leuprolide and Osteoporosis

Treatment for cancer may cause gonadal dysfunction and bone loss (cancer treatment-induced bone loss ; CTIBL) . Especially, endocrine therapies for breast cancer or prostate cancer carry a significant risk of CTIBL. Therapy-induced premature menopause in premenopausal breast cancer patients, aromatase inhibitor in postmenopausal breast cancer patients, and LHRH agonist with or without anti-androgen in prostate cancer patients may cause bone loss of 5% or more. RANKL (receptor activator of nuclear factor-κB ligand) antibody (denosumab) is effective for prevention of CTIBL and it may prevent CTIBL-induced fracture. During cancer treatment with gonadal dysfunction, bone mineral density should be carefully followed to avoid QOL impairment due to osoteoporosis.

Topics: Androgen Antagonists; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Agents; Aromatase Inhibitors; Denosumab; Fractures, Bone; Gonadotropin-Releasing Hormone; Goserelin; Humans; Leuprolide; Osteoporosis; RANK Ligand; Selective Estrogen Receptor Modulators

S.R., a 65-year-old male with a history of prostate cancer, went to a cancer center in 2003. He had developed symptoms of bladder outlet obstruction in 1999 and was seen by a urologist. His baseline prostate-specific antigen (PSA) was 44 ng/ml. On physical examination, his prostate was enlarged, and a biopsy in January 2000 revealed adenocarcinoma with a Gleason score of 8. A metastatic workup, including a bone scan and a computed tomography scan of the abdomen and pelvis (CT A/P), was negative for evidence of metastatic disease. S.R. received conformal external beam radiation, and the luteinizing hormone-releasing hormone agonist leuprolide acetate was initiated. Following treatment, his PSA nadired to 0.2 ng/ml, and he did well until 2002, when his PSA started to rise. A reevaluation CT A/P revealed enlarged retroperitoneal and pelvic lymph nodes, and a bone scan was positive for metastatic disease. He underwent a bilateral orchiectomy in November 2002.

Topics: Adenocarcinoma; Aged; Androgen Antagonists; Antineoplastic Agents, Hormonal; Bone Density Conservation Agents; Combined Modality Therapy; Diphosphonates; Gonadotropin-Releasing Hormone; Humans; Imidazoles; Jaw Diseases; Leuprolide; Male; Orchiectomy; Osteonecrosis; Osteoporosis; Prostate-Specific Antigen; Prostatic Neoplasms; Radiotherapy, Conformal; Risk Factors; Tomography, X-Ray Computed; Zoledronic Acid

With the increasing indications for the use of androgen-deprivation therapy in the treatment of men with prostate cancer, side effects of the therapy deserve greater attention. Side effects such as hot flashes, decreased libido, decreased sexual function, and fatigue primarily affect the patients quality of life. Other side effects such as osteoporosis and changes in lipid profiles may also affect the patients overall health. Treatments such as estrogen, megestrol acetate, antidepressants, and bisphosphonates are useful in the management of many of the deleterious side effects of androgen deprivation. In addition, alternative management strategies such as intermittent androgen ablation and antiandrogen monotherapy may be useful in minimizing side effects caused by androgen ablation. Patients and physicians should be well aware of the potential side effects of androgen-deprivation therapy as well as the preventive and treatment strategies for these side effects in order to improve patients quality of life and health.

Topics: Androgen Antagonists; Antineoplastic Agents, Hormonal; Diphosphonates; Hot Flashes; Humans; Leuprolide; Male; Osteoporosis; Prostatic Neoplasms; Quality of Life

It has generally been held that estrogen and testosterone are the major sex steroids regulating bone metabolism in women and men, respectively. However, the description of several "experiments of nature" led to a reconsideration of this notion. Thus, a male carrying homozygous mutations in the ER-alpha gene and two males with homozygous mutations in the aromatase gene had osteopenia, unfused epiphyses, and elevated indices of bone turnover. Though these findings indicated that estrogen plays a role in regulating the male skeleton, they left unresolved the issue of whether estrogen acted on the male skeleton mainly to enhance bone mass acquisition during growth and maturation, or whether it also acted to retard bone loss in aging individuals. To address this issue, several cross-sectional observational studies have related bone mineral density (BMD) to sex steroids in elderly men, and found that estrogen correlated better than testosterone with BMD. In addition, recent longitudinal studies from our group indicate that bioavailable estrogen correlated better than testosterone both with the gain in BMD in young men and with loss of BMD in elderly men. These observational studies do not, however, prove causality, which requires direct interventional studies. Thus, we eliminated endogenous testosterone and estrogen production in 59 elderly men (mean age 68 years), studied them first under conditions of physiologic testosterone and estrogen replacement, and then assessed the impact on bone turnover of withdrawing both testosterone and estrogen, withdrawing only testosterone, only estrogen, or continuing both. We found that estrogen played the major role in regulating bone resorption in these men, and that both estrogen and testosterone were important in maintaining bone formation. Collectively then, these findings indicate that estrogen plays a dominant role in regulating the male skeleton.

Topics: Adult; Aged; Aged, 80 and over; Amino Acids; Bone Density; Collagen; Collagen Type I; Cross-Sectional Studies; Estrogens; Humans; Leuprolide; Longitudinal Studies; Male; Middle Aged; Osteocalcin; Osteoporosis; Peptide Fragments; Peptides; Procollagen; Testosterone

Topics: Buserelin; Endometriosis; Estradiol; Female; Gonadotropin-Releasing Hormone; Humans; Leuprolide; Nafarelin; Osteoporosis

Mitogenesis and mutagenesis are major driving forces in neoplastic development. Little is known about important breast mutagens, but much is known about breast mitogens. "Blocking" the effect of breast cell mitogens, by reducing the actual exposure of the breast to them, is an obvious strategy for breast cancer prevention. The ovarian hormones, estrogens and progesterone, are major effective (direct or indirect) breast cell mitogens. There is overwhelming epidemiologic evidence that breast cancer risk is closely related to exposure to estrogens and progestogens. A woman's exposure to endogenous ovarian estrogens and progesterone is drastically reduced by the use of combination-type oral contraceptives (COCs), but the exogenous synthetic estrogen and progestogen in the COC effectively replace the ovarian estrogen and progesterone, so that no decrease in breast cell exposure to these hormones is obtained. Doses of estrogen and progestogen in modern COCs are close to the minimum attainable, while still retaining both contraceptive efficacy and ovarian suppression (so that endogenous estrogen and progesterone do not add to the dose of estrogen and progestogen from the COC). Considerably lower effective breast cell exposure to estrogen and progestogen can, however, be achieved by using a gonadotropin-releasing hormone agonist to suppress ovarian function and compensating for the resulting hypoestrogenemia with low-dose hormone replacement. Such a contraceptive is predicted to reduce lifetime breast cancer risk by more than 50% if used for 10 years and by as much as 70% following 15 years of use. Contraception represents a unique opportunity to have a substantial beneficial impact on women's health; more than 10 million women use COCs daily in the United States.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Age Factors; Bone Density; Breast Neoplasms; Cardiovascular Diseases; Case-Control Studies; Cell Division; Contraceptives, Oral, Combined; Contraceptives, Oral, Hormonal; Drug Utilization; Endometrial Neoplasms; Endometrium; Estrogen Replacement Therapy; Estrogens; Female; Gonadotropin-Releasing Hormone; Humans; Hyperplasia; Incidence; Leuprolide; Middle Aged; Neoplasms, Hormone-Dependent; Osteoporosis; Ovarian Neoplasms; Pilot Projects; Premenopause; Progesterone; Progestins; Reproductive History; Risk Factors; Testosterone

To assess the effects of timing and schedule of zoledronic acid (ZA) administration on bone mineral density (BMD) in patients beginning androgen deprivation therapy (ADT) for the treatment of recurrent prostate cancer.. In this randomized, 3-arm trial, we evaluated changes in BMD after 3 different ZA administration schedules in men with recurrent prostate cancer who were beginning ADT. Forty-four patients were enrolled and randomized to receive a single dose of ZA given 1 week before beginning ADT (arm 1), a single dose of ZA given 6 months after beginning ADT (arm 2), or monthly administration of ZA starting 6 months after beginning ADT, for a total of 6 doses (arm 3).. Patients who received ZA before ADT had a significant improvement in BMD at the total proximal femur and trochanter after 6 months compared with the other groups. In addition, only patients in the arm that received multiple doses improved lumbar spine BMD while on ADT, with these findings persisting to 24 months. However, this group also experienced more grade 1 adverse events.. Analysis of these data suggests that ZA administration before initiation of ADT was superior to treatment 6 months after starting ADT in maintaining BMD. In addition, monthly ZA administration can increase BMD above baseline but is associated with more adverse events. Further study is needed to examine whether the timing and frequency of ZA therapy in patients on ADT can reduce fracture risk.

Topics: Aged; Alkaline Phosphatase; Androgen Antagonists; Bone Density; Bone Density Conservation Agents; Cell Proliferation; Diphosphonates; Drug Administration Schedule; Goserelin; Humans; Imidazoles; Leuprolide; Lymphocyte Count; Male; Middle Aged; Osteoporosis; Prostate-Specific Antigen; Prostatic Neoplasms; T-Lymphocytes; Zoledronic Acid

Androgen-deprivation therapy (ADT) induces loss of bone mineral density (BMD) and increases the risk of fractures in patients with prostate cancer (PCa). We sought to determine whether a weekly dose of alendronate, an oral bisphosphonate, could reduce this unwanted side-effect.. To assess whether once-weekly oral alendronate therapy would maintain or improve BMD in men initiating ADT for localised PCa.. A multicentre, double-blind, randomised, placebo-controlled study, we included hormonally naïve PCa patients initiating ADT with leuprolide acetate 30 mg intramuscularly every 4 mo.. Patients were randomised to receive either oral alendronate 70 mg once weekly or placebo for 1 yr. Both groups received daily calcium 1g and vitamin D 400 international units.. Changes in BMD (at the lumbar spine [LS] and total hip [TH]) and bone markers.. One hundred ninety-one subjects were enrolled, and 186 were randomised between alendronate (n=84) and placebo (n=102). The alendronate group demonstrated a mean spine BMD increase of 1.7% compared with -1.9% in the placebo group (p<0.0001). Alendronate also increased the BMD at the hip (percent change: 0.7%) compared to placebo (-1.6%). Median urinary N-terminal crosslinking telopeptide of type I collagen (Ntx) values decreased by 3.5% in the alendronate group and increased by 16.5% in the placebo arm, even after adjusting for centre (p=0.510) and baseline urinary Ntx (p<0.0001). Bone-specific alkaline phosphatase (BSAP) decreased a median of 2.25% in the alendronate group and increased a median of 3.12% in the placebo arm, regardless of centre or baseline BSAP or other covariates (p<0.0001). The safety and tolerability profile was similar for the two treatment groups.. Although the study was closed early because of slow accrual, it showed that weekly oral alendronate prevented bone loss and increased bone mass in addition to decreasing bone turnover in patients initiating ADT for localised PCa, with few related side-effects.

Topics: Absorptiometry, Photon; Administration, Oral; Aged; Aged, 80 and over; Alendronate; Alkaline Phosphatase; Analysis of Variance; Androgen Antagonists; Antineoplastic Agents, Hormonal; Biomarkers; Bone Density; Bone Density Conservation Agents; Canada; Chi-Square Distribution; Collagen Type I; Double-Blind Method; Drug Administration Schedule; Hip Joint; Humans; Injections, Intramuscular; Leuprolide; Lumbar Vertebrae; Male; Middle Aged; Osteoporosis; Patient Selection; Peptides; Predictive Value of Tests; Prostatic Neoplasms; Time Factors; Treatment Outcome

To investigate changes in bone mineral density (BMD) and fracture risk in men who received intermittent androgen deprivation (IAD) for nonmetastatic, hormone-sensitive prostate cancer.. Men with prostate cancer who lacked radiographically detectable metastases were treated in a prospective trial of IAD. After 9 months of treatment with leuprolide and flutamide, androgen deprivation therapy (ADT) was stopped until prostate-specific antigen reached a threshold (1 ng/mL for radical prostatectomy; 4 ng/mL for radiation or primary ADT) for a new cycle. Dual-energy x-ray absorptiometry (DXA) scans were performed before starting ADT and subsequently with each change in therapy. At least two consecutive DXA scans were required for this analysis. Computed tomography, bone scintigraphy, and lumbar spine x-rays were performed at the beginning and end of each treatment period.. Fifty-six of 100 patients met criteria for this analysis. The median age at study entry was 64.5 years (range, 49.8 to 80.9 years). The average percentage change in BMD during the first on-treatment period was -3.4% (P < .001) for the spine and -1.2% (P = .001) for the left hip. During the first off-treatment period (median, 37.4 weeks; range, 13.4 weeks to 8.7+ years), BMD recovery at the spine was significant, with an average percentage change of +1.4% (P = .002). Subsequent periods had heterogeneous changes of BMD without significant average changes. After a median of 5.5 years (range, 1.1 to 13.8+) years on trial, one patient (1.8%) had a compression fracture associated with trauma.. Patients experienced the greatest average change in BMD during early treatment periods of IAD with a smaller average change thereafter. Fractures were rare.

Topics: Absorptiometry, Photon; Aged; Aged, 80 and over; Androgen Antagonists; Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Bone Density; Bone Diseases, Metabolic; Drug Administration Schedule; Flutamide; Fractures, Bone; Humans; Leuprolide; Linear Models; Male; Middle Aged; Multivariate Analysis; Neoplasms, Hormone-Dependent; Osteoporosis; Prospective Studies; Prostatic Neoplasms; Risk Assessment; Risk Factors; Time Factors; Tomography, X-Ray Computed; Treatment Outcome

To investigate changes in bone mineral density (BMD) and osteoporosis, over 3 years of intermittent androgen-suppression therapy (IAST).. This was a Phase II individual cohort study of 72 patients with prostate cancer without metastatic bone disease, enrolled between 1999 and 2002. Patients had 9 months flutamide (250 mg, three times daily) and leuprolide (22.5 mg, 3-monthly depot) after which, patients ceased therapy providing that their PSA levels were <4 ng/mL. AST re-commenced when the PSA level exceeded the pretreatment level or was >20 ng/mL. BMD for hip and spine was the primary endpoint; assessed at baseline; completion of initial treatment period; and at 1 and 2 years after initial treatment (POST period).. Osteoporosis increased from 7% at baseline to 10% at 3 years. The BMD declined after 9 months treatment, at -1.9% and -3.3% at hip and spine, respectively (P < 0.001). Subsequent BMD decline in the POST period was attenuated; at 1 years and 2 years later, hip -0.6% (not significant), and -0.8% (P < 0.014), and spine +1.0% and +0.2% (not significant). The BMD change in those remaining 'off' therapy for 2 years (n = 20) was strongly associated with the level of testosterone recovery; a peak testosterone level of <5 nmol/L associated with a greater then normal physiological loss. Testosterone recovery was less likely in older men.. The attenuation of spine and hip BMD decline after 3-year IAST compared with those reported for continuous AST appears to be due to testosterone driven BMD recovery in the POST period. Failure of testosterone recovery was associated with worse final BMD. By reducing the potential risk for adverse bone complications, intermittent therapy may become an important consideration when the therapeutic ratio is narrow.

Topics: Adult; Aged; Aged, 80 and over; Androgen Antagonists; Antineoplastic Combined Chemotherapy Protocols; Bone Density; Cohort Studies; Flutamide; Hip; Humans; Leuprolide; Male; Middle Aged; Osteoporosis; Prostatic Neoplasms; Quality of Health Care; Spine; Testosterone; Time Factors

To assess the feasibility and tolerability of intermittent androgen suppression therapy (IAS) in prostate cancer.. Patients with recurrent or metastic prostate cancer received cyclical periods of treatment with leuprolide acetate and nilutamide for 8 months, and rest periods. Cycles were repeated at progression until the treatment failed to achieve normal prostate-specific antigen (PSA) levels. Patients were followed with PSA level, testosterone level, haemoglobin level, weight and bone mineral density evaluations. The median time to treatment failure, recovery from anaemia, or normalization of testosterone level was estimated by the Kaplan-Meier method.. In all, 95 patients received 245 cycles; the median duration of rest periods was 8 months and median time to treatment failure 47 months. Testosterone recovery during rest periods was documented in 117 (61%) of cycles. Anaemia was mild and reported in 33%, 44% and 67% of cycles 1, 2 and 3, respectively. Sexual function recovered during the rest periods in 47% of cycles. There was no significant overall change in body mass index at the end of the treatment period. Osteoporosis was documented in at least one site evaluated in 41 patients (37%).. IAS has the potential to reduce side-effects, including recovery of haemoglobin level, return of sexual function and absence of weight gain at the end of the study period.

Topics: Aged; Aged, 80 and over; Androgen Antagonists; Antineoplastic Agents; Disease-Free Survival; Follow-Up Studies; Humans; Imidazolidines; Leuprolide; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Recurrence, Local; Osteoporosis; Prostate-Specific Antigen; Prostatic Neoplasms; Testosterone; Treatment Outcome

To determine if there is an age-related effect on bone mineral density (BMD) loss with GnRH agonist treatment of endometriosis and, in particular, whether the impact of this therapy in terms of BMD loss is different if it is used at an age prior to attainment of peak BMD than after attaining it.. Data from a randomized, double-placebo-controlled clinical trial comparing efficacy and safety of two GnRH agonists, without add-back, for the treatment of endometriosis, were analyzed.. No significant age-related effect was detected for either GnRH agonist on absolute BMD loss with a single, six-month course. However, in women at an age prior to peak BMD, prevention of the natural increase in BMD with these drugs may prevent women from attaining their peak BMD and thus increase their risk of osteoporosis in later life.. GnRH agonists should be used with caution and perhaps only with strategies designed to minimize the impact on BMD in women prior to attainment of peak BMD.

Topics: Absorptiometry, Photon; Adolescent; Adult; Age Factors; Aged; Bone Density; Double-Blind Method; Endometriosis; Female; Gonadotropin-Releasing Hormone; Humans; Leuprolide; Middle Aged; Nafarelin; Osteoporosis; Randomized Controlled Trials as Topic

This prospective randomized, single-blind, placebo-controlled clinical trial was performed to evaluate the efficacy of raloxifene in preventing the bone loss associated with GnRH agonist (GnRH-a) administration. One hundred premenopausal women with uterine leiomyomas were treated with leuprolide acetate depot at a dosage of 3.75 mg/d for 28 d and then randomized into two groups to receive raloxifene hydrochloride at 60 mg/d (group A) or placebo (1 tablet/d; group B). Bone mineral density (BMD) and serum bone metabolism markers were evaluated at admission and after six treatment cycles. Posttreatment BMD differed significantly from baseline BMD in group B but not in group A. BMD was significantly higher in group A than in group B. In group A, serum osteocalcin and bone alkaline phosphatase levels and urinary deoxypyridinoline and pyrilinks-D excretion were unchanged vs. baseline. Differently, posttreatment concentrations of these bone turnover markers were significantly lower in group B compared with baseline and group A values. In conclusion, raloxifene prevents GnRH-a related bone loss in premenopausal women with uterine leiomyomas.

Topics: Adult; Body Mass Index; Bone and Bones; Bone Density; Calcium; Delayed-Action Preparations; Female; Femur; Humans; Leiomyoma; Leuprolide; Lumbar Vertebrae; Middle Aged; Osteoporosis; Phosphorus; Placebos; Premenopause; Prospective Studies; Raloxifene Hydrochloride; Selective Estrogen Receptor Modulators; Uterine Neoplasms

The purpose of this study was to evaluate the efficacy of ipriflavone in preventing bone loss, decreasing in serum cholesterol and decreasing the rate of appearance of vasomotor symptoms, as well as the effects of ipriflavone on reduction of myoma volume by estrogen deficiency during treatment with the GnRH analog leuprolide. One hundred two women (mean age, 44.3 +/- 0.53 yr) receiving leuprolide therapy for uterine leiomyoma were randomly allocated to two groups (group A, leuprolide only; group B, leuprolide with ipriflavone). Bone mineral density of the lumbar spine was measured by dual-energy x-ray absorptiometry before and after treatment for 6 months. Levels of serum total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol (LDL-C) were measured before treatment and after 3 and 6 months of treatment. Subjects were asked to report the appearance of vasomotor symptoms throughout treatment. Myoma node volumes were measured before treatment and after treatment for 6 months. Bone mineral density was reduced in both groups, with reduction rates of -5.26% in group A and -3.70% in group B (P < 0.01 vs. group A). Changes in bone markers were not significant in either group. TC was significantly increased in both groups, and TG levels were increased significantly after 3 and 6 months of treatment in group A but not in group B. There was no significant difference between these two groups in amount of increase of either TC or TG. LDL-C levels were increased significantly after 3 and 6 months of treatment in both groups, and the differences between the groups (11.7% in group A vs. 7.5% in group B at 3 month and 22.6% in group A vs. 8.4% in group B at 6 month) were significant. Severe vasomotor symptoms were reduced in group B. The rates of reduction of myoma volume were 49.8% in group A and 52.9% in group B; this difference between groups was not significant. Ipriflavone efficaciously alleviated the adverse effects of estrogen deficiency such as bone loss and increase in LDL-C level, and the ability of leuprolide therapy to reduce myoma volume was not decreased by ipriflavone administration.

Topics: Adult; Bone Density; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Estrogen Antagonists; Female; Humans; Isoflavones; Leiomyoma; Leuprolide; Middle Aged; Osteoporosis; Triglycerides; Uterine Neoplasms

Treatment with a gonadotropin-releasing hormone agonist decreases bone mineral density and increases the risk of fracture in men with prostate cancer. We conducted a controlled study of the prevention of osteoporosis in men undergoing treatment with a gonadotropin-releasing hormone agonist.. In a 48-week, open-label study, we randomly assigned 47 men with advanced or recurrent prostate cancer and no bone metastases to receive either leuprolide alone or leuprolide and pamidronate (60 mg intravenously every 12 weeks). Bone mineral density of the lumbar spine and the proximal femur was measured by dual-energy x-ray absorptiometry. Trabecular bone mineral density of the lumbar spine was measured by quantitative computed tomography. Forty-one men completed the study.. In men treated with leuprolide alone, the mean (+/-SE) bone mineral density decreased by 3.3+/-0.7 percent in the lumbar spine, 2.1+/-0.6 percent in the trochanter, and 1.8+/-0.4 percent in the total hip, and the mean trabecular bone mineral density of the lumbar spine decreased by 8.5+/-1.8 percent (P<0.001 for each comparison with the base-line value). In contrast, the mean bone mineral density did not change significantly at any skeletal site in men treated with both leuprolide and pamidronate. There were significant differences between the two groups in the mean changes in bone mineral density at 48 weeks in the lumbar spine (P<0.001), trochanter (P = 0.003), total hip (P=0.005), and trabecular bone of the lumbar spine (P=0.02).. Pamidronate prevents bone loss in the hip and lumbar spine in men receiving treatment for prostate cancer with a gonadotropin-releasing hormone agonist.

Topics: Aged; Antineoplastic Agents, Hormonal; Bone Density; Bone Resorption; Diphosphonates; Femur; Gonadotropin-Releasing Hormone; Humans; Leuprolide; Lumbar Vertebrae; Male; Osteocalcin; Osteoporosis; Pamidronate; Pelvic Bones; Prostatic Neoplasms

The hypoestrogenic state induced by gonadotropin-releasing hormone agonists (GnRHa) has been shown to be effective in the treatment of uterine leiomyomas but to induce bone loss. Estriol has been described to be a weak and short-acting estrogen without an increased risk of endometrial proliferation and hyperplasia. The purpose of this study was to evaluate whether treatment of uterine leiomyomata with GnRHa plus oral estriol add-back therapy could prevent bone loss, without deteriorating the therapeutic effect of GnRHa. Twelve premenopausal women with symptomatic uterine leiomyomas were randomized to receive either leuprolide acetate depot alone at a dose of 3.75 mg s.c. every month for 6 months (non add-back group; n = 6), or GnRHa for 6 months plus oral estriol 4 mg/day for 4 months commencing with the third GnRHa injection (add-back group; n = 6). In the add-back group, leiomyoma volume, as measured by transvaginal ultrasound, decreased to 59.1% of baseline at 2 months of GnRHa therapy with no significant change in size during the remaining treatment period. In contrast, it decreased to 31.3% of pretreatment size at the end of treatment in the non add-back group. The levels of bone metabolic markers such as CrossLaps, deoxypyridinoline, osteocalcin and bone-specific alkaline phosphatase, increased significantly throughout the treatment in the non add-back group, whereas they were suppressed by the add-back therapy. The bone mineral density of lumbar spine (L2-L4) as measured by dual-energy X-ray absorptiometry decreased significantly by 7.5% at the end of treatment in the non add-back group, but did not change significantly in the add-back group. In conclusion, GnRHa plus estriol add-back therapy might be considered for long-term treatment of uterine leiomyomata.

Topics: Absorptiometry, Photon; Adult; Antineoplastic Agents, Hormonal; Bone Density; Delayed-Action Preparations; Estriol; Female; Humans; Leiomyoma; Leuprolide; Lumbar Vertebrae; Middle Aged; Osteoporosis; Uterine Neoplasms

The aim of this study is to evaluate the association between GnRH analogues and ipriflavone, drug modulating the bone turnover limiting the negative bone effects of analogue. Thirty patients (33 +/- 5.4 years, mean +/- SD) affect by benign gynecological conditions in which there was an indication to use GnRH analogs have been treated with leuprolide acetate at the monthly intramuscular dose of 3.75 mg, for six months. Fifteen of these patients also received 600 mg/day per os of ipriflavone (group A), while the other 15 patients have been treated exclusively with leuprolide acetate (group B). Before and after treatment, radial bone mineral density (BMD) and main markers of bone turnover were measured in all patients. Before treatment no difference in the considered parameters could be detected between the two groups. In group A, after 6 months of treatment no significant decrease in BMD and no variations in the bone turnover parameters. On the contrary, in group B, after six months of treatment, a significant decrease (p < 0.05) in BMD was observed in comparison to basal and group A values. In the same group alkaline phosphatase, osteocalcin and urinary calcium/creatinine and hydroxyproline/creatinine ratio proved significantly increased in comparison to basal and group A values (both with p < 0.05). Ipriflavone, therefore, seems to be effective in counteracting the negative effects of GnRH-a induced on bone.

Topics: Analgesics; Antineoplastic Agents, Hormonal; Bone Remodeling; Female; Genital Diseases, Female; Genital Neoplasms, Female; Humans; Isoflavones; Leuprolide; Osteoporosis; Time Factors

To determine changes in trabecular vertebral bone mass, serum E2, and serum calcitonin during and after therapy of pelvic endometriosis with depot leuprolide acetate (LA) or danazol.. Prospective, randomized, double-blind study.. Academic university hospital and department of obstetrics and gynecology.. Twelve women with symptomatic pelvic endometriosis diagnosed and staged by laparoscopy.. All patients received blinded treatment with either 3.75 mg JM depot LA given every month and daily placebo tablets (n = 6) or 800 mg oral danazol daily with a monthly placebo injection (n = 6) for 24 weeks.. Quantitated computerized tomography of bone density of thoracic 12 to lumbar 4 vertebral bodies were determined before, at the end of 24 weeks of treatment, and 6 and 12 months after completing treatment. Gain or loss of bone mass was based against pretreatment levels. Serial serum levels of E2 and calcitonin before, throughout, and after therapy were compared with changes in bone mass.. Bone loss with LA was 14.0% +/- 0.5% (mean +/- SEM), recovering to a deficit of 4.2% +/- 3.8% and 3.3%, 6 and 12 months after stopping therapy. Danazol increased bone by 5.4% +/- 2.2%, with a further gain to 8.2% +/- 3.5% and 7.5%, 6 and 12 months after stopping treatment. Serum E2 levels usually were < 25 pg/mL (conversion factor to SI unit, 3.671) with LA but > 47.3 pg/mL with danazol. Calcitonin levels did not change significantly with either treatment.. Depot LA produced marked sustained hypoestrogenemia and significant bone loss with incomplete recovery 1 year after stopping treatment. Danazol maintained normoestrogenemia and increased bone mass with the gain maintained even 1 year after stopping therapy.

Topics: Adult; Bone Density; Calcitonin; Danazol; Delayed-Action Preparations; Double-Blind Method; Endometriosis; Estradiol; Female; Humans; Leuprolide; Osteoporosis; Phosphates; Potassium Compounds; Prospective Studies; Spine

Osteoporosis is detrimental to the health of skeletal structure and significantly increases the risks of bone fracture. Moreover, bone regeneration is adversely impaired by increased osteoclastic activities as a result of osteoporosis. In this study, we developed a novel formulation of injectable bone cement based on calcium phosphate silicate cement (CPSC) and leuprolide acetate (LA). Several combinations of LA-CPSC bone cement were characterized and, it is found that LA could increase the setting time and compressive strength of CPSC in a concentration-dependent manner. Moreover, the

Topics: Animals; Bone Cements; Bone Regeneration; Calcium Phosphates; Female; Leuprolide; Osteoclasts; Osteoporosis; Rats; Rats, Sprague-Dawley; Silicate Cement

Paraphilia is a complex psychological and psychiatric disorder that has been difficult to treat. Leuprorelin has been used as one of the therapeutic methods for paraphilia. Leuprorelin administration could change insulin resistance and accelerate bone loss. The case study in this work was a 59-year-old man who visited a hospital with the chief complaints of frotteuristic behaviors in public places, a continuous increase in sexual desire, and sexual molestation behavior that started in 2007. We injected leuprorelin (3.6 mg) intramuscularly every month for this patient with paraphilia and comorbidities of osteoporosis and hyperthyroidism. The clinical global impression (CGI), Sex Addiction Screening Test (SAST), Wilson Sex Fantasy Questionnaire (WSFQ), physical examination, and laboratory tests were performed. After 12 months of leuprorelin injection for paraphilia, we found a significant improvement in abnormal sexual behavior/desire without aggravation of osteoporosis/hyperthyroidism. Gonadotrophin-Releasing Hormone (GnRH) analogs could be used as alternative or supplementary treatment methods for paraphilia with osteoporosis/hyperthyroidism.

Topics: Delayed-Action Preparations; Humans; Leuprolide; Male; Middle Aged; Osteoporosis; Paraphilic Disorders

To determine the effect of leuprolide acetate, a synthetic gonadotropin-releasing hormone analog (GnRH-a) on ovarian function preservation in systemic lupus erythematosus (SLE) patients treated with cyclophosphamide (CYC) in clinical practice.. We enrolled 30 premenopausal female SLE patients who fulfilled the 1997 American College of Rheumatology revised criteria and were treated with intravenous CYC (IVCY) in 2008-2017. We used Kaplan-Meier survival estimates to compare the GnRH-a-treated patients and those not treated with GnRH-a as controls. We performed Cox regression analyses to identify factors associated with premature ovarian failure (POF), incidences of cardiovascular events, strokes and osteoporosis after IVCY therapy.. After a mean follow-up of 41 months, POF developed in one of the 16 GnRH-a-treated patients (6%) versus seven of the 14 controls (50%). Significantly improved cumulative ovarian protection over time was observed in the GnRH-a-treated group (P = 0.030). The hazard model analysis showed that treatment with GnRH-a during IVCY therapy is an independent factor associated with POF after IVCY therapy (adjusted hazards ratio = 0.12, 95% CI 0.01-0.67, P = 0.013) but not incidences of cardiovascular events, strokes or osteoporosis.. The combined use of GnRH-a with IVCY therapy was associated with a significant reduction of POF among premenopausal women with SLE, suggesting that the addition of GnRH-a can be a strategy to prevent POF among premenopausal women with SLE after IVCY therapy.

Topics: Administration, Intravenous; Adult; Cardiovascular Diseases; Case-Control Studies; Cyclophosphamide; Female; Fertility Agents, Female; Fertility Preservation; Humans; Immunosuppressive Agents; Incidence; Infertility, Female; Kaplan-Meier Estimate; Leuprolide; Lupus Erythematosus, Systemic; Multivariate Analysis; Osteoporosis; Ovary; Premenopause; Primary Ovarian Insufficiency; Proportional Hazards Models; Stroke; Time Factors; Treatment Outcome; Young Adult

The aim of this study was to evaluate bone mass changes after 1 year of four different types of pharmacological intervention. Ninety-seven prostate cancer patients treated with androgen deprivation therapy, and severe osteopenia or osteoporosis were retrospectively studied. Patients were divided in four groups. Group 1: 28 patients treated with denosumab, Group 2: 24 patients treated with alendronate, Group 3: 24 patients with no antiresorptive treatment and Group 4: 21 patients previously treated with alendronate and switched to denosumab. Dual X-ray absorptiometry was performed at baseline and after 1 year. Bone mass changes at the L2-L4 lumbar spine, femoral neck and total hip were evaluated. No differences were found at baseline. After 1 year, men receiving denosumab or alendronate (Group 1 and 2) showed a significant bone mass increase at the lumbar spine (+2.4 and +5.0 %, respectively), while no significant changes were observed in Group 3 and 4. At the femoral neck, Group 1 and 2 patients showed a significant bone mass increase (+3.7 and +3.6 %, respectively), while no significant changes were observed in Group 3 and 4. At the total hip, we observed a significant bone mass increase in Group 1 (+2.9 %) and a significant bone mass loss in Group 3 patients (-1.9 %). No significant changes were observed in Group 2 and 4. Denosumab increased significantly bone mass in all three dual X-ray absorptiometry standard sites, while alendronate did not at total hip. No benefit was observed in men previously treated with alendronate who switched to denosumab treatment.

Topics: Aged; Aged, 80 and over; Alendronate; Androgen Antagonists; Anilides; Antibodies, Monoclonal, Humanized; Bone Density Conservation Agents; Bone Diseases, Metabolic; Denosumab; Femur Neck; Humans; Leuprolide; Lumbar Vertebrae; Male; Nitriles; Osteoporosis; Prostatic Neoplasms; Radiography; Tosyl Compounds

Patients receiving androgen deprivation therapy undergo a rapid decline in bone mineral density during the first 6 to 12 months of initiating therapy. The World Health Organization has developed and implemented the Fracture Risk Assessment Tool (FRAX) to predict the ten year risk of a major fracture & hip fracture. Additionally, the National Comprehensive Cancer Network and the National Osteoporosis Foundation have developed osteoporosis guidelines. This study aims to characterize the fracture risk (based on the FRAX tool) and the current management of bone health based on national guidelines compliance.. A retrospective chart review of patients receiving a LHRH agonist at our institution was conducted. Data collection commenced upon Institutional Review Board approval and included demographics, past medical history, medication regimen, history of androgen deprivation therapy, bone health and its management. The ten year fracture risk calculated with the collected information using the FRAX tool.. A total of 174 subjects included with a mean age of 65.5 years, 71.8% had stage II prostate cancer, 97.7% received the LHRH agonist leuprolide for a mean of 13.8 ± 18.1 months. In addition to ADT, 57% of patients had ≥ 2 risk factors for developing osteoporosis. The risk of sustaining a major fracture increased from 4% to 5.6% after the initiation of ADT (P = <0.001). The risk for sustaining a hip fracture rose from 1.3% to 2.2% (P = <0.001). National guideline compliance was found to be 9%, 5% and 3% respectively for obtaining Dual Energy X-ray Absorptiometry (DEXA) scans, calcium supplementation, and vitamin D supplementation.. In addition to predisposing risk factors for osteoporosis, ADT significantly increases the fracture risk in the prostate cancer population. There is room for improvement in the management of bone health as some intervention could have been made in over 90% of patients evaluated.

Topics: Absorptiometry, Photon; Aged; Aged, 80 and over; Androgen Antagonists; Antineoplastic Agents, Hormonal; Bone Density; Calcium; Fractures, Bone; Gonadotropin-Releasing Hormone; Guideline Adherence; Humans; Leuprolide; Male; Middle Aged; Osteoporosis; Practice Guidelines as Topic; Prostatic Neoplasms; Retrospective Studies; Risk Factors; Vitamin D

To identify whether veterans receiving androgen-deprivation therapy (ADT) are screened at any time by bone mass measurement.. Cross-sectional study.. Veterans Administration Tennessee Valley Healthcare System (VA-TVHS).. All male veterans who received at least one dose of goserelin or leuprolide within the fiscal years October 1, 2005, through September 30, 2009.. Data from patients' charts were extracted for demographic information (race, age, and weight prior to the initial injection); date of initiation of therapy; the use of calcium, vitamin D, bisphosphonate, or calcitonin therapy; and documented bone-mineral density testing.. To determine whether veterans receiving ADT with goserelin or leuprolide for prostate cancer were screened at any time for BMD more or less than rates as documented in previous literature.. 22.8% of veterans were screened for BMD, which was statistically significant when compared with results found in previous literature.. Although rates of BMD testing were higher at VA-TVHS compared with previous literature, this rate is still low given the well-known risk of accelerated osteoporosis associated with ADT.

Topics: Aged; Androgen Antagonists; Androgens; Antineoplastic Agents, Hormonal; Bone Density; Cross-Sectional Studies; Goserelin; Humans; Leuprolide; Male; Osteoporosis; Prostatic Neoplasms; Risk Assessment; Veterans

Topics: Adenocarcinoma; Androgen Antagonists; Antineoplastic Agents, Hormonal; Biopsy; Bone Neoplasms; Chemotherapy, Adjuvant; Humans; Leuprolide; Male; Middle Aged; Neoplasm Recurrence, Local; Osteoporosis; Prostate; Prostate-Specific Antigen; Prostatectomy; Prostatic Neoplasms

Topics: Adult; Antineoplastic Agents; Antineoplastic Agents, Hormonal; Bone Density; Female; Flutamide; Humans; Leuprolide; Male; Middle Aged; Neoplasm Staging; Neoplasms; Osteoporosis; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prostatic Neoplasms; Survivors

Our objective was to assess the effects of 6 months' treatment with two types of gonadotropin-releasing hormone (GnRH) analogues on lumbar bone mineral density (BMD) and bone metabolism. We studied 27 women who had been given a diagnosis of endometriosis or uterine myoma. The subjects received drug therapy for 6 months and were subsequently followed up for 1 year. The BMD of the lumbar spine (L2, L3, L4) was measured by dual energy X-ray absorptiometry four times: at baseline, after 6 months, after 12 months, and after 18 months. The serum concentrations of sex steroids and bone metabolic markers were measured at the same times as BMD. Compared with the baseline value, the mean decrease in the buserelin group L2-4 BMD was 3.7% at 6 months, 1.7% at 12 months, and 0.4% at 18 months. In the leuprolide group, L2-4 BMD decreased respectively by 5.1%, 6.2%, and 4.3%. Serum concentrations of calcium increased significantly after 6 months of treatment (P < 0.05) and returned to the baseline level at 12 months in both groups. In the leuprolide group, the intact osteocalcin concentration after 6 months was significantly higher than the baseline value, and after 12 months, it decreased to the baseline level. Our results indicate that the effect on BMD of 6 months' treatment with GnRH analogues virtually resolves by 1 year after treatment, provided that drugs affecting bone metabolism are not given during this period.

Topics: Absorptiometry, Photon; Adult; Bone and Bones; Bone Density; Buserelin; Endometriosis; Female; Gonadotropin-Releasing Hormone; Humans; Japan; Leuprolide; Lumbar Vertebrae; Osteocalcin; Osteoporosis; Time Factors; Uterus

To better understand bone metabolism and predict bone loss in treatment using gonadotropin-releasing hormone agonist for patients with prostate cancer.. The changes in bone mineral density and blood levels of bone metabolism markers and the level of pyridinoline cross-linked carboxy-terminal telopeptide of type I collagen, a specific marker of bone resorption, and carboxy-terminal pro-peptide of human type I procollagen, a specific marker of bone formation, were examined in 27 consecutive patients with prostate cancer without bone metastasis.. After 2 years of gonadotropin-releasing hormone treatment, the bone mineral density was significantly lower (median 0.937 g/cm2) than before treatment. Pyridinoline cross-linked carboxy-terminal telopeptide of type I collagen began to increase significantly 6 months after the start of treatment (3.0 to 8.3 ng/mL, median 4.6, at baseline versus 3.4 to 8.2 ng/mL, median 5.2, after 6 months). Carboxy-terminal pro-peptide of human type I procollagen began to show a significant rise 1 year after the start of treatment (from 72.8 to 221.5 ng/mL, median 102.0, at baseline to 82.7 to 293.4 ng/mL, median 132.0, at 1 year).. Functional coupling between bone resorption and formation was noted, and a decrease in bone mass, even in men, owing to androgen deficiency, was biochemically demonstrated. Fluctuations in these two bone metabolism markers preceded the decrease of bone mineral density. Therefore, these markers might be a predictor of bone loss.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Biomarkers; Bone and Bones; Bone Density; Bone Remodeling; Bone Resorption; Collagen Type I; Gonadotropin-Releasing Hormone; Goserelin; Humans; Leuprolide; Male; Middle Aged; Osteoporosis; Peptide Fragments; Peptides; Procollagen; Prostatic Neoplasms; Testosterone

Osteoporosis and long-term androgen suppression in the treatment of paraphilias has been documented with surgical castration and the use of gonadotropin-releasing hormone agonists. The literature has suggested that the use of cyproterone acetate (CPA) may be protective against osteoporosis, although there are case reports of osteoporosis in men treated with CPA. This pilot study represents a case series of seven patients diagnosed with severe paraphilias and treated with CPA, leuprolide, or surgical castration. Two of the four patients treated with CPA developed significant osteoporosis, while the other two had normal bone density studies. The remaining three patients, one treated with leuprolide and two with surgical castration, had osteopenia. Based upon the current literature, the finding of significant osteoporosis in two of four patients treated with CPA, but not those treated with leuprolide or castration, is surprising. Monitoring of all patients treated with long-term androgen suppression for osteoporosis is suggested.

Topics: Adult; Androgen Antagonists; Bone Density; Cyproterone Acetate; Forensic Psychiatry; Humans; Leuprolide; Male; Middle Aged; Osteoporosis; Paraphilic Disorders; Pilot Projects

The objective of this work was to determine the effect of androgen deprivation therapy (ADT) on rates of bone mineral density (BMD) loss in men with prostate cancer. It was a prospective study comparing men receiving ADT to age matched controls for 2 y. Subjects received a history, physical exam, bone mineral density measurement, and laboratory evaluation every 6 months. Thirty-nine subjects receiving continuous ADT for prostate cancer (subjects) were compared to 39 age-matched controls not receiving ADT (controls). Twenty-three subjects and 30 controls completed the study through 24 months. Men in the ADT group demonstrated greater rates of bone mineral density loss than men in the control group at every site except the lumbar spine. Twenty-four month per cent of bone mineral density loss is presented as mean+/-standard error (s.e.). At the distal forearm, the ADT group value was -9.4%+/-1.0% and -4.4%+/-0.3% for controls (P<0.0005). The ADT group femoral neck values were -1.9%+/-0.7% and 0.6%+/-0.5% in the control group (P=0.0016). The ADT group total hip value was -1.5%+/-1.0% and 0.8%+/-0.5% in the control group (P=0.0018). The ADT group trochanter value was -2.0%+/-1.3% and -0.1%+/-0.5% in the control group (P=0.0019). The ADT group lumbar spine value was -0.2%+/-0.8 % and 1.1%+/-0.6% in the control group (P=0.079). Our data demonstrate greater rates of bone mineral density loss in men receiving androgen deprivation therapy for prostate cancer.

Topics: Absorptiometry, Photon; Adenocarcinoma; Aged; Amino Acids; Androgen Antagonists; Androgens; Anilides; Antineoplastic Agents, Hormonal; Biomarkers; Bone Density; Bone Remodeling; Calcium; Drug Therapy, Combination; Flutamide; Gonadotropin-Releasing Hormone; Goserelin; Humans; Leuprolide; Male; Neoplasms, Hormone-Dependent; Nitriles; Orchiectomy; Osteoporosis; Prospective Studies; Prostatic Neoplasms; Testosterone; Tosyl Compounds

We characterize the consequences of androgen deprivation therapy on body composition in elderly men.. Using a dual energy x-ray absorptiometry instrument, we determined the changes in bone mineral density, bone mineral content, fat body mass and lean body mass in 35 patients with prostate cancer without bone metastases who received luteinizing hormone releasing hormone analogue for 12 months.. At baseline conditions 46% of cases were classified as osteopenic and 14% as osteoporotic at the lumbar spine and 40% were osteopenic and 4% osteoporotic at the hip. Androgen deprivation significantly decreased bone mineral density either at the lumbar spine (mean gm./cm.2 [SD] 1.00 [0.194], 0.986 [0.172] and 0.977 [0.182] at baseline, and 6 and 12 months, respectively, p <0.002) or the hip (0.929 [0.136], 0.926 [0.144] and 0.923 [0.138], p <0.03). A more than 2% decrease in bone mineral density was found at the lumbar spine in 19 men (54.3%) and at the hip in 15 (42.9%). Bone mineral content paralleled the bone mineral density pattern. Lean body mass decreased (mean gm. [SD] 50,287 [6,656], 49,296 [6,554] and 49,327 [6,345], p <0.003), whereas fat body mass consistently increased (18,115 [6,209], 20,724 [6,029] and 21,604 [5,923] p <0.001).. Serial bone densitometry evaluation during androgen deprivation therapy may allow the detection of patients with prostate cancer at risk for osteoporotic fractures, that is those with osteopenia or osteoporosis at baseline and fast bone loss. The change in body composition may predispose patients to accidental falls, thus increasing the risk of bone fracture.

Topics: Absorptiometry, Photon; Adipose Tissue; Aged; Aged, 80 and over; Androgen Antagonists; Antineoplastic Agents, Hormonal; Body Composition; Body Mass Index; Bone Density; Bone Diseases, Metabolic; Flutamide; Hip Joint; Humans; Leuprolide; Lumbar Vertebrae; Male; Middle Aged; Osteoporosis; Prostatic Neoplasms; Thinness

Topics: Administration, Inhalation; Antineoplastic Agents, Hormonal; Bone Density; Bone Resorption; Diphosphonates; Female; Glucocorticoids; Gonadotropin-Releasing Hormone; Humans; Leuprolide; Male; Osteoporosis; Pamidronate; Prostatic Neoplasms; Triamcinolone Acetonide

Luteinizing hormone-releasing hormone (LHRH) agonists are popularly used drugs in the treatment of prostatic cancer. However, it has been reported that continuation of a low testosterone level following a longterm administration of these drugs reduces the bone mineral density and makes for osteoporosis, which is accountable for fracture, we measured the bone mineral density and bone metabolic markers in the cases who suffered fracture receiving LHRH agonists for prostatic cancer.. Between 1994 and 1998, 196 patients (mean age 78.1 years) were treated with LHRH agonists for prostatic cancer. Of these patients, 13(7%) who had bone fracture during treated with LHRH agonists were divided into fracture group, and 70 patients who had not bone fracture divided into non-fracture group. Fracture by traffic accident was excluded. The bone density in the third lumbar vertebra was measured using quantitative computed tomography (QCT). Osteocalcin, 1, 25- (OH)2 vitamin D, urinary type 1 collagen cross-linked N-telopeptides (NTx), parathyroid hormone (PTH) and calcitonin were measured as bone metabolic markers.. The mean age of fractured cases was 78 years. The period from the start of treatment to fracture was 11 to 45 months (mean 27 months). No case of fracture at the site of metastasis of prostatic cancer was found. The bone density was significantly low in the fracture group compared with that of non-fracture group. Of the bone metabolic markers, NTx showed high values in the fracture group.. There is a need to measure bone mineral density and bone metabolic markers periodically and to evaluate secondary osteoporosis in the patients receiving LHRH agonists for prostatic cancer.

Topics: Aged; Aged, 80 and over; Antineoplastic Agents, Hormonal; Bone Density; Fractures, Bone; Gonadotropin-Releasing Hormone; Goserelin; Humans; Leuprolide; Male; Osteoporosis; Prostatic Neoplasms; Spine

It is well known that androgens play an important role in bone metabolism and male hypogonadism induce osteoporosis. Luteinizing hormone-releasing hormone analogue (LHRH-a) which is essential for conservative therapy of prostatic carcinoma (CaP) ultimately reduces circulating testosterone to castration levels. The purpose of this study was to determine the risk of decrease of bone mineral density in men receiving LHRH-a for CaP.. Fifty-three man with CaP aged 63 to 95 years (mean 75.5 years) were included in this study. Seven patients received LHRH-a with estrogen drug, forty-six patients received LHRH-a with or without anti androgen drug. To estimate patient's bone density we use the second metacarpal bone density using a microdensitometry method.. Blood level of sex hormone of the forty-six patients who were received LHRH-a without estrogen, was the same as that of castration. Patients who were treated more than twelve months had less bone density than patients who were treated less than eleven months. As the duration of medical castration period was prolonged, patients bone density were reduced. Whereas seven patients who received estrogen drug did not find a decrease of bone density regardless of duration of treatment period.. Hypogonadism induced LHRH-a also reduce bone density, so there is a risk of iatrogenic osteoporosis caused by therapy for CaP with LHRH-a. Patients with osteoporosis easily suffer from a much complicated and pernicious bone fracture, so we should measure bone density of male patients same as female treated with LHRH-a for a long-term.

Topics: Aged; Aged, 80 and over; Antineoplastic Agents, Hormonal; Bone Density; Estrogens; Gonadotropin-Releasing Hormone; Goserelin; Humans; Leuprolide; Male; Middle Aged; Osteoporosis; Prostatic Neoplasms; Risk

Topics: Aged; Alendronate; Animals; Antineoplastic Agents, Hormonal; Diphosphonates; Humans; Leuprolide; Male; Orchiectomy; Osteoporosis; Prostatic Neoplasms; Rats

Therapy of endometriosis with a GnRH-agonist (Leuprorelin) demonstrated a good therapeutical efficiency. As a side effect it had a significant negative impact on trabecular bone mass (non significant on cortical bone) as measured by DXA. Rising levels of Osteocalcin indicated the stimulation of bone remodelling. Three years after the end of the therapy a long term follow up control was able to detect the complete recovery of the mean density values in the extremities with even higher values in some patients compared with the initial measurement. In the spine half of the patients reached or surpassed the initial values. Regarding the patients history the differences in the recovery were obviously due to a different lifestyle especially body exercise, and not due to a different reaction to the GnRH-agonist therapy. Without being able to predict the individual bone loss due to a GnRH agonist therapy the results of this study indicate that the transient oestrogen deficiency does not result in a relevant long term bone loss or an elevated risk of osteoporosis. On the other hand in case of known risk factors or of a prolonged or repeated GnRH-agonist therapy the individual bone density and the individual bone loss should be controlled by DXA. Those patients with a significant negative impact on their bone mass then can be treated directly.

Topics: Adolescent; Adult; Antineoplastic Agents, Hormonal; Bone Density; Bone Remodeling; Delayed-Action Preparations; Endometriosis; Female; Follow-Up Studies; Humans; Leuprolide; Long-Term Care; Osteocalcin; Osteoporosis

This study was carried out (1) to compare the time-course of the change in bone metabolism in rats administered gonadotrophin-releasing hormone agonist (GnRHa) and bilaterally ovariectomized (OVX) rats and (2) to investigate the changes in bone metabolism after discontinuance of GnRHa. Seventy female Sprague-Dawley rats, aged 90 days, were divided into four groups. Group 1 underwent a sham operation, group 2 was surgically ovariectomized and group 3 was given a GnRHa (leuprorelin acetate for depot suspension) s.c. injection every 30 days. Group 3 was further divided into three subgroups: rats were administered GnRHa for 12 months (GnRHa 12M), 6 months (GnRHa 6M) or 3 months (GnRHa 3M). Group 4 served as a basal control. The bone mineral density (BMD) of lumbar vertebrae and femoral bone, measured by dual-energy X-ray absorptiometry, and the serum bone metabolic parameters were determined every 45-90 days. The bone histomorphometry of lumbar vertebra was measured on days 180 and 360 after surgery. GnRHa 12M rats showed significantly lower BMD of vertebrae and femoral bone, lower bone volume and higher bone turnover compared with sham-operated rats and those with secondary hyperparathyroidism on days 180 and 360. Their time-course for changes in bone metabolism was almost the same as that of OVX rats. GnRHa-discontinued rats showed a recovery of bone turnover. The recovery of BMD in GnRHa 6M rats was smaller than that of GnRHa 3M rats after GnRHa discontinuance. The bone volume for GnRHa 6M rats was significantly lower than that for GnRHa 3M on day 360.

Topics: Absorptiometry, Photon; Animals; Bone Density; Calcium; Dose-Response Relationship, Drug; Estradiol; Female; Femur; Gonadotropin-Releasing Hormone; Hyperparathyroidism; Leuprolide; Lumbar Vertebrae; Luteinizing Hormone; Osteoporosis; Ovariectomy; Rats; Rats, Sprague-Dawley; Time Factors