Chest
Volume 133, Issue 2, February 2008, Pages 448-454
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Original Research
Interstitial Lung Disease
Effect of a Gonadotrophin-Releasing Hormone Analogue on Lung Function in Lymphangioleiomyomatosis

https://doi.org/10.1378/chest.07-2277Get rights and content

Background

Lymphangioleiomyomatosis (LAM), a multisystem disease occurring primarily in women, is characterized by cystic lung destruction, and kidney and lymphatic tumors, caused by the proliferation of abnormal-appearing cells (ie, LAM cells) with a smooth muscle cell phenotype that express melanoma antigens and are capable of metastasizing. Estrogen receptors are present in LAM cells, and this finding, along with reports of disease progression during pregnancy or following exogenous estrogen administration, suggest the involvement of estrogens in the pathogenesis of LAM. Consequently, antiestrogen therapies have been employed in treatment. The goal of this prospective study was to evaluate the efficacy of triptorelin, a gonadotrophin-releasing hormone analogue, in 11 premenopausal women with LAM.

Methods

Patients were evaluated at baseline and every 3 to 6 months thereafter, for a total of 36 months. Hormonal assays, pulmonary function tests, 6-min walk tests, high-resolution CT scans of the chest, and bone mineral density studies were performed.

Results

Gonadal suppression was achieved in all patients. Overall, a significant decline in lung function was observed; two patients underwent lung transplantation 1 year after study enrollment, and another patient was lost to follow-up. Treatment with triptorelin was associated with a decline in bone mineral density.

Conclusions

Triptorelin appears not to prevent a decline in lung function in patients with LAM. Its use, however, may be associated with the loss of bone mineral density.

Section snippets

Study Population

This study evaluated the response to treatment with triptorelin, a synthetic analogue of Gn-RH (11.25 mg IM every 3 months) in 11 premenopausal LAM patients. Informed consent was obtained from all patients, and the protocol was approved by the San Giuseppe Hospital Institutional Review Board.

Study Design

Patients were evaluated at baseline, and at 3, 6, 12, 18, 24, and 36 months after initiating therapy. Routine blood testing and hormonal assays (ie, for FSH, LH, 17 β-estradiol, and total testosterone) were

Characteristics of the Patients

Of the 11 patients (mean age, 37 ± 7 years; age range, 24 to 49 years), 9 had a histologically proven diagnosis of LAM, and 2 patients exhibited clinical and radiographic features consistent with LAM. Radiographic features consisted of the presence of thin-walled cysts scattered throughout the lungs combined with abdominal angiomyolipomas and/or lymphangioleiomyomas.2 Three patients were ex-smokers; the remaining patients were nonsmokers. One patient had LAM/TSC. Four patients had renal

Discussion

The goal of this study was to evaluate the effect of treatment with triptorelin, a Gn-RH analogue, on lung function in patients with LAM. Although triptorelin was effective in suppressing ovarian function, all but 1 of the 10 patients who completed the study experienced a decline in FEV1; a reduction in Dlco was observed in all patients. In two cases, an accelerated loss of lung function resulted in lung transplantation. Only one patient showed improvement in FEV1 and 6MWT distance, despite

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    Supported in part by the Intramural Research Program, National Institutes of Health, National Heart, Lung, and Blood Institute.

    The authors have reported to the ACCP that no significant conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

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