ADT, targeted at achieving castrate level of serum testosterone, leads to a state of acute andropause with its attendant side effects and alteration in the metabolic profile of the patients. It is important to address these issues as not only the number of people getting ADT is increasing but also the duration of therapy which extends for longer periods, sometimes even over 10 years [9]. Several studies have documented alteration in the lipid profile of men started on ADT, but the results are not consistent and depend on the duration of treatment and the modality of the ADT.
In the present study, we observed statistically insignificant deterioration in the lipid profile parameters in patients who were treated with orchidectomy. Moorjani et al. reported similar changes in TG, LDL, VLDL, and HDL cholesterol levels following orchidectomy [10]. However, Ostergren et al., in a randomized comparative study including 57 patients, observed a significantly higher increase in the fat mass and body weight with orchidectomy compared to that of LHRHa [11]. Saglam et al., in a retrospective study including 44 patients, reported a significant increase in the total cholesterol, LDL, and TG at 12 months along with an increase in the HDL level for the first 3 months followed by a significant decline at 12 months. The difference between LHRHa and orchidectomy concerning the lipid profile was insignificant [12]. The inconsistency in the literature regarding the impact of orchidectomy on lipid profile might be due to different baseline BMI, small sample size, dietary habits, and socioeconomic status.
With LHRHa, we observed a significant increase in the mean total cholesterol, TG, and LDL cholesterol at 6 months followed by a return to the baseline at 12 months, and thereafter persisted at a similar level till 24 months. The mean VLDL level also increased significantly till 6 months and then showed a gradual decline till 24 months follow-up. Only the mean HDL cholesterol did not show a significant change during the study duration. Similar results were reported by Salvador et al. in a prospective study with LHRHa in 33 locally advanced and metastatic prostate cancer patients. They observed a significant increase in the total cholesterol [210–227 mg/dl (p < 0.05)] and LDL [132–148 mg/dl (p < 0.05)] with no significant change in HDL and TG levels at 6 months follow-up with the return of all lipid parameters to baseline at 12 months of follow-up [13]. In another prospective study, including 39 patients receiving LHRHa with or without bicalutamide, a significant increase was reported in the total cholesterol and LDL cholesterol starting at 3 months and the significant rise persisted till 9 months for total cholesterol and 12 months for LDL [14].
The difference in the impact of orchidectomy vs LHRHa on the lipid profile may be due to the different hormonal changes in either group: higher serum FSH, and LH, lower serum testosterone and estrogen with orchidectomy compared to low FSH and LH, and relatively higher estrogen with LHRHa. Also, in the absence of testosterone, serum FSH regulates the level of anti-Mullerian hormone levels [10, 15, 16]. However, the impact of the changes in the hormonal milieu on cardiovascular morbidity is not clearly defined as variable effects have been reported in the literature. Moorjani et al. observed a more favorable impact of LHRHa plus flutamide on lipoprotein profile and consequent cardiovascular disease compared to orchidectomy [10]. Sun et al. in a retrospective cohort study reported significantly higher cardiovascular events (p = 0.01) with gonadotropin-releasing agonist therapy compared to that of orchidectomy [15]. However, Thomsen et al. in an analysis of the prostate cancer population database found a similar 10-year crude probability of cardiovascular disease between medical and surgical castration [16]. In our study, though there was a significant but temporary deterioration in lipid profile with LHRHa and no significant alteration with orchidectomy, we did not observe any new onset clinical cardiovascular event during the 2 years of follow-up.
The results of this study may have an impact on the management of hyperlipidemia secondary to ADT among patients with prostate carcinoma. However, the results of this study are limited by the small sample size. We would like to recommend a prospective randomized study with a larger sample size to assess the impact of different modalities of ADT on lipid profile and consequent cardiovascular health parameters.
