Fibroid treatment
Michael O'Dell
Can anyone advise me on a treatment for uterine fibroids called 'RH Gn
Agonist', something that has been offered to my mother. References or net
sites or any info would be grately appreciated.
Mike
Michael O'Dell
Can anyone supply me with information on a treatment for uterine fibroids
called 'RH Gn Agonist'. References or web sites would be greatly
appreciated.
Thanks, Mike.
Eric Huang
Hi Mike,
Uterine fibroid, also known as uterinine leiomyoma, is the most common
uterine tumor. No need to worry because it is a benign tumor, but the
growths can become very large and cause pain by putting pressure on
nerves and other structures. The tumors can also cause vaginal
bleeding. The usual treatment for fibroids is complete hysterectomy.
Fibroids are also estrogen-sensitive -- they grow much larger during
pregnancy, when they are commonly detectect, and decrease in size
following menopause. Therefor, if the patient decides against
surgery, the fibroid can be treated with various anti-hormone
therapies.
One choice would be to directly block estrogen receptors with a drug
like tamoxifen (Trade name: Nolvadex), which is often used to treat
estrogen-sensitive breast cancer. Another option is to suppress
estrogen secretion by using a GnRH analog -- leuprolide (Trade name:
Lupron.)
Normally, GnRH is secreted by the hypothalmus in a pulsatile fashion
to stimulate the anterior pituitary to secrete the hormone LH and FSH.
LH and FSH are also secreted in a pulsitile fashion and stimulate
estrogen synthesis by the ovaries. But it was discovered that when
GnRH is administered a continuous fashion (vs. pulsatile), LH and FSH
release is actually suppressed instead of stimulated, resulting in a
block of estrogen synthesis.
Eric Huang
UMDNJ - Robert Wood Johnson Medical School
Class of 2000
Here's a page out of the USP DI (Drug Information for the Helath Care
Professional)
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LEUPROLIDE (Systemic)
Revised: 08/06/93
VA CLASSIFICATION (Primary/Secondary)ľHS100/AN500
Commonly used brand name(s):
Lupron;
Lupron Depot.
Another commonly used name is leuprorelin.
Note: For a listing of dosage forms and brand names by country
availability, see Dosage Forms section(s).
Category
Gonadotropin-releasing hormone (GnRH) agonist; antineoplastic.
Indications
Accepted
Carcinoma, prostatic (treatment)ľLeuprolide is indicated for the
palliative treatment of advanced prostatic cancer, especially as an
alternative to orchiectomy or estrogen administration7,9.
Endometriosis (treatment)ľLeuprolide is indicated for management of
endometriosis, including pain relief and reduction of endometriotic
lesions8.
Pharmacology/Pharmacokinetics
Physicochemical characteristics:
SourceľSynthetic gonadotropin-releasing hormone (GnRH) analog8.
Molecular weightľ
1269.47
Mechanism of action/Effect:
Like naturally occurring luteinizing hormone-releasing hormone (LHRH),
initial2 or intermittent administration of leuprolide stimulates
release of luteinizing hormone (LH) and follicle-stimulating hormone
(FSH) from the anterior pituitary.
Prostatic carcinomaľLH and FSH release from the anterior pituitary
transiently increases testosterone concentrations in males. However,
continuous administration of leuprolide in the treatment of prostatic
carcinoma suppresses secretion of gonadotropin-releasing hormone, with
a resultant fall in testosterone concentrations and a "medical
castration."
EndometriosisľInitial stimulation of gonadotropins from the anterior
pituitary is followed by prolonged suppression8. Gonadotropin release
from the anterior pituitary transiently increases estrone and
estradiol concentrations in females7. However, continuous
administration of leuprolide in the treatment of endometriosis
produces a fall in estrogens to postmenopausal levels7,8. As a
consequence of suppression of ovarian function, both normal and
ectopic endometrial tissues become inactive and atrophic7. As a
result, amenorrhea occurs.
Other actions/effects:
Leuprolide also has some androgenic effects in females1.
Absorption:
Bioavailability after intramuscular injection of the depot
formulation is estimated to be about 90%8.
Protein binding:
Moderate (46%)8.
Onset of action:
Testosterone concentrationsľTransient increase occurs within first
week of therapy, but decline to castrate levels occurs within 2 to 4
weeks.
Time to peak effect:
AmenorrheaľUsually occurs after 1 to 2 months of therapy8.
Duration of action:
Pituitary-gonadal systemľNormal function is usually restored within 4
to 12 weeks after therapy is withdrawn8.
AmenorrheaľCyclic bleeding usually returns within 60 to 90 days after
therapy is withdrawn8.
Precautions to Consider
Cross-sensitivity and/or related problems
Patients sensitive to other synthetic GnRH analogs may also be
sensitive to leuprolide8.
Carcinogenicity
Studies in rats and mice for two years at daily subcutaneous doses of
0.6 to 4 mg per kg of body weight (mg/kg) and up to 60 mg/kg,
respectively, found only an increased incidence of benign pituitary
hyperplasia and benign pituitary adenomas at 24 months in the
rats7,8,9.
Mutagenicity
Mutagenicity studies in bacterial and mammalian systems found no
evidence of mutagenic effects7,8,9.
Pregnancy/Reproduction
FertilityľIn males: Suppression of testosterone secretion results in
impairment of fertility. Although it is not known whether fertility is
restored after leuprolide is withdrawn, reversal of fertility
suppression does occur after withdrawal of similar analogs.
PregnancyľLeuprolide is not recommended during pregnancy6.
Because the effects on fetal mortality would logically result from the
hormonal effects of leuprolide, it can be concluded that there is a
risk of spontaneous abortion if leuprolide is administered during
pregnancy6.
Use of nonhormonal contraception is recommended during treatment8.
Studies in rabbits at doses of 0.00024, 0.0024, and 0.024 mg/kg (1/600
to 1/6 the human dose) on day 6 of pregnancy found a dose-related
increase in major fetal abnormalities; these effects did not occur at
similar doses in rats. The two higher doses in rabbits and the highest
dose in rats were associated with increased fetal mortality and
decreased fetal weights.
FDA Pregnancy Category X6.
Breast-feeding
It is not known whether leuprolide passes into breast milk8. However,
because of potential adverse effects in the infant, breast-feeding is
usually not recommended during treatment with leuprolide8.
Geriatrics
Appropriate studies on the relationship of age to the effects of
leuprolide have not been performed in the geriatric population.
However, this medication is frequently used in elderly patients,
especially for treatment of prostatic carcinoma, and
geriatrics-specific problems that would limit the usefulness of this
medication in the elderly are not expected.
Laboratory value alterations
The following have been selected on the basis of their potential
clinical significance (possible effect in parentheses where
appropriate)ľnot necessarily inclusive (>> = major clinical
significance):
With physiology/laboratory test values
Acid phosphataseľ(transient increases in serum concentrations may
occur early in treatment of prostatic carcinoma, but usually decrease
to or near baseline by the fourth week)
Estrogenľ(serum concentrations are usually increased during the first
weeks of therapy for endometriosis but then decrease to postmenopausal
levels8)
Testosteroneľ(serum concentrations are usually increased during the
first week of therapy for prostatic carcinoma but then decrease;
castrate levels are reached within 2 to 4 weeks)
Medical considerations/Contraindications
The medical considerations/contraindications included have been
selected on the basis of their potential clinical significance
(reasons given in parentheses where appropriate)ľnot necessarily
inclusive (>> = major clinical significance).
Risk-benefit should be considered when the following medical problems
exist
Sensitivity to leuprolide4 or other GnRH analogs8ľ
For treatment of endometriosis
Osteoporosis, history ofľ(risk of loss of bone density may be
increased8)
>> Vaginal bleeding, undiagnosed abnormal8ľ
For treatment of prostatic carcinoma
>> Metastatic vertebral lesionsľ(worsening of symptoms during first few weeks of leuprolide therapy, with risk of neurologic problems, including paralysis7,9)
>> Urinary tract obstructionľ(worsening of symptoms during first few weeks of leuprolide therapy7,9)
Patient monitoring
The following may be especially important in patient monitoring (other
tests may be warranted in some patients, depending on condition; >>
= major clinical significance):
For treatment of endometriosis
Pregnancy test8ľ(recommended if treatment is not started during
menstruation or in patients with irregular cycles)
For treatment of prostatic carcinoma
Acid phophatase concentrations, serum and/orľ
Prostate-specific antigen (PSA) concentrations, serum10 and/orľ
Testosterone concentrations, serumľ(recommended at periodic intervals
to monitor response)
Side/Adverse Effects
Note: Many of the side/adverse effects of leuprolide are related to
hypoestrogenism in females and hypotestosteronism in males7,8,9.
There is a risk of increased loss of vertebral trabecular bone density
during treatment for endometriosis, some of which may be
irreversible8. However, the loss usually is small over the usual
6-month treatment period, except in patients with existing risk
factors (e.g., history of osteoporosis)8.
The following side/adverse effects have been selected on the basis of
their potential clinical significance (possible signs and symptoms in
parentheses where appropriate)ľnot necessarily inclusive:
Those indicating need for medical attention
Incidence less frequent
In both females and males
Cardiac arrhythmias or palpitations7,8,9 (fast or irregular heartbeat)
In females only
Androgenic effects8 (deepening of voice; increased hair growth)
In males only
Angina7,9 (chest pain)
Incidence rare
In males only
Myocardial infarction (pains in chest); pulmonary embolism (sudden
shortness of breath); thrombophlebitis (pains in groin or legs,
especially calves of legs)
Those indicating need for medical attention only if they continue or
are bothersome
Incidence more frequentľabove 50%
In both females and males
Hot flashes7,8,9 (sudden sweating and feelings of warmth)
In females only
Amenorrhea (stopping of menstrual periods)or spotting (light,
irregular vaginal bleeding)
Incidence less frequent
In both females and males
Blurred vision7,8; dizziness7,8; edema7,8 (swelling of feet or lower
legs); headache7,8; injection site reaction7,8 (burning, itching,
redness, or swelling at site of injection); nausea or vomiting7,8;
paresthesias7,9 (numbness or tingling of hands or feet); trouble in
sleeping7,8; weight gain7,9
In females only
Decreased libido8 (decreased interest in sex); disease flare,
transient (pelvic pain8); increased tenderness of breasts8; mood
changes8; vaginitis8 (burning, dryness, or itching of vagina)
Note: A disease flare, with a transient increase in symptoms (pelvic
pain, dysmenorrhea, dyspareunia, pelvic tenderness, induration), may
occur shortly after initiation of therapy for endometriosis, as a
result of the temporary increase in serum estradiol8.
In males only
Constipation7; decreased size of testicles7; disease flare, transient
(bone pain7,9); gynecomastia7 (swelling and increased tenderness of
breasts); impotence or decreased libido7,9 (inability to have or keep
an erection; decreased interest in sex); loss of appetite7
Note: A disease flare, with a transient, sometimes severe, increase
in bone or tumor pain, may occur shortly after initiation of therapy
for prostatic carcinoma, usually associated with the increase in serum
testosterone, but usually subsides with continued leuprolide
treatment. Analgesics may be required during this time. Other signs
and symptoms of prostatic carcinoma, including difficult urination and
spinal compression9, may also worsen transiently. In addition,
worsening of neurologic signs and symptoms in patients with vertebral
metastases may result in temporary weakness and paresthesias of the
lower extremities3; paralysis, with or without fatal complications, is
possible7,9; initiation of leuprolide therapy with daily
administration for the first 2 weeks to facilitate withdrawal of
treatment may be necessary in patients at risk7,9.
Patient Consultation
As an aid to patient consultation, refer to Advice for the Patient,
Leuprolide (Systemic).
In providing consultation, consider emphasizing the following selected
information (>> = major clinical significance):
Before using this medication
>> Conditions affecting use, especially:
Sensitivity to leuprolide or other GnRH agonists
PregnancyľPregnancy/reproductionľ
For males: May cause sterility
For females: Not recommended during pregnancy; causes birth defects in
animals; may cause spontaneous abortion
Other medical problems, especially undiagnosed abnormal vaginal
bleeding (for endometriosis) or urinary tract obstruction (for
prostatic carcinoma)
Proper use of this medication
>> Carefully reading patient instruction sheet contained in package
Using disposable syringes provided in kit
>> Importance of not using more or less medication than the amount prescribed
>> Importance of continuing medication despite side effects
>> Proper dosingMissed dose: For daily dosingľUsing as soon as remembered; not using if not remembered until next day; not doubling doses
>> Proper storage
Precautions while using this medication
>> Importance of close monitoring by the physician
For treatment of endometriosis
Possibility of amenorrhea or irregular menstrual periods; checking
with physician if regular menstruation does not occur within 60 to 90
days after discontinuation of medication
Advisability of using nonhormonal forms of contraception during
therapy; not using oral contraceptives
>> Stopping medication and checking with physician if pregnancy is suspected
Side/adverse effects
Signs of potential side effects, especially cardiac arrhythmias or
palpitations, androgenic effects in females, angina in males,
pulmonary embolism in males, thrombophlebitis in males, and myocardial
infarction in males
General Dosing Information
It is recommended that the intramuscular depot injection be
administered by the physician6.
Leuprolide has approximately 15 to 50 times the activity of naturally
occurring luteinizing hormone-releasing hormone (LHRH), and 80 to 100
times that of synthetic LHRH (gonadorelin).
For use in treatment of endometriosis
It is recommended that therapy begin with the first day of the
menstrual cycle after pregnancy has been ruled out.
Development of amenorrhea is usually evidence of a clinical response,
although spotting or bleeding from the atrophic endometrium can still
occur.
Therapy should be continued uninterrupted for 6 months8.
For use in treatment of prostatic carcinoma
Patients receiving leuprolide should be under supervision of a
physician experienced in cancer chemotherapy6.
Parenteral Dosage Forms
LEUPROLIDE ACETATE INJECTION
Usual adult dose
Prostatic carcinomaľ
Subcutaneous, 1 mg per day.
Strength(s) usually available
U.S.ľ
5 mg per mL (Rx)[Lupron (benzyl alcohol)].
Canadaľ
5 mg per mL (Rx)[Lupron (benzyl alcohol)].
Packaging and storage:
Store between 2 and 8 °C (36 and 46 °F) before dispensing and between
15 and 30 °C (59 and 86 °F) after dispensing, unless otherwise
specified by manufacturer. Protect from freezing. Protect from light.
Auxiliary labeling:
· Do not freeze.
LEUPROLIDE ACETATE FOR INJECTION
Usual adult dose
Prostatic carcinomaľ
Intramuscular, 7.5 mg once a month6.
Endometriosisľ
Intramuscular, 3.75 mg once a month8.
Strength(s) usually available
U.S.ľ
3.75 mg, with 1 ampul special diluent (Rx)[Lupron Depot (D-mannitol
6.6 mg) (purified gelatin) (DL-lactic and glycolic acids copolymer)
(diluent contains carboxymethylcellulose sodium 7.5 mg, D-mannitol 75
mg, polysorbate 80 1.5 mg, and acetic acid)].7.5 mg, with 1 ampul
special diluent (Rx)[Lupron Depot (D-mannitol 13.2 mg) (purified
gelatin) (DL-lactic and glycolic acids copolymer) (diluent contains
carboxymethylcellulose sodium 7.5 mg, D-mannitol 75 mg, polysorbate 80
1.5 mg, and acetic acid)].
Canadaľ
3.75 mg, with 1 ampul special diluent (Rx)[Lupron Depot].7.5 mg, with
1 ampul special diluent (Rx)[Lupron Depot (D-mannitol) (diluent
contains carboxymethylcellulose sodium 5 mg, D-mannitol 50 mg, and
polysorbate 80 1 mg)].
Packaging and storage:
Store between 15 and 30 °C (59 and 86 °F), unless otherwise specified
by manufacturer8,9. Protect from freezing.
Preparation of dosage form:
Leuprolide acetate for injection is reconstituted with 1 mL of diluent
provided by the manufacturer, shaking the suspension thoroughly to
evenly disperse particles8,9.
Stability:
Since leuprolide for injection and the diluent contain no
preservatives, the reconstituted suspension should be used immediately
after preparation and any unused portion should be discarded8,9.
Auxiliary labeling:
· Do not freeze.
References
Note: All references used in the development and earlier revisions of
this monograph have not yet been incorporated into the computer
database and, therefore, are not listed below. Citations for
information not yet referenced in the monograph will be provided upon
request.
1Lupron package insert (TAPľUS), Rev 4/85.
2Comments from TAP, 8/85.
3Panel comments, 1988 revision.
4General precaution per DID policy.
5Lupron package insert (TAPľUS), Rev 11/86.
6Lupron Depot package insert (TAPľUS), Rev 12/88.
7Lupron package insert (TAPľUS), Rev 1/90.
8Lupron Depot 3.75 mg package insert (TAPľUS), Rev 10/90.
9Lupron Depot 7.5 mg package insert (TAPľUS), Rev 1/90.
10Per panelist comments, 6/93.
11Wojciechowski NJ, Carter CA, Skoutakis VA, et al. Leuprolide: a
gonadotropin-releasing hormone analog for the palliative treatment of
prostatic cancer. Drug Intell Clin Pharm 1986 Oct; 20: 746-51.
12The management of clinically localized prostate cancer. National
Institutes of Health Consensus Development Conference Statement 1987
June 15-17; 6(10).
m2jit...@gmail.com
Another name of fibroid is Myoma. Uterine fibroid are non cancerous tumors in the body. These tumors are harmless, no need to worry but should remove from body. It could be large. I know a hospital where from you can take advice by personally meeting or mail. This is Jaslok Hospital in Mumbai - specialist hospital for Uterine myoma treatment. You can visit http://www.jaslokhospitalmrgfus.com/uterine_fibroid_treatment.html
m2jit...@gmail.com
> Can anyone advise me on a treatment for uterine fibroids called 'RH Gn
> sites or any info would be grately appreciated.
> Mike
Given url will solve your problem..
Please visit http://www.jaslokhospitalmrgfus.com/uterine_fibroid_treatment.html