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Title: Method for the
therapeutic management of extrauterine proliferation of endometrial
tissue, chronic pelvic pain and fallopian tube obstruction
United States Patent: 7,005,418
Issued: February
28, 2006
Inventors: Riethmuller-Winzen; Hilde
(Frankfurt, DE); Engel; Jurgen (Alzenau, DE); Felberbaum; Ricardo (Lubeck,
DE); Diedrich; Klaus (Gross-Sarau, DE); Küpker; Wolfgang (Lubeck, DE)
Assignee: Zentaris GmbH (Frankfurt am
Main, DE)
Appl. No.: 666146
Filed: September 20, 2000
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Web Seminars -- Pharm/Biotech/etc.
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Abstract
The present inventions provides a method
for therapeutic management of extrauterine proliferation of endometrial
tissue, chronic pelvic pain and fallopian tube obstruction by short term
induction treatment with an LH-RH antagonist for 4 to 12 weeks. According
to another aspect of the present invention, the short term LH-RH treatment
is followed by the combined or separate administration of one or more
active agents selected from the group consisting of a contraceptive,
preferably an oral contraceptive, a non-steroidal anti-rheumatic agent, an
analgetic, an androgen other than a 17-alpha-alkyl substituted
testosterone or any combinations thereof. According to a further aspect of
the present invention a pharmaceutical composition comprising an LHRH
antagonist and one ore more active agents selected from the group
consisting of a contraceptive, preferably an oral contraceptive, a
non-steroidal anti-rheumatic agent, an analgetic, an androgen other than a
17-alpha-alkyl substituted testosterone or any combinations thereof are
provided.
SUMMARY OF THE INVENTION
In the treatment of extrauterine endometrial tissue with an LHRH
antagonist, therapy is started on menstrual cycle day one to three. Before
starting LHRH-antagonist therapy the diagnosis is performed by
laparoscopy. In cases of severe pain, LHRH antagonist therapy might be
initiated without prior laparascopy.
Therapy will continue until clinical symptomatology has resolved and no
proliferation of the endometrium is seen. Due to the immediate onset of
suppression of the gonadotropins LH and FSH as well of sex steroids
estradiol and progesterone no further proliferation of the endometrium
occurs. Benign tumors or other sex steroid dependent lesions, like
endometriosis decrease within four to twelve weeks of therapy. Due to the
lack of flare-up no ovarian cysts develop.
Furthermore, no hormonal withdrawal symptoms are seen as the estradiol
values are kept in the range of the early follicular phase of 35 to 80
pg/ml, preferably between about 45-75 pg/ml, more preferably between about
50-75 pg/ml without further increase or decrease. No titering of the
dosage of the LHRH antagonist, e.g. by conducting a costly progesterone
challenge test, is necessary.
The method of therapeutic management of extrauterine proliferation of
endometrial tissue the improvement according to the invention therefore
embraces:
immediate reduction of ectopic
endometrial tissue
prevention of any progress of the
disease
avoidance of hormonal withdrawal
symptoms
prevention of ovarian cyst formation,
demineralization of bones as well as of gastrointestinal or hepatic
disorders
start of medical therapy on cycle day one to three and maintenance of
estradiol levels at values of the early follicular phase throughout the
entire duration of treatment by means of administration of a LHRH
antagonist wherein the antagonist is preferabely cetrorelix, teverelix,
ganirelix, antide or abarelix. The antagonist can also be the LHRH
antagonist D-63153
(Ac-D-Nal-D-pCl-Phe-D-Pal-Ser-N-Me-Tyr-D-Hci-Nle-Arg-Pro-D-Ala-NH2) as
described in the German Patent Application No. 199 11 771.3 filed on Mar.
11, 1999.
The LHRH antagonist may be given for 4 to 12 weeks in a weekly dose of 3
to 10 mg per week or for 4 to 12 weeks in a daily dose of 0.25 mg to 0.5
mg/day.
It is also possible to give the LHRH antagonist 4 to 12 weeks in a monthly
dose of 12 to 40 mg per month.
In a repeat therapeutic treatment the LHRH antagonist is given for 4 to 12
weeks and the treatment is repeated two or three times a year, whereby a
repeated treatment does not following directly after a short-term
induction treatment. Usually a period of time of weeks or months, where no
LHRH antagonist is administered, is between the end of the short-term
induction treatment and the start of the repeat treatment.
To demonstrate the feasibility to maintain a low estradiol secretion under
adjusted LHRH-antagonist treatment so that a therapeutic suppression
occurs without withdrawal symtoms nine patients with confirmed
endometriosis were treated with 3 mg of Cetrorelix acetate s.c. by weekly
administration for 8 weeks. While patients compliance was excellent
avoiding any hot flushes or other withdrawal symptoms and without any
progress of the disease confimed by 2nd look laparascopy the
mean estradiol serum concentrations oscillated between 37 pg/ml and 64
pg/ml, preferably between 45-75 pg/ml, more preferably between about 50-75
pg/ml. Histological biopsies showed no proliferation of the endometrium at
the end of treatment. No ovarian cyst formation occurred.
The FIG. 1 (see Original Patent) shows the continuous estradiol suppression to values of the
early follicular phase (range of 35 pg/ml to 80 pg/ml, preferably between
45-75 pg/ml more preferably between about 50-75 pg/ml) obtained in
patients with endometriosis by a weekly dose of 3 mg of Cetrorelix (LHRH
antagonist) for 8 weeks. Immediate and continuous suppression of estradiol
levels is obtained without any signs of estradiol withdrawal symptoms and
without proliferation of the endometrium at the end of treatment.
FIG. 2 (see Original Patent) shows estradiol serum levels after administration of cetrorelix at
a weekly dose of 1 mg resp. 3 mg once per week. The estradiol serum levels
are between about 35-80 pg/ml, preferably between about 45-75 pg/ml, more
preferably between about 50-75 pg/ml.
The endometriosis patient with distinctive symptomatic pain is suffering
from a chronic disease. Surgical methods in sense of curative therapy as
well as medicinal treatment to suppress the sexual steroid secretion of
the patient often result only in a temporary improvement. The relapse rate
of the discomforts is very high and about 70% within 5 years after
finishing therapy (Schweppe, 1999).
At the same time the radical surgical therapy and the suppression of the
estrogen secretion leads to considerable side effects. The radical
surgical therapy in sense of hysterectomy with bilateral adnexectomy is no
adequate therapy for the younger, premenopausal woman. The chronical lack
of estrogen leads to the following vegetative symptoms: hot flashes,
sweating, dryness of the vagina, depressive feelings and also holds the
risk of osteoporosis. The alternative therapy with the synthetic steroidal
compound Danazol may cause virilizing symptoms because of the androgenic
effect.
Aim of the medicinal therapy of patients with endometriosis with
symptomatic pain is to obtain a treatment without side effects, especially
avoiding the negative effects of estrogen suppression and which is
long-lasting after finishing therapy. The specific pharmacological mode of
action of LHRH antagonists allows new possibilities for treatment of
endometriosis.
The weekly administration of an adequate dose of an LHRH antagonist, e.g.
3 mg Cetrotide® s.c./ per week over a period of eight weeks leads to a
controlled suppression of estrogen secretion so that serum concentrations
between about 35 pg/ml and about 80 pg/ml, preferably between about 45-75
pg/ml, more preferably between about 50-75 pg/ml are obtained. In this
serum concentration range no vegetative symptoms arise. Also the
development of osteoporosis can be avoided. The symptomatic pain will be
effectively suppressed in all stages of the disease (rAFS I-IV). In the
stages rAFS I-II a clinical regression of the disease in sense of decrease
of the implantation area is noticed (Felberbaum et. al., 2000).
In a preferred embodiment of this invention, after this treatment period
of eight to twelve weeks the patient could take a contraceptive,
preferably an oral contraceptive, preferably with gestagen components,
unless there is a wish for pregnancy. In this connection combinations with
Lynestronol 2 mg with 0.04 mg Ethinylestradiol or 2.5 mg Lynestrenol with
0.05 mg of Ethinylestradiol (e.g. Yermonil®, Lyn-ratiopharm-Sequenz®) have
to be mentioned.
A combination therapy with androgens other than 17-alpha-alkyl substituted
testosterones such as danazol may also be applied subsequently to the
short-term induction regimen with the LHRH antagonist either alone or in
combination with non-steroidal anti-rheumatics and/or analgetics. An
example for a suitable androgene is halotestin™ (fluoximesterone).
The treatment with a contraceptive, preferably an oral contraceptive,
preferably containing gestagens, should be individually continued until
typical pain sensation occurs. In this stage the patient will have
relatively small menstrual bleeding as an effect of the gestagen component
of this contraceptive, preferably oral contraceptive. For covering also
the especially critical pre-menstrual and menstrual days with regard to
pain sensation in this phase a concomitant medication with appropriate
non-steroidal anti-rheumatic drugs, e.g. diclophenac, ibuprofen,
indometeacin, oxicam derivates or acetylsalicylic acid may be given. Also
an analgetic such as flupirtinmaleat (Katadolon®) can be administered.
If further pain symptoms occur during this combination therapy with
gestagenic contraceptives, preferably oral contraceptives, a daily, weekly
or monthly therapy with the adequate dose of an LHRH antagonist as
described above may be repeated. Detailed information on the respective
treatment options are given below. If the patient is absolutely free of
pain treatment can be changed to gestagenic contraceptive, preferably oral
contraceptives, in combination with concomitant medication of appropriate
non-steroid anti-rheumatic drugs or analgetics.
This therapy using the intermittent administration of an LHRH antagonist
leads to a new and innovative unlimited treatment without side effects and
lowers treatment burden for the patient significantly.
PHARMACEUTICAL FORMULATIONS SUITABLE FOR TREATMENT
Pharmaceutical formulations of the LHRH antagonist suitable for the
therapeutic management of extrauterine proliferation of endometrial
tissue, chronic pelvic pain and fallopian tube obstruction may be for
example
a) acetate salt formulations in the
concentration of 1 mg/1 ml or lower where the powder may be dissolved in
Water for Injection (WfI) or in Gluconic Acid (GA);
b) acetate salt formulations in the
concentration of 1.5 mg/1 ml to 5.0 mg/1 ml, preferably 2.5 mg/1 ml where
the powder may be dissolved in Water for Injection (WfI) or in Gluconic
Acid (GA);
c) pamoate salt formulations in the
concentration of 10 mg/1 ml to 30 mg/l ml, preferably 15 mg/1 ml where the
lyophylisate powder may be dissolved in Gluconic Acid (GA) or in Water for
Injection (WfI.
According to one aspect of the present invention in the method of
therapeutic management of extrauterine proliferation of endometrial
tissue, chronic pelvic pain and/or fallopian tube obstruction (FTO), the
improvement consisting of administration of an LHRH antagonist in the form
of a short-term induction treatment for a period of about 4 to 12 weeks to
a patient in need of such treatment, whereby subsequently the
administration of the LHRH antagonist is ceased, is provided.
The duration of the short term induction treatment is about 4 to about 12
weeks, that means that the treatment can be between about 28 to about 84
days or from about one to about three months.
According to another aspect of the present invention in a method as
mentioned above the improvement is provided, wherein the LHRH antagonist
is administered such that the estrogen serum concentration level is
between about 35 pg/ml and about 80 pg/ml, preferably between about 45-75
pg/ml, more preferably about 50-75 pg/ml.
According to another aspect of the present invention in a method as
mentioned above the improvement is provided, characterized in that the
short-term induction treatment with the LHRH antagonist is followed by
administration of a contraceptive, preferably an oral contraceptive.
According to another aspect of the present invention in a method as
mentioned above the improvement is provided, characterized in that the
short-term induction treatment with the LHRH antagonist is followed by
administration of a non-steroidal anti-rheumatic agent.
According to another aspect of the present invention in a method as
mentioned is above the improvement is provided, characterized in that the
short-term induction treatment with the LHRH antagonist is followed by
administration of an analgetic.
According to another aspect of the present invention in a method as
mentioned above the improvement is provided, characterized in that the
short-term induction treatment with the LHRH antagonist is followed by
administration of an androgen other than a 17-alpha-alkyl substituted
testosterone.
According to another aspect of the present invention in a method as
mentioned above the improvement is provided, characterized in that the
short-term induction treatment with the LHRH antagonist is followed by the
combined or separate administration of one or more active agents selected
from the group consisting of a contraceptive, preferably an oral
contraceptive, a non-steroidal anti-rheumatic agent, an analgetic, an
androgen other than a 17-alpha-alkyl substituted testosterone or any
combinations thereof.
According to another aspect of the present invention in a method as
mentioned above the improvement is provided, characterized in that the
LHRH antagonist is administered starting in the early to mid follicular
phase, preferably on cycle day one to three.
According to another aspect of the present invention in a method as
mentioned above the improvement is provided, characterized in that the
LHRH antagonist is selected from the group consisting of cetrorelix,
teverelix, ganirelix, antide, abarelix and D-63153.
According to another aspect of the present invention in a method as
mentioned above the improvement is provided, characterized in that the
LHRH antagonist is administered during the short-term induction treatment
for 4 to 12 weeks at a weekly dose of 3 to 10 mg per week.
According to another aspect of the present invention in a method as
mentioned above the improvement is provided, characterized in that the
LHRH antagonist is administered during the short-term induction treatment
for 4 to 12 weeks at a daily dose of 0.25 mg to 0.5 mg/day.
According to another aspect of the present invention in a method as
mentioned above the improvement is provided, characterized in that the
LHRH antagonist is administered during the short-term induction treatment
for 4 to 12 weeks at a monthly dose of 12 to 40 mg per month.
According to another aspect of the present invention in a method as
mentioned above the improvement is provided, characterized in that the
LHRH antagonist is given for the induction treatment during 4 to 12 weeks
and the treatment is repeated two or three times a year.
According to a further aspect of the present invention a pharmaceutical
composition for treating extrauterine proliferation of endometrial tissue,
chronic pelvic pain and/or fallopian tube obstruction (FTO) comprising an
LHRH antagonist and optionally one or more agents selected from the group
consisting of a contraceptive, preferably an oral contraceptive, a
non-steroidal anti-rheumatic agent, an analgetic agent, an androgen agent
other than a 17-alpha-alkyl substituted testosterone or any combinations
thereof, optionally together with pharmaceutically acceptable excipients,
whereby the LH-RH antagonist is administered to a patient in need thereof
in a short term induction treatment for a period of about 4 to 12 weeks,
then the administration of the LH-RH antagonist is ceased and optionally
the one or more agents selected from the group consisting of a
contraceptive, preferably an oral contraceptive, a non-steroidal
anti-rheumatic agent, an analgetic, an androgen other than a
17-alpha-alkyl substituted testosterone or any combinations thereof, are
administered together or separately to the patient is provided.
Suitable excipients and dosage forms are for example described by K. H.
Bauer, K. H. Frömming and C. Führer, Lehrbuch der Pharmazeutischen
Technologie, 6th edition, Stuttgart 1999, pages 163-186 (excipients)
and pages 227-386 (dosage forms), including the references as cited
therein.
The LH-RH antagonist can be administered for example sucutaneous (s.c.),
intramuscular (i.m.) or inhalative. The agents selected from the group
consisting of a contraceptive, preferably an oral contraceptive, a
non-steroidal anti-rheumatic agent, an analgetic, an androgen other than a
17-alpha-alkyl substituted testosterone or any combinations thereof can be
administered as known in the art (see for example the German, European or
U.S. pharmacopoeia), preferably oral or inhalative.
According to another aspect of the present invention, a pharmaceutical
composition as mentioned above is provided wherein the LHRH antagonist is
administered such that the estrogen serum concentration level is between
about 35 pg/ml and about 80 pg/ml, preferably between about 45-75 pg/ml,
more preferably about 50-75 pg/ml.
According to another aspect of the present invention, a pharmaceutical
composition as mentioned above is provided wherein the short-term
induction treatment with the LHRH antagonist is followed by administration
of a contraceptive, preferably an oral contraceptive.
According to another aspect of the present invention, a pharmaceutical
composition as mentioned above is provided wherein the short-term
induction treatment with the LHRH antagonist is followed by administration
of a non-steroidal anti-rheumatic agent.
According to another aspect of the present invention, a pharmaceutical
composition as mentioned above is provided wherein the short-term
induction treatment with the LHRH antagonist is followed by administration
of an analgetic.
According to another aspect of the present invention, a pharmaceutical
composition as mentioned above is provided wherein the short-term
induction treatment with the LHRH antagonist is followed by administration
of an androgen other than a 17-alpha-alkyl substituted testosterone.
According to another aspect of the present invention, a pharmaceutical
composition as mentioned above is provided wherein the short-term
induction treatment with the LHRH antagonist is followed by the combined
or separate administration of one or more active agents selected from the
group consisting of a contraceptive, preferably an oral contraceptive, a
non-steroidal anti-rheumatic agent, an analgetic, an androgen other than a
17-alpha-alkyl substituted testosterone or any combinations thereof.
According to another aspect of the present invention, a pharmaceutical
composition as mentioned above is provided wherein the LHRH antagonist is
administered starting in the early to mid follicular phase, preferably on
cycle day one to three.
According to another aspect of the present invention, a pharmaceutical
composition as mentioned above is provided wherein the LHRH antagonist is
selected from the group consisting of cetrorelix, teverelix, ganirelix,
antide, abarelix and D-63153.
According to another aspect of the present invention, a pharmaceutical
composition as mentioned above is provided wherein the LHRH antagonist is
administered during the short-term induction treatment for 4 to 12 weeks
at a weekly dose of 3 to 10 mg per week.
According to another aspect of the present invention, a pharmaceutical
composition as mentioned above is provided wherein the LHRH antagonist is
administered during the short-term induction treatment for 4 to 12 weeks
at a daily dose of 0.25 mg to 0.5 mg/day.
According to another aspect of the present invention, a pharmaceutical
composition as mentioned above is provided wherein the LHRH antagonist is
administered during the short-term induction treatment for 4 to 12 weeks
at a monthly dose of 12 to 40 mg per month.
According to another aspect of the present invention, a pharmaceutical
composition as mentioned above is provided wherein the LHRH antagonist is
given for the induction treatment during 4 to 12 weeks and the treatment
is repeated two or three times a year.
According to another aspect of the present invention, a pharmaceutical
composition as mentioned above is provided, wherein the the one or more
active agents selected from the group consisting of a contraceptive,
preferably an oral contraceptive, a non-steroidal anti-rheumatic agent, an
analgetic, an androgen other than a 17-alpha-alkyl substituted
testosterone or any combinations thereof, are in the same or separate
dosage forms.
According to another aspect of the present invention, a use of an LH-RH
antagonist for the preparation of a medicament for the therapeutic
management of extrauterine proliferation of endometrial tissue, chronic
pelvic pain and/or fallopian tube obstruction (FTO), whereby the LHRH
antagonist is administered in the form of a short-term induction treatment
for a period of about 4 to 12 weeks to a patient in need of such treatment
and then the administration of the LHRH antagonist is ceased, is provided.
According to another aspect of the present invention, a use of an LH-RH
antagonist as mentioned above is provided wherein the LHRH antagonist is
administered such that the estrogen serum concentration level is between
about 35 pg/ml and about 80 pg/ml, preferably between about 45-75 pg/ml,
more preferably about 50-75 pg/ml.
According to another aspect of the present invention, a use of an LH-RH
antagonist as mentioned above is provided, wherein the short-term
induction treatment with the LHRH antagonist is followed by administration
of a contraceptive, preferably an oral contraceptive.
According to another aspect of the present invention, a use of an LH-RH
antagonist as mentioned above is provided, wherein the short-term
induction treatment with the LHRH antagonist is followed by administration
of a non-steroidal anti-rheumatic agent.
According to another aspect of the present invention, a use of an LH-RH
antagonist as mentioned above is provided, wherein the short-term
induction treatment with the LHRH antagonist is followed by administration
of an analgetic.
According to another aspect of the present invention, a use of an LH-RH
antagonist as mentioned above is provided, wherein the short-term
induction treatment with the LHRH antagonist is followed by administration
of an androgen other than a 17-alpha-alkyl substituted testosterone.
According to another aspect of the present invention, a use of an LH-RH
antagonist as mentioned above is provided, wherein the short-term
induction treatment with the LHRH antagonist is followed by the combined
or separate administration of one or more active agents selected from the
group consisting of a contraceptive, preferably an oral contraceptive, a
non-steroidal anti-rheumatic agent, an analgetic, an androgen other than a
17-alpha-alkyl substituted testosterone or any combinations thereof.
According to another aspect of the present invention, a use of an LH-RH
antagonist as mentioned above is provided, wherein the LHRH antagonist is
administered starting in the early to mid follicular phase, preferably on
cycle day one to three.
According to another aspect of the present invention, a use of an LH-RH
antagonist as mentioned above is provided, wherein the LHRH antagonist is
selected from the group consisting of cetrorelix, teverelix, ganirelix,
antide, abarelix and D-63153.
According to another aspect of the present invention, a use of an LH-RH
antagonist as mentioned above is provided, wherein the LHRH antagonist is
administered during the short-term induction treatment for 4 to 12 weeks
at a weekly dose of 3 to 10 mg per week.
According to another aspect of the present invention, a use of an LH-RH
antagonist is as mentioned above is provided, wherein the LHRH antagonist
is administered during the short-term induction treatment for 4 to 12
weeks at a daily dose of 0.25 mg to 0.5 mg/day.
According to another aspect of the present invention, a use of an LH-RH
antagonist as mentioned above is provided, wherein the LHRH antagonist is
administered during the snort-term induction treatment for 4 to 12 weeks
at a monthly dose of 12 to 40 mg per month.
According to another aspect of the present invention, a use of an LH-RH
antagonist as mentioned above is provided, wherein the LHRH antagonist is
given for the induction treatment during 4 to 12 weeks and the treatment
is repeated two or three times a year.
According to another aspect of the present invention, a use of an LH-RH
antagonist and one or more active agents selected from the group
consisting of a contraceptive, preferably an oral contraceptive, a
non-steroidal anti-rheumatic agent, an analgetic, an androgen other than a
17-alpha-alkyl substituted testosterone, or any combinations thereof, for
the preparation of a medicament for the therapeutic management of
extrauterine proliferation of endometrial tissue, chronic pelvic pain
and/or fallopian tube obstruction (FTO), whereby the LHRH antagonist is
administered in the form of a short-term induction treatment for a period
of about 4 to 12 weeks to a patient in need of such treatment, then the
administration of the LHRH antagonist is ceased and the one or more active
agent selected from the group consisting of a contraceptive, preferably an
oral contraceptive, a non-steroidal anti-rheumatic agent, an analgetic, an
androgen other than a 17-alpha-alkyl substituted testosterone, or any
combinations thereof, are administered together or separately to the
patient, is provided.
According to another aspect of the present invention the use of an LH-RH
antagonist and one or more active agents as mentioned above is provided,
wherein the LHRH antagonist is administered such that the estrogen serum
concentration level is between about 35 pg/ml and about 80 pg/ml,
preferably between about 45-75 pg/ml, more preferably about 50-75 pg/ml.
According to another aspect of the present invention the use of an LH-RH
antagonist and one or more active agents as mentioned above is provided,
wherein the short-term induction treatment with the LHRH antagonist is
followed by administration of a contraceptive, preferably an oral
contraceptive.
According to another aspect of the present invention the use of an LH-RH
antagonist and one or more active agents as mentioned above is provided,
wherein the short-term induction treatment with the LHRH antagonist is
followed by administration of a non-steroidal anti-rheumatic agent.
According to another aspect of the present invention the use of an LH-RH
antagonist and one or more active agents as mentioned above is provided,
wherein the short-term induction treatment with the LHRH antagonist is
followed by administration of an analgetic.
According to another aspect of the present invention the use of an LH-RH
antagonist and one or more active agents as mentioned above is provided,
wherein the short-term induction treatment with the LHRH antagonist is
followed by administration of an androgen other than a 17-alpha-alkyl
substituted testosterone.
According to another aspect of the present invention the use of an LH-RH
antagonist and one or more active agents as mentioned above is provided,
wherein the short-term induction treatment with the LHRH antagonist is
followed by the combined or separate administration of one or more active
agents selected from the group consisting of a contraceptive, preferably
an oral contraceptive, a non-steroidal anti-rheumatic agent, an analgetic,
an androgen other than a 17-alpha-alkyl substituted testosterone or any
combinations thereof.
According to another aspect of the present invention the use of an LH-RH
antagonist and one or more active agents as mentioned above is provided,
wherein the LHRH antagonist is administered starting in the early to mid
follicular phase, preferably on cycle day one to three.
According to another aspect of the present invention the use of an LH-RH
antagonist and one or more active agents as mentioned above is provided,
wherein the LHRH antagonist is selected from the group consisting of
cetrorelix, teverelix, ganirelix, antide, abarelix and D-63153.
According to another aspect of the present invention the use of an LH-RH
antagonist and one or more active agents as mentioned above is provided,
wherein the LHRH antagonist is administered during the short-term
induction treatment for 4 to 12 weeks at a weekly dose of 3 to 10 mg per
week.
According to another aspect of the present invention the use of an LH-RH
antagonist and one or more active agents as mentioned above is provided,
wherein the LHRH antagonist is administered during the short-term
induction treatment for 4 to 12 weeks at a daily dose of 0.25 mg to 0.5
mg/day.
According to another aspect of the present invention the use of an LH-RH
antagonist and one or more active agents as mentioned above is provided,
wherein the LHRH antagonist is administered during the short-term
induction treatment for 4 to 12 weeks at a monthly dose of 12 to 40 mg per
month.
According to another aspect of the present invention the use of an LH-RH
antagonist and one or more active agents as mentioned above is provided,
wherein the LHRH antagonist is given for the induction treatment during 4
to 12 weeks and the treatment is repeated two or three times a year.
Claim 1 of 17 Claims
1. In the method of
therapeutic management of extrauterine proliferation of endometrial tissue,
chronic pelvic pain and/or fallopian tube obstruction, the improvement
consisting of administration of an LHRH antagonist in the form of a short
term induction treatment for a period of about 4 to 12 weeks to a patient in
need of such treatment, whereby subsequently the administration of the LHRH
antagonist is ceased.
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