Toward Removing Uterine Fibroids without Surgery: Subcutaneous Infusion of a Luteinizing Hormone-Releasing Hormone Agonist Commencing in the Luteal Phase

Abstract

Intermittent sc injection of a LHRH agonist reduced uterine fibroid size in 5 women. Commencement of the LHRH agonist buserelin on day 21 of the menstrual cycle induced a marked increase in plasma LH and FSH concentrations, followed by rises in estradiol (E2) and progesterone. LH and FSH levels fell to within the normal range by 120 h after beginning buserelin, despite continuing administration of the agonist. After menstruation, marked sustained suppression of cyclical gonadotropin and steroid concentrations occurred: mean values of FSH, LH, and E2 were 4.9 +/- 0.5 (+/- SE) mIU/ml, 5.9 +/- 0.6 mIU/ml, and 47.9 +/- 10.8 pg/ml, respectively, during the 20 weeks of buserelin treatment. During treatment, E2 concentrations remained below 50 pg/ml in 98 of 116 weekly observations. Uterine fibroids shrank after 8 or 10 weeks of buserelin administration, as assessed by ultrasound or gynecological examination. Compared to their initial volume, mean uterine fibroid volume after 20 weeks of buserelin infusion decreased from 220 +/- 51 to 98 +/- 26 cm3, which was 39.4 +/- 6.9% of the pretreatment volume. We conclude that sc administration of a LHRH agonist beginning in the luteal phase markedly reduced the size of uterine leiomyomata, suppressed, but did not abolish, pituitary and ovarian function, and warrants further evaluation as an option or adjunctive therapy to uterine myomectomy or hysterectomy.

Absence of Immunoreactive Luteinizing Hormone following Gonadotropin-Releasing Hormone Agonist Therapy in Women with Endometriosis

“…Using the monoclonal-anti body-based immunoradiometric assay, we found no immunoreactive LH after 6 weeks of GnRH agonist therapy. This result is in good agreement with the very low estradiol levels measured during this period by us or reported by others [1,4,6,7],…”

“…This initial rise is followed by a de crease of gonadotropins to baseline values (4-8 mlU/ml) and a concomitant decrease of estradiol to levels usually below 50 pg/ml. Even after extended treatment peri ods (up to 116 weeks), pituitary function, as determined by LH levels, was not com pletely abolished [4], Also in normal women with ovulatory cycles, DeFazio et al [3] were unable to detect a decrease in LH levels despite a significant fall of FSH concentrations occurring after 14 days of GnRH agonist administration. These re sults as well as clinical evidence indicate that sustained treatment with GnRH ago nists most likely abolishes pituitary func tion, in spite of the fact that gonadotropin radioimmunoassays based on polyclonal an tibodies do not show this effect.…”

“…1], These properties of GnRH agonists have led to several clinical applications in gynecolo gy, pediatric endocrinology and andrology. GnRH agonist therapy has been used to treat hirsutism [2], polycystic ovarian disease [3], uterine fibroids [4], breast cancer [5], pre cocious puberty [6,7] and endometriosis [8,9], Clinical studies in which FSH and LH concentrations were measured during GnRH agonist therapy have shown that an acute rise in serum gonadotropin occurs within days after the administration of the drug. This initial rise is followed by a de crease of gonadotropins to baseline values (4-8 mlU/ml) and a concomitant decrease of estradiol to levels usually below 50 pg/ml.…”

Submucous myomas: diagnosis and therapy

“…Although many drugs have been studied, clinically only GnRH analogues are capable of significantly reducing the size of myomas, with percentages between 30 and 70, when these had been used for 3 to 4 months preceding surgical intervention [61][62][63][64][65][66]. Although, in these studies, no distinction is made in fibroid location and no endoscopic procedures were involved, it seems that part of the results may be extrapolated to be applied to submucous myomas and TCRM as well.…”

Paclitaxel Promotes Cell Apoptosis in Uterine Leiomyomas

“…Uterine leiomyomas, also known as uterine myomas, pose an important problem to women's health [1,2,3]. They commonly cause severe symptoms such as heavy, irregular anemia and prolonged menstrual bleeding.…”