CA2491372A1 - Infertility treatment with exemestane - Google Patents
Infertility treatment with exemestane Download PDFInfo
- Publication number
- CA2491372A1 CA2491372A1 CA002491372A CA2491372A CA2491372A1 CA 2491372 A1 CA2491372 A1 CA 2491372A1 CA 002491372 A CA002491372 A CA 002491372A CA 2491372 A CA2491372 A CA 2491372A CA 2491372 A1 CA2491372 A1 CA 2491372A1
- Authority
- CA
- Canada
- Prior art keywords
- female host
- female
- exemestane
- host
- composition
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- BFYIZQONLCFLEV-DAELLWKTSA-N Aromasine Chemical compound O=C1C=C[C@]2(C)[C@H]3CC[C@](C)(C(CC4)=O)[C@@H]4[C@@H]3CC(=C)C2=C1 BFYIZQONLCFLEV-DAELLWKTSA-N 0.000 title claims abstract description 30
- 229960000255 exemestane Drugs 0.000 title claims abstract description 30
- 208000000509 infertility Diseases 0.000 title claims abstract description 18
- 230000036512 infertility Effects 0.000 title claims abstract description 18
- 231100000535 infertility Toxicity 0.000 title claims abstract description 18
- 230000003325 follicular Effects 0.000 claims abstract description 23
- 230000002611 ovarian Effects 0.000 claims abstract description 15
- 238000000034 method Methods 0.000 claims abstract description 14
- 230000004936 stimulating effect Effects 0.000 claims abstract description 11
- 230000000638 stimulation Effects 0.000 claims description 12
- 230000001939 inductive effect Effects 0.000 claims description 8
- 239000000203 mixture Substances 0.000 claims description 8
- 201000010065 polycystic ovary syndrome Diseases 0.000 claims description 7
- 206010058359 Hypogonadism Diseases 0.000 claims description 6
- 201000003368 hypogonadotropic hypogonadism Diseases 0.000 claims description 6
- 238000004519 manufacturing process Methods 0.000 claims description 5
- 239000008194 pharmaceutical composition Substances 0.000 claims description 5
- 239000003814 drug Substances 0.000 claims description 4
- 239000003085 diluting agent Substances 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- 239000002552 dosage form Substances 0.000 claims 1
- 238000002560 therapeutic procedure Methods 0.000 abstract description 2
- 230000016087 ovulation Effects 0.000 description 8
- 102000004190 Enzymes Human genes 0.000 description 7
- 108090000790 Enzymes Proteins 0.000 description 7
- 230000027758 ovulation cycle Effects 0.000 description 6
- 102000014654 Aromatase Human genes 0.000 description 5
- 108010078554 Aromatase Proteins 0.000 description 5
- 230000006698 induction Effects 0.000 description 4
- 230000007246 mechanism Effects 0.000 description 4
- AEMFNILZOJDQLW-QAGGRKNESA-N androst-4-ene-3,17-dione Chemical compound O=C1CC[C@]2(C)[C@H]3CC[C@](C)(C(CC4)=O)[C@@H]4[C@@H]3CCC2=C1 AEMFNILZOJDQLW-QAGGRKNESA-N 0.000 description 3
- 229960005471 androstenedione Drugs 0.000 description 3
- AEMFNILZOJDQLW-UHFFFAOYSA-N androstenedione Natural products O=C1CCC2(C)C3CCC(C)(C(CC4)=O)C4C3CCC2=C1 AEMFNILZOJDQLW-UHFFFAOYSA-N 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
- 208000035475 disorder Diseases 0.000 description 3
- 230000002779 inactivation Effects 0.000 description 3
- 230000005764 inhibitory process Effects 0.000 description 3
- 201000005670 Anovulation Diseases 0.000 description 2
- 206010002659 Anovulatory cycle Diseases 0.000 description 2
- ACFIXJIJDZMPPO-NNYOXOHSSA-N NADPH Chemical compound C1=CCC(C(=O)N)=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OC[C@@H]2[C@H]([C@@H](OP(O)(O)=O)[C@@H](O2)N2C3=NC=NC(N)=C3N=C2)O)O1 ACFIXJIJDZMPPO-NNYOXOHSSA-N 0.000 description 2
- 231100000552 anovulation Toxicity 0.000 description 2
- 238000005899 aromatization reaction Methods 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 229930027945 nicotinamide-adenine dinucleotide Natural products 0.000 description 2
- 210000001672 ovary Anatomy 0.000 description 2
- 210000004681 ovum Anatomy 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- DNXHEGUUPJUMQT-UHFFFAOYSA-N (+)-estrone Natural products OC1=CC=C2C3CCC(C)(C(CC4)=O)C4C3CCC2=C1 DNXHEGUUPJUMQT-UHFFFAOYSA-N 0.000 description 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- 206010010144 Completed suicide Diseases 0.000 description 1
- 102000002004 Cytochrome P-450 Enzyme System Human genes 0.000 description 1
- 108010015742 Cytochrome P-450 Enzyme System Proteins 0.000 description 1
- 102000002322 Egg Proteins Human genes 0.000 description 1
- 108010000912 Egg Proteins Proteins 0.000 description 1
- DNXHEGUUPJUMQT-CBZIJGRNSA-N Estrone Chemical compound OC1=CC=C2[C@H]3CC[C@](C)(C(CC4)=O)[C@@H]4[C@@H]3CCC2=C1 DNXHEGUUPJUMQT-CBZIJGRNSA-N 0.000 description 1
- 102000006771 Gonadotropins Human genes 0.000 description 1
- 108010086677 Gonadotropins Proteins 0.000 description 1
- 208000034702 Multiple pregnancies Diseases 0.000 description 1
- 206010033266 Ovarian Hyperstimulation Syndrome Diseases 0.000 description 1
- 102000004451 Pituitary Gonadotropins Human genes 0.000 description 1
- 108010081865 Pituitary Gonadotropins Proteins 0.000 description 1
- 239000003098 androgen Substances 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 230000002513 anti-ovulatory effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 239000008298 dragée Substances 0.000 description 1
- 238000006911 enzymatic reaction Methods 0.000 description 1
- 239000000262 estrogen Substances 0.000 description 1
- 229960003399 estrone Drugs 0.000 description 1
- 230000004720 fertilization Effects 0.000 description 1
- 239000007941 film coated tablet Substances 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000002622 gonadotropin Substances 0.000 description 1
- 150000003278 haem Chemical group 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 208000021267 infertility disease Diseases 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 230000002427 irreversible effect Effects 0.000 description 1
- 230000035800 maturation Effects 0.000 description 1
- 238000003541 multi-stage reaction Methods 0.000 description 1
- 239000006225 natural substrate Substances 0.000 description 1
- 210000000287 oocyte Anatomy 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 230000001568 sexual effect Effects 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000007940 sugar coated tablet Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
Classifications
-
- 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
- A61K31/568—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 substituted in positions 10 and 13 by a chain having at least one carbon atom, e.g. androstanes, e.g. testosterone
- A61K31/5685—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 substituted in positions 10 and 13 by a chain having at least one carbon atom, e.g. androstanes, e.g. testosterone having an oxo group in position 17, e.g. androsterone
-
- 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
- A61K31/566—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 having an oxo group in position 17, e.g. estrone
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/08—Drugs for genital or sexual disorders; Contraceptives for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/24—Drugs for disorders of the endocrine system of the sex hormones
Landscapes
- Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Endocrinology (AREA)
- Reproductive Health (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Organic Chemistry (AREA)
- Gynecology & Obstetrics (AREA)
- Pregnancy & Childbirth (AREA)
- Diabetes (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Steroid Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
A therapy method for treating infertility in a female host, comprising the administration of an ovarian follicular stimulating effective amount of exemestane, is provided.
Description
INFERTILITY TREATMENT WITH EXEMESTANE
Field of the invention The present invention relates to a method for treating infertility in a female host in need thereof comprising the administration of an ovarian follicular stimulating effective amount of exemestane to the female host.
Background of the invention io According to Harrison Dictionary, human infertility is defined as the inability to conceive after 12 months of unprotected sexual intercourse. There is a spectrum of infertility, ranging from reduced conception rates or the need of medical intervention to irreversible causes of infertility. Infertility can be attributed primarily to male factors in 25%, female factors in 5~%, and is unexplained in about 17% of couples.
is Ovulation is the process where an ovum or ova are released from the ovaries. The timing of ovulation within the menstrual cycle is of foremost importance for fertilization. It is well known that follicles acquire the ability to ovulate following growth and maturation stimulated by the pituitary gonadotropins. Ovulation induction is a therapeutic procedure commonly used to manage infertile patients. Ovulation induction is employed in 2o particular for the following two purposes: 1 ) to treat anovulation in patients with hypogonadotropic hypogonadism, polycystic ovary syndrome and other menstrual cycle disorders and 2) to stimulate multiple folliculogenesis in patients (mostly with normal menstrual cycles) who are candidates for assisted reproduction techniques.
These procedures are also termed controlled ovarian stimulation or hyperstimulation.
However 2s there are several complications caused by ovulation induction, including for instance multiple gestations and ovarian hyperstimulation syndrome. The complications mostly occur in polycystic ovary syndrome patients and/or full-dose gonadotropin regimens are employed.
Field of the invention The present invention relates to a method for treating infertility in a female host in need thereof comprising the administration of an ovarian follicular stimulating effective amount of exemestane to the female host.
Background of the invention io According to Harrison Dictionary, human infertility is defined as the inability to conceive after 12 months of unprotected sexual intercourse. There is a spectrum of infertility, ranging from reduced conception rates or the need of medical intervention to irreversible causes of infertility. Infertility can be attributed primarily to male factors in 25%, female factors in 5~%, and is unexplained in about 17% of couples.
is Ovulation is the process where an ovum or ova are released from the ovaries. The timing of ovulation within the menstrual cycle is of foremost importance for fertilization. It is well known that follicles acquire the ability to ovulate following growth and maturation stimulated by the pituitary gonadotropins. Ovulation induction is a therapeutic procedure commonly used to manage infertile patients. Ovulation induction is employed in 2o particular for the following two purposes: 1 ) to treat anovulation in patients with hypogonadotropic hypogonadism, polycystic ovary syndrome and other menstrual cycle disorders and 2) to stimulate multiple folliculogenesis in patients (mostly with normal menstrual cycles) who are candidates for assisted reproduction techniques.
These procedures are also termed controlled ovarian stimulation or hyperstimulation.
However 2s there are several complications caused by ovulation induction, including for instance multiple gestations and ovarian hyperstimulation syndrome. The complications mostly occur in polycystic ovary syndrome patients and/or full-dose gonadotropin regimens are employed.
The inventor of the present invention has found that exemestane can be safely used in ovarian follicular stimulation for treating infertility in a host in need thereof, namely without causing the above side effects.
Exemestane was first taught by US patent 4,808,616 and it is currently administered orally at the dosage of 25 mg/day in treating breast cancer in postmenopausal women.
Exemestane is endowed with a peculiar mechanism of aromatase inhibition. The aromatase enzyme (450aro,r,) is a specific form of cytochrome P450 hemoprotein composed of a P450 (heme) moiety and a peptidic moiety. The enzyme catalyzes a multistep reaction leading to aromatization of the A ring of the androgen substrate io (mainly androstenedione) to estrone, requiring the presence of the cofactor NADPH.
After this enzymatic reaction, the enzyme molecule is once more available to perform a new aromatization. The exemestane's mechanism of aromatase inhibition has been extensively studied and the compound has been found to cause enzyme inactivation. In fact exemestane, structurally related to the natural substrate androstenedione, is initially is recognized by the aromatase enzyme as a false substrate, therefore it competes with androstenedione at the active site of the enzyme. The compound is then transformed (through a NADPH-dependent mechanism) to an intermediate which binds irreversibly to the enzyme causing its inactivation (also known as suicide inhibition).
Therefore the enzyme is definitely inactivated and de novo enzyme synthesis is required for oestrogen 2o production.
The newly found therapeutic utility of exemestane is actually surprising. From the pharmacological point of view, the ovarian follicular stimulating activity of exemestane may be found in several concurrent factors, including its peculiar mechanism of aromatase inactivation, the dosage and the treatment schedule.
2s Description of the invention A first object of the present invention is to provide a method for treating infertility in a female host in need thereof comprising the administration of a therapeutically effective follicular stimulating amount of exemestane to said host.
Exemestane was first taught by US patent 4,808,616 and it is currently administered orally at the dosage of 25 mg/day in treating breast cancer in postmenopausal women.
Exemestane is endowed with a peculiar mechanism of aromatase inhibition. The aromatase enzyme (450aro,r,) is a specific form of cytochrome P450 hemoprotein composed of a P450 (heme) moiety and a peptidic moiety. The enzyme catalyzes a multistep reaction leading to aromatization of the A ring of the androgen substrate io (mainly androstenedione) to estrone, requiring the presence of the cofactor NADPH.
After this enzymatic reaction, the enzyme molecule is once more available to perform a new aromatization. The exemestane's mechanism of aromatase inhibition has been extensively studied and the compound has been found to cause enzyme inactivation. In fact exemestane, structurally related to the natural substrate androstenedione, is initially is recognized by the aromatase enzyme as a false substrate, therefore it competes with androstenedione at the active site of the enzyme. The compound is then transformed (through a NADPH-dependent mechanism) to an intermediate which binds irreversibly to the enzyme causing its inactivation (also known as suicide inhibition).
Therefore the enzyme is definitely inactivated and de novo enzyme synthesis is required for oestrogen 2o production.
The newly found therapeutic utility of exemestane is actually surprising. From the pharmacological point of view, the ovarian follicular stimulating activity of exemestane may be found in several concurrent factors, including its peculiar mechanism of aromatase inactivation, the dosage and the treatment schedule.
2s Description of the invention A first object of the present invention is to provide a method for treating infertility in a female host in need thereof comprising the administration of a therapeutically effective follicular stimulating amount of exemestane to said host.
According to a preferred embodiment of the invention, a method is provided for inducing ovarian follicular stimulation in a female host in need thereof comprising the administration and subsequent removal of a therapeutically effective follicular stimulating and/or inhibiting amount of exemestane to said host.
A female host, according to the invention, is for instance a mammalian female, in particular a woman. Preferred examples of such hosts are patients with hypogonadotropic hypogonadism, polycystic ovary syndrome and other menstrual cycle disorders, and patients who otherwise are candidate for assisted reproduction techniques.
to The clinical terms as used herein have their plain meanings, well known in the art.
In any case, anovulation refers to lack of ovulation, of course. Ovarian follicular stimulation refers to the process wherein exemestane is used to bring about ovulation in female hosts, who are otherwise anovulatory, resulting in induction of follicular rupture and ovulation of fertilizable oocytes.
is As used herein, the term "a therapeutically effective follicular stimulating amount" refers to an amount which is effective, upon single or multiple dose administration to the patient, in treating infertility e.g. by inducing ovarian follicular stimulation either when being taken or after its stoppage causing a rebound hyperstimulation of the ovaries.
According to a further preferred embodiment of the invention, a method is provided for 2o inducing ovarian follicular stimulation in a female host suffering from hypogonadotropic hypogonadism, polycystic ovary syndrome and other menstrual cycle disorders, or who is candidates for assisted reproduction techniques, comprising the administration of a therapeutically effective follicular stimulating amount of exemestane to said host.
A further object of the invention is the use of exemestane in the manufacture of a 2s medicament for use in treating infertility in a female host.
The invention also provides the use of exemestane in the manufacture of a medicament for use in inducing ovarian follicular stimulation in a female host.
A female host, according to the invention, is for instance a mammalian female, in particular a woman. Preferred examples of such hosts are patients with hypogonadotropic hypogonadism, polycystic ovary syndrome and other menstrual cycle disorders, and patients who otherwise are candidate for assisted reproduction techniques.
to The clinical terms as used herein have their plain meanings, well known in the art.
In any case, anovulation refers to lack of ovulation, of course. Ovarian follicular stimulation refers to the process wherein exemestane is used to bring about ovulation in female hosts, who are otherwise anovulatory, resulting in induction of follicular rupture and ovulation of fertilizable oocytes.
is As used herein, the term "a therapeutically effective follicular stimulating amount" refers to an amount which is effective, upon single or multiple dose administration to the patient, in treating infertility e.g. by inducing ovarian follicular stimulation either when being taken or after its stoppage causing a rebound hyperstimulation of the ovaries.
According to a further preferred embodiment of the invention, a method is provided for 2o inducing ovarian follicular stimulation in a female host suffering from hypogonadotropic hypogonadism, polycystic ovary syndrome and other menstrual cycle disorders, or who is candidates for assisted reproduction techniques, comprising the administration of a therapeutically effective follicular stimulating amount of exemestane to said host.
A further object of the invention is the use of exemestane in the manufacture of a 2s medicament for use in treating infertility in a female host.
The invention also provides the use of exemestane in the manufacture of a medicament for use in inducing ovarian follicular stimulation in a female host.
The effect of exemestane on ovarian follicular stimulation can for instance be seen in animal models once its administration is stopped with a resultant increase in follicle development and rupture.
In effecting treatment according to the invention, exemestane can be administered in any form or mode, which makes the compound bioavailable in therapeutically effective amounts. For example, routes of administration include oral, sublingual, intranasal, subcutaneous, intradermal, intraperitoneal, intramuscularly, intravenous, transdermal, vaginal, rectal and the like. Oral or intramuscular administration is generally preferred. One skilled in the art of preparing formulations can readily select the proper form and mode of administration depending upon the particular circumstances. For instance, examples of suitable oral forms are tablets, capsules, sugar and film coated tablets. The dosage of exemestane to be used is, of course, dependent on various factors such as the host to be treated (e.g. age, weight and general status of health), and the schedule of the treatment.
Exemestane can be administered to a woman, for instance orally, at a dosage range varying from about 5 mg/day to about 200 mg/day, possibly in divided doses, e.g. from 2 to 3 or 4.
According to a preferred schedule of treatment, exemestane is administered in the early part of the menstrual cycle (day 5 to day 7) and then stopped or it is administered throughout the entire cycle and then discontinued, in order to achieve the desired effective hematic follicular stimulating hormone level.
According to another aspect of the present invention, there is provided a use of exemestane for treating infertility in a female host.
According to yet another aspect of the present invention, 5 there is provided a pharmaceutical composition comprising a therapeutically effective follicular stimulating amount of exemestane and a pharmaceutically acceptable carrier or diluent, for treating infertility in a female host.
A further aspect of this invention is a commercial package comprising a composition of the invention, with instructions for its use in the treatment of any of the conditions described herein.
In effecting treatment according to the invention, exemestane can be administered in any form or mode, which makes the compound bioavailable in therapeutically effective amounts. For example, routes of administration include oral, sublingual, intranasal, subcutaneous, intradermal, intraperitoneal, intramuscularly, intravenous, transdermal, vaginal, rectal and the like. Oral or intramuscular administration is generally preferred. One skilled in the art of preparing formulations can readily select the proper form and mode of administration depending upon the particular circumstances. For instance, examples of suitable oral forms are tablets, capsules, sugar and film coated tablets. The dosage of exemestane to be used is, of course, dependent on various factors such as the host to be treated (e.g. age, weight and general status of health), and the schedule of the treatment.
Exemestane can be administered to a woman, for instance orally, at a dosage range varying from about 5 mg/day to about 200 mg/day, possibly in divided doses, e.g. from 2 to 3 or 4.
According to a preferred schedule of treatment, exemestane is administered in the early part of the menstrual cycle (day 5 to day 7) and then stopped or it is administered throughout the entire cycle and then discontinued, in order to achieve the desired effective hematic follicular stimulating hormone level.
According to another aspect of the present invention, there is provided a use of exemestane for treating infertility in a female host.
According to yet another aspect of the present invention, 5 there is provided a pharmaceutical composition comprising a therapeutically effective follicular stimulating amount of exemestane and a pharmaceutically acceptable carrier or diluent, for treating infertility in a female host.
A further aspect of this invention is a commercial package comprising a composition of the invention, with instructions for its use in the treatment of any of the conditions described herein.
Claims (24)
1. ~A pharmaceutical composition comprising a therapeutically effective follicular stimulating amount of exemestane and a pharmaceutically acceptable carrier or diluent, for treating infertility in a female host.
2. ~A pharmaceutical composition comprising a therapeutically effective follicular stimulating amount of exemestane and a pharmaceutically acceptable carrier or diluent, for inducing ovarian follicular stimulation in a female host.
3. ~The composition as claimed in claim 1 or 2, wherein the female host is a mammalian female.
4. ~The composition as claimed in claim 1 or 2, wherein the female host is a woman.
5. ~The composition as claimed in claim 1 or 2, wherein the female host is suffering from hypogonadotropic hypogonadism.
6. ~The composition as claimed in claim 1 or 2, wherein the female host is suffering from polycystic ovary syndrome.
7. ~The composition as claimed in claim 1 or 2, wherein the female host is a candidate for assisted reproduction technique.
8. ~The composition as claimed in any one of claims 1 to 7 which is in a dosage form of about 5 mg/day to about 200 mg/day.
9. ~Use of exemestane in the manufacture of a medicament for use in treating infertility in a female host.
10. Use of exemestane in the manufacture of a medicament for use in inducing ovarian follicular stimulation in a female host.
11. The use as claimed in claim 9 or 10, wherein the female host is a mammalian female.
12. The use as claimed in claim 9 or 10, wherein the female host is a woman.
13. The use as claimed in claim 9 or 10, wherein the female host is suffering from hypogonadotropic hypogonadism.
14. The use as claimed in claim 9 or 10, wherein the female host is suffering from polycystic ovary syndrome.
15. The use as claimed in claim 9 or 10, wherein the female host is a candidate for assisted reproduction technique.
16. Use of exemestane for treating infertility in a female host.
17. Use of exemestane for inducing ovarian follicular stimulation in a female host.
18. The use as claimed in claim 16 or 17, wherein the female host is a mammalian female.
19. The use as claimed in claim 16 or 17, wherein the female host is a woman.
20. The use as claimed in claim 16 or 17, wherein the female host is suffering from hypogonadotropic hypogonadism.
21. The use as claimed in claim 16 or 17, wherein the female host is suffering from polycystic ovary syndrome.
22. The use as claimed in claim 16 or 17, wherein the female host is a candidate for assisted reproduction technique.
23. A commercial package comprising: (i) a container containing therein the pharmaceutical composition as claimed in any one of claims 1 to 8, and (ii) a written matter describing an indication for the use thereof for treating infertility in a female host.
24. A commercial package comprising: (i) a container containing therein the pharmaceutical composition as claimed in any one of claims 2 to 8, and (ii) a written matter describing an indication for the use thereof for inducing ovarian follicular stimulation in a female host.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US39332002P | 2002-07-02 | 2002-07-02 | |
| US60/393,320 | 2002-07-02 | ||
| PCT/US2003/016252 WO2004004634A2 (en) | 2002-07-02 | 2003-07-02 | Infertility treatment with exemestane |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2491372A1 true CA2491372A1 (en) | 2004-01-15 |
Family
ID=30115565
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002491372A Abandoned CA2491372A1 (en) | 2002-07-02 | 2003-07-02 | Infertility treatment with exemestane |
Country Status (12)
| Country | Link |
|---|---|
| EP (1) | EP1531829A2 (en) |
| JP (1) | JP2005536490A (en) |
| KR (1) | KR20050077045A (en) |
| CN (1) | CN1665516A (en) |
| AU (1) | AU2003247404A1 (en) |
| BR (1) | BR0312393A (en) |
| CA (1) | CA2491372A1 (en) |
| IL (1) | IL165813A0 (en) |
| MX (1) | MXPA05000251A (en) |
| PL (1) | PL373219A1 (en) |
| WO (1) | WO2004004634A2 (en) |
| ZA (1) | ZA200410135B (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR102432156B1 (en) * | 2020-05-18 | 2022-08-11 | 제주대학교 산학협력단 | Composition comprising chemical material for inhibiting gonadal maturation in fishes and method for inhibiting gonadal maturation in fishes using the same |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| HUP0303795A2 (en) * | 2001-04-17 | 2004-03-29 | Ares Trading S.A. | Use of aromatase inhibitors for preparation of pharmaceutical composition suitable to enhance assisted reproduction |
| PL366744A1 (en) * | 2001-04-17 | 2005-02-07 | Ares Trading S.A. | Single dose aromatase inhibitor for treating infertility |
-
2003
- 2003-07-02 BR BR0312393-6A patent/BR0312393A/en not_active IP Right Cessation
- 2003-07-02 PL PL03373219A patent/PL373219A1/en not_active Application Discontinuation
- 2003-07-02 WO PCT/US2003/016252 patent/WO2004004634A2/en active Application Filing
- 2003-07-02 CA CA002491372A patent/CA2491372A1/en not_active Abandoned
- 2003-07-02 CN CN038157306A patent/CN1665516A/en active Pending
- 2003-07-02 AU AU2003247404A patent/AU2003247404A1/en not_active Abandoned
- 2003-07-02 MX MXPA05000251A patent/MXPA05000251A/en unknown
- 2003-07-02 EP EP03762980A patent/EP1531829A2/en not_active Withdrawn
- 2003-07-02 JP JP2004519563A patent/JP2005536490A/en active Pending
- 2003-07-02 KR KR1020057000051A patent/KR20050077045A/en not_active Ceased
-
2004
- 2004-12-16 IL IL16581304A patent/IL165813A0/en unknown
-
2005
- 2005-12-15 ZA ZA200410135A patent/ZA200410135B/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| CN1665516A (en) | 2005-09-07 |
| EP1531829A2 (en) | 2005-05-25 |
| WO2004004634A2 (en) | 2004-01-15 |
| ZA200410135B (en) | 2006-07-26 |
| BR0312393A (en) | 2005-04-12 |
| MXPA05000251A (en) | 2005-07-15 |
| PL373219A1 (en) | 2005-08-22 |
| IL165813A0 (en) | 2006-01-15 |
| KR20050077045A (en) | 2005-07-29 |
| JP2005536490A (en) | 2005-12-02 |
| WO2004004634A3 (en) | 2004-04-08 |
| AU2003247404A1 (en) | 2004-01-23 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Mitwally et al. | Aromatase inhibition: a novel method of ovulation induction in women with polycystic ovary syndrome | |
| AU743277B2 (en) | Preparations for the treatment of metabolic syndrome containing human growth hormone in combination with a cortisol synthesis inhibitor | |
| ZA200600201B (en) | Methods of hormonal treatment utilizing contraceptive regimens with continuous estrogen administration | |
| EP1854465A1 (en) | Use of 4,17 beta-dihydroxyandrost-4-ene-3-one for treating cancers | |
| Lin et al. | Clinical application of dehydroepiandrosterone in reproduction: A review of the evidence | |
| EA003371B1 (en) | Use of biogenic estrogen sulfamates for hormone replacement therapy | |
| KR19990082080A (en) | Pharmaceutical formulations comprising LHRH-like substances and antiestrogens for treating gynecological diseases | |
| NZ521315A (en) | Exemestane for first-line treatment of breast cancer | |
| CA2491372A1 (en) | Infertility treatment with exemestane | |
| EP1383578B1 (en) | Single dose aromatase inhibitor for treating infertility | |
| HK1077736A (en) | Infertility treatment with exemestane | |
| UA51627C2 (en) | Restoration of tonic estrogen secretion by ovaries for long-term treatment regimens | |
| NZ538347A (en) | Use of antiprogestins for the induction of apoptosis in a cell | |
| US11376263B2 (en) | Cyproterone acetate compositions and uses thereof | |
| Purohit et al. | Inhibition of steroid sulphatase activity via the percutaneous route: a new option for breast cancer therapy | |
| US20030158168A1 (en) | Composition for combined use of aromatase inhibitors | |
| Ziporyn | LHRH: clinical applications growing | |
| Bulun et al. | Medical therapies: aromatase inhibitors | |
| US20100087407A1 (en) | use of aromatase inhibitors | |
| Sterrenburg et al. | Drugs in reproductive medicine | |
| Shrivastav | Aromatase Inhibitors—Their Role in the Treatment of Infertility | |
| Seal | The practical management of | |
| RU2275923C1 (en) | Preparation for regulating menstrual cycle in case of secondary normogonadotropic amenorrhea and oligomenorrhea and method for therapy | |
| RU2289409C1 (en) | Method for rehabilitation of women after medicinal artificial abortion | |
| Gordon et al. | Management of pituitary gonadal function via gonadotrophin releasing hormone (GnRH) antagonists, including ovulation induction by co-administration of either gonadotrophins or pulsatile GnRH |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| FZDE | Discontinued |