Subcutaneous Depot Medroxyprogesterone Acetate versus Leuprolide Acetate in the Treatment of Endometriosis-Associated Pain

Abstract

BACKGROUND: A clinical study compared efficacy and safety of depot medroxyprogesterone acetate (DMPA) with leuprolide for endometriosis-associated pain. METHODS: This multicentre, 18 month, evaluator-blinded, comparatorcontrolled trial randomized 300 women with laparoscopically diagnosed endometriosis to 6 month treatment with subcutaneous injection of 104 mg/0.65 ml DMPA (DMPA-SC 104) every 3 months or leuprolide (3.75 mg monthly or 11.25 mg every 3 months), with 12 months post-treatment follow-up. Endpoints included patient response to treatment in five signs/symptoms (dysmenorrhoea, dyspareunia, pelvic pain, pelvic tenderness, induration) and changes in bone mineral density (BMD) and productivity at 6 and 18 months. RESULTS: DMPA-SC 104 and leuprolide produced equivalent (P < 0.02) reductions in at least four pain categories and significant (P < 0.001) improvements in composite score at months 6 and 18. At month 6, reductions in total hip and lumbar spine BMD were significantly less (P < 0.001) with DMPA-SC 104 versus leuprolide. BMD returned to pre-treatment levels 12 months post-treatment in the DMPA-SC 104 but not the leuprolide group. Total productivity also significantly (PՅ0.05) improved in both groups at 6 and 18 months. CONCLUSIONS: DMPA-SC 104 reduces endometriosis-associated pain as effectively as leuprolide and improves productivity with significantly less BMD decline.

Pharmacologic therapies in endometriosis: a systematic review

“…Limitations of GnRH-agonist therapy include the high recurrence rate (50% of patients show a relapse of symptoms within 6 months after therapy discontinuation) and side effects associated with the transitory pharmacologic menopause condition created: bone density loss, worsening of serum lipoprotein cholesterol distribution, depression, hot flashes, genitourinary atrophy, and decreased libido (135)(136)(137)(138)141). In adolescents treated with GnRH agonists, bone mineral density must be monitored with special care (140).…”

“…Oral contraceptives inhibit gonadal estrogen production through negative hypophyseal feedback (135)(136)(137). By suppressing ovarian activity, they may also reduce prostaglandin production secondary to endogenous estrogens and therefore decrease the inflammatory status (137).…”

“…By suppressing ovarian activity, they may also reduce prostaglandin production secondary to endogenous estrogens and therefore decrease the inflammatory status (137). Due to better tolerability and lower metabolic impact than GnRH agonists and danazol, cyclic and continuous OCPs are considered the first-line chronic treatment for endometriosis (135)(136)(137), either as a strategy to avoid surgery or as a postoperative adjuvant therapy to prolong the symptomfree interval (136,137).…”

Peptide Drugs

“…By causing constant stimulation of GnRH receptors, leuprolide initially causes stimulation, but thereafter decreases, by receptor downregulation, pituitary secretion of LH and FSH. Like other GnRH agonists, leuprolide may be used in the treatment of hormone-responsive cancers such as prostate cancer or breast cancer as well as estrogen-dependent benign disorders like endometriosis [13] or uterine fibroids, to treat precocious puberty [14] and to control ovarian stimulation in in vitro fertilization. (Figure 7.5) is a synthetic decapeptide that blocks the effects of GnRH (GnRH antagonist).…”

“…In 2003, it was found that tetra-branched forms of neurotensin and its short functional fragment neurotensin (8)(9)(10)(11)(12)(13) are stable for 24 h in human plasma and serum, and their receptor affinity is even higher than that of the corresponding monomeric peptides. The protease-resistant oligo-branched form of neurotensin appeared as a promising alternative to stabilized neurotensin monomeric sequences [55,56] for tumor targeting).…”