The Effect of Micronized Estradiol on Bone Turnover and Calciotropic Hormones in Older Men Receiving Hormonal Suppression Therapy for Prostate Cancer

Abstract

To examine the effect of estradiol (E(2)) without the confounding effect of hypothalamic-pituitary feedback, we studied men with prostate cancer in whom gonadotropin secretion was suppressed by LH-releasing hormone agonists (LHRH-A). Fourteen men over 65 yr of age and receiving established LHRH-A treatment (EST group) without bony metastases and 12 men who received LHRH-A as neoadjuvant therapy for locally advanced prostate cancer (NEO group) were randomized (double blind) to receive either 1 mg/d micronized E(2) (n = 12) or placebo (PL; n = 13) for 9 wk. E(2), estrone, testosterone, SHBG, PTH, and 25-hydroxy- and 1,25-dihydroxyvitamin D levels as well as markers of bone resorption [N- and C-telopeptide cross-links (NTX and CTX) and deoxypyridinoline] and bone formation (bone-specific alkaline phosphatase, osteocalcin, and N-terminal type I collagen) were measured before LHRH-A in the NEO group, before [baseline (BL)] and after 9 wk of E(2) or PL in all patients, and 6 wk after E(2) treatment in the EST group. In the NEO group, hormone levels fell 3 wk after the initial LHRH-A injection, and deoxypyridinoline increased significantly (P = 0.006). At BL, the EST group had higher bone turnover due to the longer duration of LHRH-A treatment. With E(2) treatment, E(2) levels rose into the normal male range, and two resorption markers decreased significantly from BL by 33% for NTX (P < 0.001) and 28% for CTX (P = 0.009). Bone formation markers did not change. PTH increased by 43% from BL (P < 0.01) in the E(2) group and decreased 16% from BL in the PL group (P < 0.01). Ionized calcium did not change in the E(2) group, but increased in the PL group by 2.3% (P < 0.01). NTX and CTX increased 6 wk after E(2) withdrawal in the EST group. We conclude that E(2) inhibits bone resorption in hypogonadal men through a direct skeletal effect that is independent of PTH. Low dose estrogen may be an option for the prevention and/or treatment of bone loss in this population.

Changes of Biochemical Markers of Bone Turnover and YKL-40 Following Hormonal Treatment for Metastatic Prostate Cancer Are Related to Survival

“…In contrast to bone formation markers, serum CTX-I was unchanged at this time point. In patients with localized PC, hormonal therapy increases the bone resorption markers urinary NTX-I (25 -27), urinary CTX-I (27), and serum ICTP (28) within 9 weeks to 6 months, whereas no effect was observed on the bone formation markers serum BAP, osteocalcin, and PICP. Thus, short-term hormonal therapy in men with PC leads to a general skeletal increase of bone resorption, which could mask its beneficial effects in reducing bone metastases activity when assessed by a systemic biochemical marker.…”

Androgen deprivation therapy for prostate cancer: new concepts and concerns

“…In a randomized controlled trial of 25 castrate men with nonmetastatic prostate cancer, estradiol (1 mg/day) decreased significantly biochemical markers of osteoclast activity after 9 weeks [51]. A small cross-sectional study reached similar conclusions [40].…”

Estradiol for the mitigation of adverse effects of androgen deprivation therapy

“…In a pilot RCT of E 2 add-back in men receiving LHRHa, men were given 9 weeks of therapy with oral E 2 (1 mg/ day) or placebo (Taxel et al 2002). At baseline men had low but detectable E 2 associated with castrate testosterone levels, measured by immunoassay.…”