Analysis of the clinical efficacy of leuprolide acetate in the treatment of obese patients with endometriosis and its role on the expression of MIF gene

Endometriosis is an invasive but benign disease of women that develops in endometrial glands outside the endometrium and uterine muscle. It affects about 15-20% of women of childbearing age. One effective way to treat endometriosis is to use GnRH agonists, which inhibit estrogen production. However, one of the possible side effects of this treatment is obesity and BMI increasing, which is a concern for some patients. This study investigated the role of leuprolide acetate in treating overweight patients (BMI≥30) and their comparison with non-overweight patients (BMI<30) for six months. Also, the effect of this medicine was evaluated on the expression of the MIF gene, which is an effective gene in obesity. For this purpose, a clinical trial was performed on 75 women with endometriosis aged 18 to 35 years. These patients were divided into two groups. The first group consisted of 38 patients with BMI<30. The second group consisted of 37 patients with BMI≥30. Both groups were treated with leuprolide acetate at a dose of 3.75 mg/month (intramuscularly) for six months. In addition to clinical evaluations, the expression of the MIF gene was assessed by the real-time PCR technique. The results showed that treatment with leuprolide acetate during six months in both groups reduced dysmenorrhea, dyspareunia, and chronic pelvic pain (P<0.05). Although this decrease was greater in the BMI <30 group, the difference was not significant. Also, after collecting the side effects of the medication, it was found that hypoestrogenism, such as cramps and spotting, was more in the first group; Endogenous complications such as oily skin, acne, and hirsutism were also more common in the second group. The results of MIF gene expression showed that the expression level before and after the start of the experiment in the second group (BMI≥ 30) is higher than the first group (BMI <30). The results also showed that the two groups increased the expression of the MIF gene after treatment with leuprolide acetate. This increase was statistically significant in the second group (P = 0.042). Generally, it was found that this medication causes more weight gain in obese people and increases the risk of obesity-related diseases among these patients. Therefore, it is recommended that this treatment be used with caution in obese patients with endometriosis.

Ulipristal Acetate Versus Leuprolide Acetate in Medical Management of Uterine Fibroids

BACKGROUND We wanted to compare the effectiveness of the treatment and the adverse effects of ulipristal acetate and leuprolide acetate in the medical management of symptomatic uterine fibroids. METHODS This is a randomised controlled study conducted in the the Department of Obstetrics and Gynaecology in Chalmeda Anand Rao Institute of Medical Sciences from January 2019 to January 2020. 60 patients with symptomatic fibroids and excessive uterine bleeding were randomly divided. They were given daily therapy of ulipristal acetate 10 mg orally for 3 months or monthly injection leuprolide acetate 3.75 mg intramuscularly for 3 months. RESULTS Controlled uterine bleeding was observed in 98 % of patients who received oral therapy of ulipristal acetate of 10 mg, and 89 % of patients who received injections of leuprolide acetate, for differences in comparison with leuprolide acetate of 8.8 % points (95 % CI, 0.4 to 18.3) for ulipristal acetate of 10 mg. Median time of amenorrhea for those taking ulipristal acetate of 10 mg was 5 days, and 21 days for leuprolide acetate. 10 % of patients receiving ulipristal acetate reported moderateto-severe hot flashes and 40 % of patients receiving leuprolide acetate reported moderate to severe hot flashes (P < 0.0010 for each dose of leuprolide acetate vs. ulipristal acetate). CONCLUSIONS Daily therapy of 10-mg ulipristal acetate was considered non inferior when compared to monthly injections of leuprolide acetate in control of uterine bleeding, moreover ulipristal acetate therapy was also significantly less likely to cause hot flashes. KEY WORDS Ulipristal Acetate; Leuprolide acetate; Abnormal Uterine Bleeding; Leiomyoma

Fabrication and Release Kinetics of Liposomes Containing Leuprolide Acetate

The present work is focused on the preparation and in vitro release kinetics of liposomal formulation of Leuprolide Acetate. In this work, “Thin Lipid Film Hydration Method” was used for preparation of Leuprolide Acetate loaded liposomes. Prepared liposomal formulations of Leuprolide acetate was evaluated by drug entrapment study, in-vitro drug release kinetics and stability studies. The percentage drug entrapment of Leuprolide acetate for F1 and F2 formulations were found to be 78.14 ± 0.67 and 66.70 ± 0.81% respectively. In-vitro drug release study of liposomal formulations had shown zero order release pattern. Regression co-efficient (R2) value of Zero order kinetics for F1 and F2 formulations were 0.9912 and 0.9676 respectively. After storing formulations for 1 month, stability testing was done at 40C.It was found that all batches were stable. These liposomal formulations of Leuprolide acetate can be formulated for parenteral application to treat prostate cancer and in women, to treat symptoms of endometriosis (overgrowth of uterine lining outside of the uterus) or uterine fibroids.

Relugolix, an oral gonadotropin-releasing hormone antagonist for the treatment of prostate cancer

Androgen deprivation therapy using gonadotropin-releasing hormone (GnRH) analogues is standard treatment for intermediate and advanced prostate cancer. GnRH agonist therapy results in an initial testosterone flare, and increased metabolic and cardiovascular risks. The GnRH antagonist relugolix is able to reduce serum testosterone levels in men with prostate cancer without inducing testosterone flare. In the HERO Phase III trial, relugolix was superior to leuprolide acetate at rapidly reducing testosterone and continuously suppressing testosterone, with faster post-treatment recovery of testosterone levels. Relugolix was associated with a 54% lower incidence of major adverse cardiovascular events than leuprolide acetate. As the first oral GnRH antagonist approved for the treatment of advanced prostate cancer, relugolix offers a new treatment option.