3-furyl1 -estra.-l,3,5,(10),7-tetraene-3,l7-dio1 3'- acetate, ethynyl estradiol, or mestranol; and. 0.1-0.5 mg./day/patient for equilin sulfate; and. for the progestins mentioned above, 0. 5 to 3.0 mg.,/d.ay pa.tient.
Abstract
THE IS DISCLOSED HEREIN A METHOD OF ADMINISTERING HORMONES FOR PROVIDING CONTRACEPTION AND REGULATION OF THE MENSTRUAL CYCLE WHEREIN CONSECUTIVE DAILY DOSAGES OF A PROGESTIN ARE GIVEN DURING THE EARLY PHASE OF THE CYCLE, CONSECUTIVE DAILY DOSES OF AN ESTROGEN-PROGESTIN COMBINATION ARE GIVEN DURING THE MIDCYCLE AND CONSECUTIVE DAILY DOSAGES OF A PROGESTIN ARE GIVEN DURING THE FINAL PHASE OF THE CYCLE.
Description
United States Patent 3,795,734 CYCLIC REGIMEN F HORMONE ADMINISTRA- TION FOR CONTRACEPTION Joseph Guy Rochefort, St. Laurent, Quebec, Canada, as-
siguor to American Home Products Corporation, New York, N.Y. No Drawing. Filed Apr. 20, 1970, Ser. No. 30,302
- Int. Cl. A61k 17/06 US. Cl. 424-238 2 Claims ABSTRACT OF THE DISCLOSURE There is disclosed herein a method of administering hormones for providing contraception and regulation of the menstrual cycle wherein consecutive daily dosages of a progestin are given during the early [phase of the cycle, consecutive daily doses of an estrogen-progestin combination are given during the midcycle and consecutive daily dosages of a progestin are given during the final phase of the cycle.
BACKGROUND OF THE INVENTION Two therapeutic regimens are in general use for the present day estrogen-progestin contraceptives:
(1) Combinedthe estrogen and progestin are administered together Starting on day of the menstrual cycle. Day 1 is designated as the first day of menstrual bleeding. Medication is continued until day 25 or day 26. Normally menstruation occurs three to five days thereafter.
(2) Sequentialestrogen is administered alone from day 5, either for 15 or 11 days, a progestin is then added for another 5 to days, respectively, to induce withdrawal bleeding.
Notwithstanding the relative Wide acceptance of these regimens, adverse reactions are continually being reported for them in both the scientific literature and the lay press. A comprehensive report with leading references on the complications associated with these regimens can be found in the Second Report on Oral Contraceptives, Advisory Committee on Obstetrics and Gynecology, to the Food and Drug Administration, US. Govt. Printing Ofiice, Washington, DC, August 1, 1969.
In view of the recognized risks and side elfects of the present combined oral contraceptives, an intense effort has been mounted to develop contraceptives with reduced side effects while maintaining maximal efficacy. The most promising approaches in this direction include the use of progestin alone therapy by either oral administration, such as the continuous low dosage of a progestin regimen, or parenteral administration, such as depot injection or implantation of a progestin-filled silicone rubber implant, Second Report on Oral Contraceptives, cited above, pp. 16-17.
Side elfects associated with the estrogen-progestin regimens, such as nausea, weight gain, headaches and risk of thromboembolic problems, appear to be significantly reduced, rendering these progestin alone regimens better 3,795,734 Patented Mar. 5, 1974 irregular bleeding will make these progestin alone regimens unacceptable to most women, J. dA. Jefiery and A. I. Klopper, J. Reprod. Fert., Suppl, 4, 81 (1968) and Brit. Med. J., 4, 286 (1969).
-It is the object of this invention to disclose a new contraceptive regimen, which is effective, well-tolerated and substantially free from the side effects associated with either the currently available estrogen-progestin regimens or the newer progestin alone approaches.
SUMMARY OF THE INVENTION- The present invention relates to a new therapeutic regimen which provides contraception and regulation of the menstrual cycle.
More particularly, the regimen of this invention involves the administering of consecutive daily dosages of a progestin during the early phase of the cycle followed by consecutive daily dosages of an estrogen-progestin combination during the midcycle, followed by consecutive daily dosages of a progestin during the final phase of the cycle.
DETAILS OF THE INVENTION The intense effort to develop new techniques of contraception are attempts to escape from the multiple administrations of estrogen and combined estrogen-progestin and the side effects thereof, such as nausea, headache, weight .gain and increased risk of thromboembolic problems.
As noted above, even the most promising of the newer techniques, those involving progestin alone approaches have serious disadvantages of another kind, such as irregular bleeding and cycling.
Our present knowledge does not allow us to explain the reasons for these disadvantages. Clinical observations to date, however, point to the fact that the progestin alone regimens impede endometrial growth, J. Martinez- Manautou et al., Fertil. Steril., 17, 49 (1966) and references therein. A direct consequence of this impediment of growth, I believe, is the high incidences of breakthrough bleeding and irregular cycling.
I have now developed a reliable oral contraceptive regimen, comprising the administration of la progestin alone with a minimal supplemental estrogen reinforcement at a critical period of the menstrual cycle. The regimen is tolerated as well as the progestin alone regimens and overcomes the high incidences of breakthrough bleeding and irregular cycling. Indeed, an important aspect of this regimen is that it allows a normal or near normal endometrial morphology by supplying sufiicient estrogen at a critical period of the cycle, namely at the early part of the midcycle. By using this regimen with supplemental estrogen at this critical period, sufficient estrogen is available for development of a proliferative endometrium and subsequent support of the endometrium as it crosses from a proliferative phase to a secretory phase. Furthermore, since the present regimen allows an endometrial morphology similar to the natural, menstruation follows regularly after withdrawal of the medication in the final phase of the cycle.
Another important aspect of this invention is that only a minimal amount of estrogen is employed. Consequently, the side effects associated with the administration of large dosages of estrogens to women of child bearing age are avoided.
A preferred embodiment of the present invention is illustrated by the following regimen:
For the purpose of describing this embodiment a menstrual cycle of 28 days is assumed. The cycle is considered to be divided into four phases. Day 1 is the first day of menstrual bleeding of the first medicated cycle. In the first phase, days 1, 2, 3, and 4 are medication free. On
day 5, phase II begins. For' days 5 to inclusive, a pro- 11 to inclusive, medication is combined estrogen-progestin. On day 16, phase I V'begins. For days 16 to 26 in elusive, medication reverts to progestin alone. Phase I then begins anew with no medication for days 27, 28, 1, 2, 3 and 4 inclusive. (Alternatively, placebo treatment could be given during the phase I periods, to effect continuous pill-taking and by-pass possible patient failures.)
The actual duration of the various phases is not critical in that both days limiting their duration may be varied a day earlier or later. In other words, phase III may range from days 12 to 14 inclusive (three days) to days 10 to 16 inclusive (seven days).
The choice of suitable estrogens or progestins for use in this regimen also is not critical provided that they have proven therapeutic utility. Examples of suitable estrogens include 170a [3 furyl] estra-1,3,5(10),7-tetraene-3,17- diol S-acetate, ethynyl estradiol, mestranol and equilin sulfate. Examples of suitable progestins include medrogestone, ethisterone, norethindrone and clogestanone acetate. Examples of these and other suitable estrogens and progestins are described in the literature; for example, U. Banik 'et al., J. Reprod. FertiL, 18, 509 (1969), C. Dodds, Clin. Pharmacol. Therap., 10, 147 (1969) and E. Diczfalusy, Am. J. Obstet. Gynecol., 100, 136 (1968).
'Each of the aforenamed estrogen or progestin possesses its own particular degree of efiectiveness and has certain advantages over the others so that a particular estrogen or progestin to be used in a particular regimen of this invention will depend on the specific needs of the patient. Examples of daily dosages that may be used for this regimen are, for the estrogens, 0.01-0.1 mg./day/patient for 170: [3 furyl] estra-1,3,5(l0),7-tetraene-3,17diol and 0.1 to 0.5 mg./day 3-acetate, ethynyl estradiol, or mestranol; patient for equilin sulfate; and for the progestins mentioned above 0.5 to 3.0 mg./day/patient.
The above estrogens and progestins may be administered orally in solid dosage forms such as, for example, tablets, capsules, or the like. For those days when the regimen calls for administration of both estrogen and progestin tablets, capsules or the like may be formulated containing both those hormones. In tablet form the hormones are compounded with inert pharmaceutical carriers;
It is apparent that many variations may be'made in the" construction of the present embodiment of this invention without departing from the spirit of this invention. Such variations are intended to be included within the scope of this invention.
" I claim? 1. In a method of providing contraception and regulation of the menstrual cycle wherein estrogen and progestin hormones are administered to women during their menstrual cycle, the improvement which comprises: (a) administering orally, consecutive daily doses of a progestin in an oral daily dosage amount of 0.05
to 3.0 milligrams per day from the fifth day to the 26th day of said menstrual cycle after the first day of menstrual bleeding; and
(b) administering orally, consecutive daily doses of estrogen in an oral daily dosage amount of 0.01 to 0.10 milligram per day fona duration of three to seven. days within the tenth to-the 16th day of said menstrual cycle,
said specified dosages of estrogen and progestin being the only estrogens and progestins administered during said menstrual cycle.
2. In a method of providing contraception and regulation of the menstrual cycle wherein estrogen and progestin hormones are administered to women during their menstrual cycle, the improvement which comprises:
(a) administering orally, consecutive daily doses of progestin selected from the class consisting of medrogestone, e'thisterone, norethindrone and clogestanone acetate in an oral daily dosage amount of 0.5 to 3.0 milligrams per day from the fifth day to the 26th day of said menstrual cycle after the first day of menstrual bleeding; and
(b) administering orally, consecutive daily doses of estrogen selected from the class consisting of 17a- [3 furyl] estra 1,3,5 (10),7-tetraene-3,17-diol 3- acetate, ethynyl estradiol, mestranol and equilin sulfate in an oral daily dosage amount of 0.01 to 0.10 milligram per day for a duration of three to seven days within the tenth to the 16th day of said menstrual cycle,
said specified dosages of estrogen and progestin being the References Cited Physicians Desk Reference,- 22nd ed., published by Medical Economics, Inc, Oradell, N.J., 1967, pp. 1064- 1067.
RICHARD L.,HUFF, Primary Examiner US. Cl. X.R. 4424l, 242, 243
333 v UNITED STATES PATENT OFFICE CERTIFICATE OF CORRECTION Patent -a'mmvsu Dated March 5, 1 7? In nwfl Di. Rochefort It is certified that error appears in the above-identified patent and that said Letters 'Patent are hereby corrected as shown below:
The sentence starting at Column 3, line 32, should. readcorrectly as follows:
"Examples of dailyvdosages that may be used for this regimen are, for the estrogens, O-.Ol-O.l mg./da,y/patient for 17oL-[3-furyl1 -estra.-l,3,5,(10),7-tetraene-3,l7-dio1 3'- acetate, ethynyl estradiol, or mestranol; and. 0.1-0.5 mg./day/patient for equilin sulfate; and. for the progestins mentioned above, 0. 5 to 3.0 mg.,/d.ay pa.tient.
Signed and sealed this 17th day of September 1974.
(SEAL) Attest: V
McCOY M. GIBSON JR. o c. MARSHALL DANN o Attesting Officer 7 Commissioner of Patents
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US3030270A | 1970-04-20 | 1970-04-20 |
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| Publication Number | Publication Date |
|---|---|
| US3795734A true US3795734A (en) | 1974-03-05 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| US00030302A Expired - Lifetime US3795734A (en) | 1970-04-20 | 1970-04-20 | Cyclic regimen of hormone administration for contraception |
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| US (1) | US3795734A (en) |
Cited By (21)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3892855A (en) * | 1973-10-10 | 1975-07-01 | Searle & Co | Method for fertile breeding control in female bovine |
| US3939264A (en) * | 1972-04-14 | 1976-02-17 | Schering Aktiengesellschaft | Method for contraception by the administration of sequential contraceptive preparations |
| US3957982A (en) * | 1973-12-21 | 1976-05-18 | Schering Aktiengesellschaft | Method for contraception by the application of combination-type sequential preparations |
| US4018919A (en) * | 1975-07-16 | 1977-04-19 | Eli Lilly And Company | Sequential contraceptive method using two types of progestational agents |
| US4143136A (en) * | 1976-11-20 | 1979-03-06 | Akzona Incorporated | Method of contraception |
| DE3229612A1 (en) * | 1981-08-10 | 1983-02-24 | Syntex (U.S.A.) Inc., 94304 Palo Alto, Calif. | PHARMACEUTICAL PACK |
| US4610687A (en) * | 1984-08-06 | 1986-09-09 | Board Of Trustees Operating Michigan State University | Method for breeding control in female bovines |
| US5010070A (en) * | 1987-06-15 | 1991-04-23 | Warner-Lambert Company | Graduated estrogen contraceptive |
| US5108995A (en) * | 1987-09-24 | 1992-04-28 | Jencap Research Ltd. | Hormone preparation and method |
| US5276022A (en) * | 1987-09-24 | 1994-01-04 | Jencap Research Ltd. | Hormone preparation and method |
| US20030207855A1 (en) * | 2000-03-10 | 2003-11-06 | Hill Edward N. | Novel estrogenic compounds |
| US20040198670A1 (en) * | 2003-04-04 | 2004-10-07 | Hill Edward N. | Novel estrogenic compounds |
| US20040259851A1 (en) * | 2003-04-11 | 2004-12-23 | Leonard Thomas W. | Methods of administering estrogens and progestins |
| US6855703B1 (en) | 2000-03-10 | 2005-02-15 | Endeavor Pharmaceuticals | Pharmaceutical compositions of conjugated estrogens and methods of analyzing mixtures containing estrogenic compounds |
| US20050038006A1 (en) * | 1998-12-23 | 2005-02-17 | Shangold Gary A. | Triphasic oral contraceptive |
| US20060183724A1 (en) * | 2005-02-03 | 2006-08-17 | Diliberti Charles E | Compositions of unconjugated estrogens and methods for their use |
| US20070111977A1 (en) * | 2005-10-17 | 2007-05-17 | Susan Zeun | Combination preparation for oral contraception and oral therapy of dysfunctional uterine bleeding containing estradiol valerate and dienogest and method of using same |
| US20070142307A1 (en) * | 2000-03-10 | 2007-06-21 | Barr Laboratories, Inc. | Novel estrogenic compounds |
| US20070259840A1 (en) * | 2004-04-20 | 2007-11-08 | Schering Ag | Multi-Phase Contraceptive Preparation Based on a Natural Estrogen |
| US20080125401A1 (en) * | 2006-10-20 | 2008-05-29 | Susan Zeun | Use of estradiol valerate or 17beta-estradiol in combination with dienogest for oral therapy to maintain and/or increase feminine libido |
| US20100234330A1 (en) * | 2003-07-23 | 2010-09-16 | Hill Edward N | Novel Estrogenic Compounds |
-
1970
- 1970-04-20 US US00030302A patent/US3795734A/en not_active Expired - Lifetime
Cited By (33)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3939264A (en) * | 1972-04-14 | 1976-02-17 | Schering Aktiengesellschaft | Method for contraception by the administration of sequential contraceptive preparations |
| US3892855A (en) * | 1973-10-10 | 1975-07-01 | Searle & Co | Method for fertile breeding control in female bovine |
| US3957982A (en) * | 1973-12-21 | 1976-05-18 | Schering Aktiengesellschaft | Method for contraception by the application of combination-type sequential preparations |
| US4018919A (en) * | 1975-07-16 | 1977-04-19 | Eli Lilly And Company | Sequential contraceptive method using two types of progestational agents |
| US4143136A (en) * | 1976-11-20 | 1979-03-06 | Akzona Incorporated | Method of contraception |
| DE3229612A1 (en) * | 1981-08-10 | 1983-02-24 | Syntex (U.S.A.) Inc., 94304 Palo Alto, Calif. | PHARMACEUTICAL PACK |
| US4610687A (en) * | 1984-08-06 | 1986-09-09 | Board Of Trustees Operating Michigan State University | Method for breeding control in female bovines |
| US5010070A (en) * | 1987-06-15 | 1991-04-23 | Warner-Lambert Company | Graduated estrogen contraceptive |
| US5108995A (en) * | 1987-09-24 | 1992-04-28 | Jencap Research Ltd. | Hormone preparation and method |
| US5276022A (en) * | 1987-09-24 | 1994-01-04 | Jencap Research Ltd. | Hormone preparation and method |
| US20050038006A1 (en) * | 1998-12-23 | 2005-02-17 | Shangold Gary A. | Triphasic oral contraceptive |
| US20070142307A1 (en) * | 2000-03-10 | 2007-06-21 | Barr Laboratories, Inc. | Novel estrogenic compounds |
| US7179799B2 (en) | 2000-03-10 | 2007-02-20 | Barr Laboratories, Inc. | (3) and (6) substituted estrogenic compounds |
| US6660726B2 (en) | 2000-03-10 | 2003-12-09 | Endeavor Pharmaceuticals | Estrogenic compounds, pharmaceutical compositions thereof, and methods of using same |
| US6844334B2 (en) | 2000-03-10 | 2005-01-18 | Endeavor Pharmaceuticals | (3) and (6) substitued estrogenic compounds |
| US6855703B1 (en) | 2000-03-10 | 2005-02-15 | Endeavor Pharmaceuticals | Pharmaceutical compositions of conjugated estrogens and methods of analyzing mixtures containing estrogenic compounds |
| US20030207855A1 (en) * | 2000-03-10 | 2003-11-06 | Hill Edward N. | Novel estrogenic compounds |
| US8227454B2 (en) | 2000-03-10 | 2012-07-24 | Duramed Pharmaceuticals, Inc. | Estrogenic compounds, pharmaceutical compositions and formulations comprising the same |
| US7749989B2 (en) | 2000-03-10 | 2010-07-06 | Duramed Pharmaceuticals, Inc. | Estrogenic compounds, methods of using and methods of administering the same |
| US20090105198A1 (en) * | 2000-03-10 | 2009-04-23 | Duramed Pharmaceuticals, Inc. | Novel estrogenic compounds |
| US7459445B2 (en) | 2000-03-10 | 2008-12-02 | Duramed Pharmaceuticals, Inc. | Estrogenic compounds and topical pharmaceutical formulations of the same |
| US6992075B2 (en) | 2003-04-04 | 2006-01-31 | Barr Laboratories, Inc. | C(14) estrogenic compounds |
| US20040198670A1 (en) * | 2003-04-04 | 2004-10-07 | Hill Edward N. | Novel estrogenic compounds |
| US20040259851A1 (en) * | 2003-04-11 | 2004-12-23 | Leonard Thomas W. | Methods of administering estrogens and progestins |
| US20100234330A1 (en) * | 2003-07-23 | 2010-09-16 | Hill Edward N | Novel Estrogenic Compounds |
| US7989436B2 (en) | 2003-07-23 | 2011-08-02 | Duramed Pharmaceuticals, Inc. | Estrogenic compounds and pharmaceutical formulations comprising the same |
| US8071577B2 (en) | 2004-04-20 | 2011-12-06 | Bayer Pharma Aktiengesellschaft | Multi-phase contraceptive preparation based on a natural estrogen |
| US20070259840A1 (en) * | 2004-04-20 | 2007-11-08 | Schering Ag | Multi-Phase Contraceptive Preparation Based on a Natural Estrogen |
| US20060183724A1 (en) * | 2005-02-03 | 2006-08-17 | Diliberti Charles E | Compositions of unconjugated estrogens and methods for their use |
| US20070111977A1 (en) * | 2005-10-17 | 2007-05-17 | Susan Zeun | Combination preparation for oral contraception and oral therapy of dysfunctional uterine bleeding containing estradiol valerate and dienogest and method of using same |
| US8153616B2 (en) | 2005-10-17 | 2012-04-10 | Bayer Pharma Aktiengesellschaft | Combination preparation for oral contraception and oral therapy of dysfunctional uterine bleeding containing estradiol valerate and dienogest and method of using same |
| US8349820B2 (en) | 2006-10-20 | 2013-01-08 | Bayer Pharma Aktiengesellschaft | Use of estradiol valerate or 17β-estradiol in combination with dienogest for oral therapy to maintain and/or increase feminine libido |
| US20080125401A1 (en) * | 2006-10-20 | 2008-05-29 | Susan Zeun | Use of estradiol valerate or 17beta-estradiol in combination with dienogest for oral therapy to maintain and/or increase feminine libido |
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