<b>leuprolide acetate [Lupron Depot]</b>

Gonadotropin-releasing hormone agonist [GnRHa] therapy essentially shuts down ovarian production of hormones. In the premenopausal woman with a hormone sensitive tumor, GnRHa therapy could prevent hormonal stimulation of the tumor.

<b>Accidental Use in Presence of LMS </b> 
Leuprolide acetate [Lupron Depot] has been used to decrease uterine size and shrink leiomyomata [uterine fibroids]. In carefully selected patients, it is very useful. 

But what if leuprolide acetate is inadvertently given to a patient with an unsuspected leiomyosarcoma? One patient treated for leiomyomata with monthly injections of leuprolide acetate had increased bleeding, aborting mass, urinary problems and severe pain in the third month, requiring an immediate operation. 

Gonadotropin-releasing hormone [GnRH] agonist therapy may palliate symptoms and delay definitive surgical therapy of leiomyosarcoma, resulting in more advanced disease at diagnosis, with resulting effect upon patient survival. Similar cases will continue to raise arguments against conservative hormonal intervention in the perimenopausal woman with an enlarged uterus. 

As the use of GnRH agonists in the treatment of fibroid uterus increases, the potential for delay in the diagnosis and treatment of sarcomatous disease will become more common. Physicians must be aware of this potential complication of conservative therapy of uterine fibroids.


<b>Use to Prevent Estrogen Stimulation of Breast Cancer</b> 
Gonadotropin-releasing hormone agonist [GnRHa] therapy essentially shuts down ovarian production of hormones. In the <b>premenopausal woman</b> with a hormone sensitive tumor, GnRHa therapy can help prevent hormonal stimulation of the tumor. Premenopausal patients after primary surgery showed the best response during the GnRH agonist treatment. 

Treatment is well tolerated. The main side effects (hot flushes, increased sweating, headache etc.) were related to estrogen suppression. Leuprolide acetate-depot is a safe and effective palliative drug for pre- and perimenopausal metastatic breast cancer patients. 
Like other GnRH-agonists which have been evaluated for this indication, leuprolideacetate-depot can be used as first-line endocrine treatment in these patients. [GnRH agonists have lowered serum testosterone, suggesting that androgens in post-menopausal women may be partly produced by the ovaries. This fall in testosterone may explain why some post-menopausal breast cancer patients have been reported to respond to treatment with GnRH agonists, as it would decrease the androgens that are converted into estrogen. However, it would be likely that the aromatase inhibitors would be more potent estrogen inhibitors in the post-menopausal cancer patient.] 


<b>Use to Prevent Estrogen Stimulation of Endometrial Cancer</b> 
Endometrial cancer patients usually have complete hysterectomies, removing ovaries as well as other bits and pieces. So, most LMS patients with endometrial cancer have gone through a surgically induced menopause, and aromatase inhibitors would be the drug of choice for their estrogen sensitive tumors. GnRH agonists do shut down ovarian production of hormones. For this reason, GnRH agonists would be best used in the PRE menopausal patient, where the major source of estrogen is ovarian. 

Or in ovarian cancer patients, to prevent stimulation of the tumor by LH and FSH. There is one clinical trial of Lupron Depot reported in PubMed, published in 1997. Of 25 patients, there were no responders, but 8 patients had stable disease for a median 5 months [range 1 to 8]. They concluded that leuprolide does not appear to be a clinically active agent in the treatment of recurrent or metastatic endometrial cancer. However, the median age at study entry was 62 years. It is unlikely that the majority of patients in this study were peri or pre menopausal. One would rather use as subjects for this experiment pre-menopausal women whose tumors are positive for hormone receptors, and whose ovaries were still present and working. 

<b>So Lupron Depot might be useful for cancer treatment in LMS. Its use would probably be limited to two groups of people: 
a) people with ovarian LMS, b) those whose ovaries are still present and working, and whose LMS [of whatever primary] is positive for a hormone receptor.</b>

It is noted that there has been a report of endometrial adenocarcinoma in two patients shortly after suspending GnRH-agonist treatment for menometrorrhagia and uterine fibromata. When being treated with Lupron Depot, symptoms of severe hypoestrogenism can surface. Not only bone demineralization, hot flashes, sweating & headache, and sex organ problems, but also problems with cognition and mood. When women are treated with Lupron Depot for uterine fibroids for long periods, sometimes an "add back" regimen of weak estrogens is given.

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