Prostate cancer is an androgen-sensitive tumor. Currently, the treatment of advanced prostate cancer is based on hormone therapy. From June 1999 to August 2003, we conducted a comparative study on the changes of serum sex hormone levels before and after treatment of prostate cancer patients who underwent surgery (40 cases) or pharmacological debulking (22 cases).
I. Clinical data
There were 62 cases in this group. Age 50~84 years old, average 72 years old. The serum PSA ranged from 2.1 to 150.0 ng/m,l with an average of 24.8 ng/ml. 46 cases had abnormal rectal finger examination. Gleason score 2-4 in 15 cases, 6-7 in 28 cases and 8-10 in 19 cases. The patients were examined by rectal examination, transrectal ultrasound, CT, MRI and ECT, and the Whitmore-Jewett stage: 28 cases were C stage and 34 cases were D stage.
II. Methods
Surgical debridement (bilateral orchiectomy) was used in 40 cases, and pharmacological debridement (Inhibiton 3.75 mg or Noraid 3.6 mg, subcutaneous injection every 4 weeks, long-term application) was used in 22 cases. Serum testosterone (T), estradiol (E2), progesterone (P), follicle-stimulating hormone (FSH), luteinizing hormone (LH), and prolactin (PRL) levels were measured before and 1 and 3 months after treatment in the two groups, respectively. The electrochemiluminescence method was used, and the kit was from DPC, USA.
Discussion
Endocrine therapy for prostate cancer has been used for more than 60 years. There are two types of prostate cancer: androgen-dependent and androgen-independent, and the majority of prostate cancers are androgen-sensitive before endocrine therapy. The main goal of endocrine therapy for advanced prostate cancer is to eliminate androgens from the body.
LHRH-A is a synthetic luteinizing hormone-releasing hormone analogue, which is 100 times stronger than the LHRH produced by human body. The testosterone synthesis in Leydig cells is then reduced, and eventually the testosterone level decreases to the depot level, so it is called drug depot.
The use of LHRH-A in the treatment of prostate cancer is increasing because it is equally effective as surgical denervation, and it can avoid surgery and meet the needs of some patients who want to preserve the testes due to cosmetic or psychological factors, and it can be used for intermittent endocrine therapy.
It is important to study the sex hormone changes in prostate cancer patients after debulking to judge the efficacy and treatment response. Ying Jun et al. observed the changes of androgens in 16 patients with non-metastatic prostate cancer 5 days after surgical debulking, and the T decreased by 92. 3% compared with that before surgery. Zhang Liqing et al. found that in 15 cases of prostate cancer (stage B and D), serum T decreased to the depot level (<50 ng/L) 2 weeks after surgical debulking, and was stable at low levels when reviewed every 3 months afterwards.
The results of our study showed that serum T decreased by 94.8% compared with the preoperative level 1 month after debulking, and remained low until 3 months after surgery.
The serum T of patients with prostate cancer after drug debulking first increased transiently and then decreased rapidly. In six cases of stage D prostate cancer, the T increased rapidly after the application of Norad, reaching a peak on day 3, which was 1. 7 times of the basal value, and then decreased sharply, falling below the basal value on day 10, reaching the depot level in 3 weeks, and remained low.
In six cases of prostate cancer (stage B and D), serum T peaked on day 2-3 and started to decrease after 1 week, and then decreased to the depleted state at 4 weeks after the application of inhibition. The results of this study showed that 1 month after drug depot, serum T decreased by 94.7% compared to the pre-treatment level and reached depot level, and remained low 3 months after treatment. the difference in serum T values between the 2 groups at 1 and 3 months after treatment was not statistically significant.
Male estrogen is mainly produced from 3 sources:
(i) adrenal cortical secretion;
(ii) Aromatization of peripheral androgens;
(3) Testicular secretion: the supporting cells convert pregnenolone and progesterone into testosterone and aromatize testosterone into estradiol. Testicular interstitial cells also produce small amounts of estrogen.
After denervation, E2 from testicular and T aromatization is lost or reduced, resulting in a decrease in serum E2. In addition, after the decrease of T, the estrogen bound to sex hormone binding globulin (SHBG) increased, which also decreased the serum E2 level. In the present study, the decrease in serum E2 was greater in patients with pharmacological debulking than in those with surgical debulking. After surgical denervation, the negative feedback regulation of the hypothalamic-pituitary-gonadal axis increased the secretion of LH and FSH in the anterior pituitary gland due to the significant decrease in peripheral T. The serum LH and FSH levels increased 2. 4-fold and 5. 8-fold 1 month after surgical denervation, and remained at high levels until 3 months after surgery.
After drug depot, LH and FSH also showed a transient increase, and then gradually decreased to below the basal value around 7-10 d. The rise and fall of FSH was less significant than that of LH. In this study, FSH decreased by 50.9% and LH decreased by 93.3% at 1 month after drug depot, and the decrease of LH was greater than that of FSH. 3 months after treatment, FSH and LH remained at lower levels. The results of this study showed that both surgical and pharmacological debridement could significantly decrease P levels, but the decrease was greater in the pharmacological debridement group, while the debridement treatment had no significant effect on PRL levels.
The results of this study suggest that the effect of LHRH-A on prostate cancer may not only bring T to the level of denervation, but also significantly decrease FSH and LH levels, and the decrease of E2 and P is also greater than that of surgical denervation. The decrease in E2 and P secretion in the adrenal glands was caused by the negative feedback regulation of the central hypothalamus-pituitary-gonadal axis after surgical debulking, while the negative feedback of the central hypothalamus-pituitary-gonadal axis was blocked by drug debulking. Recently, it has been shown that prostate cancer cells express FSH receptors, LH receptors and LHRH receptors. The use of LHRH-A for recurrent metastases after surgical debulking of prostate cancer has been clinically reported to be still effective.
The study of sex hormone changes after prostate cancer debulking and related issues will help to further understand the effects of orchiectomy and LHRH-A application on prostate cancer.