Goserelin Therapy Research Articles

Efficacy and uterine bleeding patterns in initiating goserelin therapy during different menstrual phases in patients with adenomyosis: a prospective cohortstudy.

We carried out this study to explore the possibility of initiating goserelin therapy during the non-menstrual period in patients diagnosed with adenomyosis. 115 premenopausal adenomyosis patients were enrolled and divided into three groups based on their menstrual cycle phase during the initial outpatient visit: menstrual, follicular, and luteal. Each received a 3.6 mg subcutaneous dose of goserelin monthly for three months. The endpoints encompassed alterations in uterine volume, dysmenorrhea Numerical Rating Scale (NRS) score, CA125 level, hemoglobin (HGB) after a 12-week treatment course, and the occurrence and duration of uterine hemorrhage during the first treatment cycle. Analysis revealed that the timing of goserelin therapy initiation in the menstrual cycle did not significantly impact its effectiveness in reducing uterine size, alleviating pain, lowering CA125 levels, or improving hemoglobin concentrations. However, patients starting treatment during the luteal phase experienced increased uterine bleeding (reference: menstrual period, OR = 4.33, 95% CI 1.23-15.25, p = .023). The results suggested non-inferiority of goserelin therapy initiated during the non-menstrual period, but the uterine bleeding rate was higher in the luteal phase group. Therefore, goserelin treatment for outpatient adenomyosis patients should not be limited to starting during the menstrual period; it can also be initiated outside the menstrual period, providing more convenience for patients as most consultations occur outside the menstrual period. However, the use of goserelin during the luteal phase should be avoided to reduce the risk of exacerbated bleeding, especially in anemic patients with heavy menstrual bleeding. This study highlights the importance of individualizing treatment initiation based on the patient's health profile to optimize therapeutic outcomes and minimize adverse effects. ChiCTR2200059548.

Evaluation of goserelin effectiveness based on assessment of inflammatory cytokines and symptoms in uterine leiomyoma.

Background Uterine leiomyoma is a benign tumour of the uterine smooth muscles associated with an elevated level of inflammatory cytokines. Goserelin, a synthetic gonadotropin-releasing hormoneanalogue, suppresses the production of sex hormones and release of inflammatory cytokines in uterine leiomyoma cells. Objective The primary objective of this study was to find out the effectiveness of subcutaneous goserelin therapy on lowering serum levels of inflammatory cytokines and improving uterine leiomyoma-related symptoms in female patients diagnosed with uterine leiomyoma. The secondary objective was to assess the tolerability to goserelin therapy used in the management of this tumour. Setting Outpatient gynaecological clinic of the medical consultation department of Baghdad Teaching Hospital, Baghdad province, Iraq. Methods A single centre, prospective, longitudinal, cohort study was carried out on female patients diagnosed with uterine leiomyoma. Goserelin 3.6mg subcutaneous injection was given in a consecutive monthly dose for the total time duration of three months. Serum levels of inflammatory cytokines, tumour necrosis factor-α and monocyte chemotactic protein-1 were detected before and after goserelin therapy in a consecutive monthly assessment. The study also assessed the improvement in uterine leiomyoma-related symptoms, including pelvic pain alongside the incidence of goserelin-related side effects during therapy schedules. Main Outcome Measures Assessment of serum levels of tumour necrosis factor-α and monocyte chemotactic protein-1 alongside uterine leiomyoma-related symptoms, including pelvic pain and goserelin-related side effects. Results There was a significant decrease in serum levels of tumour necrosis factor-α and monocyte chemotactic protein-1 compared to the baseline level over the 3-month duration of goserelin therapy (0.11 ± 0.02 vs. 0.74 ± 0.19) pg/mL; (0.07 ± 0.00 vs. 0.44 ± 0.18) pg/mL respectively. Patients showed a clinical improvement regarding uterine leiomyoma-related symptoms following each of the consecutive monthly doses of goserelin therapy (n = 11, 55%, P < 0.0001; n = 15, 75%, P < 0.0001; n = 18, 90%, P < 0.0001) respectively. This also includes a significant decrease in the intensity of leiomyoma-related pelvic pain before and after goserelin therapy (7.2 ± 1.43 vs. 3.05 ± 1.14, P < 0.0001). The majority of patients reported vaginal dryness (60%) as the main goserelin-related side effect. Conclusion Goserelin therapy reduces serum levels of inflammatory cytokines, tumour necrosis factor- α and monocyte chemotactic protein-1, improving leiomyoma-related symptoms with good tolerability in patients with uterine leiomyoma.

Switching to anastrozole plus goserelin vs continued tamoxifen for adjuvant therapy of premenopausal early-stage breast cancer: preliminary results from a randomized trial.

PurposeTo assess the efficacy, safety, and quality-of-life impact of switching adjuvant treatment in hormone receptor-positive primary breast cancer patients who are still premenopausal after 2–3 years of tamoxifen therapy to anastrozole plus goserelin as compared with continuing tamoxifen over a total period of 5 years.Patients and methodsHormone receptor-positive, premenopausal, lymph node-positive, or tumor size ≥4 cm breast cancer patients who had received tamoxifen for 2–3 years were randomly assigned to continue tamoxifen treatment (TAM group) or switch to adjuvant anastrozole plus goserelin (ADD group) and continue treatment for another 2–3 years (total treatment duration 5 years). Endpoints evaluated were adverse events (AEs), changes in bone mineral density, quality of life, and disease-free survival-related events.ResultsA total of 62 patients (33 in the ADD group and 29 in the TAM group) were evaluated. Grade 3–4 drug-related AEs occurred in five patients (15.2%) in the ADD group vs none in the TAM group. In the ADD group, arthralgias were the most common AEs (5/33 patients; 15.2%), and three patients in this group were discontinued because of AEs. Treatment was temporarily suspended due to AEs in three patients (9.1%) in the ADD group and one patient (3.4%) in the TAM group. Compared with continuing TAM therapy, switching to anastrozole plus goserelin did not result in any worsening of bone mineral density or quality of life. During a median follow-up of 34 months, five patients (15.2%) in the ADD group had disease-free survival events vs four patients (13.8%) in the TAM group.ConclusionFor early-stage breast cancer patients who remain premenopausal following 2–3 years of adjuvant tamoxifen therapy, switching to anastrozole plus goserelin therapy was safe with tolerable adverse effects. However, it did not show superior efficacy compared to remaining on tamoxifen treatment.Trial RegistrationClinicalTrials.gov (identifier NCT01352091).

Phase II trial of goserelin and exemestane combination therapy in premenopausal women with locally advanced or metastatic breast cancer.

e11525 Background: A promising option as the treatment of choice for premenopausal patients with locally advanced or metastatic breast cancer (MBC) could be the combination of a luteinising hormone-releasing hormone analog and an aromatase inhibitor. However, no prospective studies on the efficacy of goserelin with exemestane in locally advanced or MBC premenopausal breast cancer patients have been reported. Methods: We present the phase II trial of goserelin plus exemestane in a total of 44 premenopausal women with locally advanced or MBC. All patients received a subcutaneous injection of 3.6 mg of goserelin every 4 weeks along with exemestane 25 mg daily. The primary end point was progression-free survival (PFS). The second end point included overall survival (OS), objective rate of response (RR), duration of response (DOR), and clinical benefit rate (CBR) based on complete response (CR), partial response (PR), or stable disease (SD) for ≥ 6 months. Results: The median PFS was 13 months (range: 2–42 mon...

Zoledronic acid combined with adjuvant endocrine therapy of tamoxifen versus anastrozol plus ovarian function suppression in premenopausal early breast cancer: final analysis of the Austrian Breast and Colorectal Cancer Study Group Trial 12

Zoledronic acid (ZOL) plus adjuvant endocrine therapy significantly improved disease-free survival (DFS) at 48- and 62-month follow-up in the ABCSG-12 trial. We present efficacy results of a final additional analysis after 94.4 months. Patients were premenopausal women who had undergone primary surgery for stage I/II estrogen-receptor-positive and/or progesterone-receptor-positive breast cancer with <10 positive lymph nodes, and were scheduled for standard goserelin therapy. All 1803 patients received goserelin (3.6 mg every 28 days) and were randomized to tamoxifen (20 mg/days) or anastrozole (1 mg/days), both with or without ZOL (4 mg every 6 months) for 3 years. The primary end point was DFS; recurrence-free survival and overall survival (OS) were secondary end points. After 94.4-month median follow-up (range, 0-114 months), relative risks of disease progression [hazard ratio (HR) = 0.77; 95% confidence interval (CI) 0.60-0.99; P = 0.042] and of death (HR = 0.66; 95% CI 0.43-1.02; P = 0.064) are still reduced by ZOL although no longer significant at the predefined significance level. Overall, 251 DFS events and 86 deaths were reported. Absolute risk reductions with ZOL were 3.4% for DFS and 2.2% for OS. There was no DFS difference between tamoxifen alone versus anastrozole alone, but there was a pronounced higher risk of death for anastrozole-treated patients (HR = 1.63; 95% CI 1.05-1.45; P = 0.030). Treatments were generally well tolerated, with no reports of renal failure or osteonecrosis of the jaw. These final results from ABCSG 12 suggest that twice-yearly ZOL enhances the efficacy of adjuvant endocrine treatment, and this benefit is maintained long-term. NCT00295646 (http://www.clinicaltrials.gov/ct2/results?term=00295646).

Endometriosis of the Vermiform Appendix within a Hernia Sac Infiltrating the Pubic Bone.

Purpose. Appendicular endometriosis mimicking appendicitis is a rare finding. Inguinal tumor in the course of appendicular endometriosis located within an inguinal hernia sac and infiltrating the periosteum of the pubic bone has not yet been described. Case Report. This paper describes a case of a rapidly enlarging, solid, unmovable, very painful upon palpation inguinal tumor, in a 36-year-old nulliparous woman. During surgery, a hard (approximately 4 cm in diameter) tumor infiltrating the periosteum of the right pubic bone and continuous with the inguinal hernia sac was dissected. The distal segment of the vermiform appendix was an element of the dissected tumor. Histological examination revealed endometriosis of the distal vermiform appendix. After 6 months of hormone treatment, she was referred for reoperation due to tumor recurrence. Once again histological examination of the resected tissue revealed endometriosis. There was no further recurrence of the disease with goserelin therapy. In addition to the case report, we present a review of the literature about endometriosis involving the vermiform appendix and the inguinal canal (Amyand's hernia). Conclusion. This case expands the list of differential diagnoses of nodules found in the inguinal region of women.

Resolution of Catamenial Epilepsy after Goserelin Therapy and Oophorectomy: Case Report of Presumed Cerebral Endometriosis

Endometriosis can develop in every organ and tissue in the female body except perhaps the spleen. The mechanism of distal metastasis is thought to be hematogenous or lymphatic spread from the uterus. Endometriotic lesions in the central nervous system are rare. Herein, we report the case of a woman with abnormal uterine bleeding who developed catamenial neurologic signs and symptoms. Computed tomography scans and magnetic resonance images demonstrated a circumscribed lesion in the left centrum semiovale of the brain. All neurologic symptoms resolved completely after treatment with gonadotropin-releasing hormone agonist for 3 months and subsequent laparoscopic bilateral oophorectomy. The patient was thought to have cerebral endometriosis, a rare phenomenon, although several cases have been reported in the literature. Temporal association of neurologic signs and symptoms with menstruation that resolves with medical or surgical menopause is highly suggestive of cerebral endometriosis.

Randomized Comparison of Goserelin Versus Suction Curettage Prior to Thermachoice II Balloon Endometrial Ablation: One-year Results

ObjectivesTo evaluate the clinical outcomes following the use of goserelin and suction curettage prior to ThermaChoice II balloon endometrial ablation to treat menorrhagia. MethodsQualified patients (n = 105) were randomized to receive either goserelin 3.6mg one month before or suction curettage immediately before undergoing thermal balloon endometrial ablation. All patients had negative Papanicolaou smears, normal endometrial histology, and normal findings on transvaginal sonography. Uterine bleeding was documented by menstrual diary scores at baseline (Higham score > 150), and at three, six, and 12 months after the procedure. Five patients withdrew prior to surgery and 50 patients were anaesthetized in each group. Two patients in the suction curettage group had their management converted to hysteroscopic ablation, one because of a large uterine cavity (>12 mL) and one because of a submucous myoma. The ThermaChoice II system circulated the liquid within the silicone balloon for eight minutes at approximately 180mmHg pressure and 87°C. ResultsParticipants’ mean age, weight, and duration of menorrhagia were not significantly different between the groups. No safety issues related to the device were noted. At one year after ablation, the median reduction in Higham score was from 286 to 10 (96.5%) in the goserelin group (n = 47), and from 272 to 14 (94.9%) in the curettage group (n = 45). The combined amenorrhea/hypomenorrhea rates (higham score 0 to 35), eumenorrhea rate (higham score 36 to 75) and menorrhagia rate (higham score > 75) were 85%, 9%, and 6% (goserelin), and 76%, 16%, 9% (curettage), respectively. Patients’ reported self-assessment of dysmenorrhea was none (51%), mild (30%), moderate (10%), and severe (9%) in both groups. Patient satisfaction was 89% in the goserelin group and 95% in the curettage group. In the goserelin group, one patient had a hysterectomy for bleeding and two had repeat resectoscopic endometrial ablations, one for pain (hematometra) and one for pain and bleeding. In the curettage group, one patient had repeat resectoscopic ablation, one patient withdrew, and one requested hormone therapy. The overall success rates were 88% in the goserelin group and 89% in the curettage group. ConclusionAt one year after ThermaChoice II treatment, 88.5% of women had normal menstrual bleeding or less. There was a non-significant trend (a lower Higham score) towards superiority of goserelin therapy before ablation compared with curettage.

Phase II Parallel Group Study Showing Comparable Efficacy Between Premenopausal Metastatic Breast Cancer Patients Treated With Letrozole Plus Goserelin and Postmenopausal Patients Treated With Letrozole Alone As First-Line Hormone Therapy

Goserelin and letrozole in premenopausal patients can result in clinical outcomes comparable to those obtained by letrozole alone in postmenopausal patients with metastatic breast cancer (MBC). A total of 73 patients with hormone-responsive MBC were included. Of those, 35 premenopausal patients received goserelin (3.6 mg subcutaneously every 28 days) plus letrozole (2.5 mg orally daily), and 38 postmenopausal patients received letrozole alone as their first-line endocrine therapy in a metastatic setting. Baseline characteristics were similar in the two groups, except for a younger age (median, 41 v 53.5 years; P < .001) and a shorter disease-free interval (median, 1.8 v 3.3 years; P = .03) in the premenopausal group. Clinical benefit rates were comparable between the two groups (77% v 74%; P = .77). With the median follow-up of 27.4 months, there was no statistical difference in the median time to progression between the two groups (9.5 months [95% CI, 6.4 to 12.1 months] v 8.9 months [95% CI, 6.4 to 13.3 months]). In patients who did not receive bisphosphonate, letrozole +/- goserelin caused a greater loss of bone mineral density at 6 months compared with that of patients receiving bisphosphonate treatment (premenopausal group, -16.7% v 53.9%; P = .002 and postmenopausal group, -13.3% v 17.4%; P = .04 at the lumbar spine). Clinical efficacies in premenopausal MBC patients with combined letrozole and goserelin therapy were comparable to those in postmenopausal patients treated with letrozole alone. Although letrozole +/- goserelin resulted in a modest increase in bone resorption, concurrent treatment with bisphosphonate could prevent bone loss at 6 months.

Initial growth deceleration during GnRH analogue therapy for precocious puberty

To compare the efficacy of goserelin and leuprolide on initial deceleration of growth and weight gain during the first 12 months of GnRH analogue treatment for precocious puberty. Retrospective cohort analysis. Forty children with precocious puberty treated with either goserelin or leuprolide (33 females, mean age 7.3 and 7.7 years, respectively, at the start of treatment). The primary outcomes were baseline-to-6-months and 6-months-to-12-months change in height standard deviation score (SDS) and body mass index (BMI). Relative tall stature was calculated as the difference between height SDS and mid-parental height (MPH) SDS at baseline. Goserelin and leuprolide were associated with similar suppression of serum LH during the first 12 months of treatment (P = 0.62). Greater relative tall stature was strongly associated with more advanced bone age, greater BMI SDS and with greater reduction in height SDS in the first 6 months. Adjusted for relative tall stature, goserelin therapy was associated with significantly greater suppression of growth than leuprolide (P = 0.025) in the first 6 months of treatment, with no subsequent change in the second 6 months. A similar, significant increase in BMI was seen with both analogues. Both GnRH analogues were associated with effective biochemical suppression of puberty; however, goserelin was more effective at reducing linear growth during the first 6 months. Relative tall stature was a major determinant of the initial response to treatment.

Comparable efficacies between premenopausal and postmenopausal metastatic breast cancer patients by letrozole with and without goserelin as first line hormone therapy: a phase II parallel group study.

Abstract Abstract #6134 Background: The use of goserelin in premenopausal patients(pts) is to produce castrated level of estradiol (E2), and the remaining peripheral E2 production is inhibited by letrozole, which would accomplish comparable clinical outcomes as in postmenopausal metastatic breast cancer (MBC) pts by letrozole alone.&amp;#x2028; Methods: Hormone receptor positive pre- and postmenopausal pts with MBC were eligible. Letrozole 2.5 mg once a day was administered with goserelin 3.6 mg every 4 weeks in premenopausal pts and serial serum E2, FSH, LH were measured. Bone mineral density (BMD) and serum bone turnover markers were also checked (n=34).&amp;#x2028; Results: Among total 78 pts enrolled, 32 pre- and 38 postmenopausal pts were assessed for efficacy and adverse events (AE). The median age was 42 years (range, 32–52) for pre- and 53 years (range, 33–70) for postmenopausal pts. Baseline characteristics were similar in the two groups, except for significantly longer disease free interval in postmenopausal pts (22.2 months vs. 41.2 months, P=0.01). Clinical benefit (CR+ PR+ SD ≥ 24 weeks) rates (62.5% vs. 68.4%, P=0.62), and objective response (CR + PR) rates (28.1 % vs. 23.7%, P=0.79) were comparable between the two groups. Median TTP was 8.6 months vs. 9.6 months (P=0.61) with a median follow-up of 11.6 months and 14.6 months, respectively. In multivariate analysis, strong ER status was significantly associated with clinical benefit rate (P=0.01), and HER2 positivity (P&amp;lt;0.001) and stage IV presentation (P=0.05) with shorter TTP. In premenopausal pts, the mean E2 level was dropped from 62.3 ± 81.8 pg/mL at baseline to 12.3 ± 2.2 pg/mL at week 2. AEs were mild with significantly more hot flushes in premenopausal pts. In premenopausal pts without bisphosphonate treatment, there was a trend of rising serum levels of osteocalcin (OC) (0% vs. 165%, P=0.065), bone alkaline phosphatase (bALP) (0% vs. 28%, P=0.055), and C-telopeptide (CTx) (0% vs. 108%, P=0.095), as well as a significant reduction in both lumbar spine (P=0.044) and femur (P=0.027) BMD. In contrast, in premenopausal pts with bone metastasis on bisphosphonate, there was no significant change in OC, bALP, CTx, and both BMD. In postmenopausal pts without bisphosphonate treatment, no significant change in OC, bALP, CTx, and femur BMD, while in pts with bone metastasis on bisphosphonate treatment, a significant decrease in OC (0% vs. -22%, P=0.050) and CTx (0% vs. -41%, P=0.020) and increase in both BMD (P=0.044, P=0.038 respectively) were observed.&amp;#x2028; Conclusions: Clinical efficacies by letrozole and goserelin therapy in premenopausal MBC pts were comparable to those in postmenopausal pts by letrozole with mild AEs. While a modest increase in both bone formation and resorption especially in premenopausal pts, concurrent bisphosphonate therapy could stabilize bone metabolism in patients even with bone metastasis.&amp;#x2028; Supported by NCC Grant No NCS-0610240-3. Letrozole for premenopausal group was supplied by Novartis. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 6134.

Cardiovascular Mortality After Androgen Deprivation Therapy for Locally Advanced Prostate Cancer: RTOG 85-31

Gonadotropin-releasing hormone (GnRH) agonists are associated with greater risk of coronary heart disease and myocardial infarction in men with prostate cancer, but little is known about potential impact on cardiovascular mortality. We assessed the relationship between GnRH agonists and cardiovascular mortality in a large randomized phase III trial of men treated with or without adjuvant goserelin after radiation therapy (RT) for locally advanced prostate cancer. Between 1987 and 1992, 945 men with locally advanced prostate cancer were randomly assigned to RT and adjuvant goserelin or RT alone. Fine and Gray's regression was used to evaluate treatment effect on cardiovascular mortality. Covariates included age, prevalent cardiovascular disease (CVD), hypertension, diabetes mellitus (DM), body mass index, race, Gleason score, stage, acid phosphatase level, prostatectomy history, and nodal involvement. After a median follow-up of 8.1 years, there were 117 cardiovascular-related deaths but no treatment-related increase in cardiovascular mortality. At 9 years, cardiovascular mortality for men receiving adjuvant goserelin was 8.4% v 11.4% for men treated without adjuvant goserelin (Gray's P = .17). In multiple regression analyses, treatment arm was not significantly associated with increased risk of cardiovascular mortality (adjusted hazard ratio [HR] = 0.73; 95% CI, 0.47 to 1.15; P = .16; when censoring at time of salvage goserelin therapy, HR = 0.99; 95% CI, 0.58 to 1.69; P = .97). Traditional cardiac risk factors, including prevalent CVD and DM, were significantly associated with greater cardiovascular mortality. GnRH agonists do not seem to increase cardiovascular mortality in men with locally advanced prostate cancer. Further studies are warranted to evaluate adverse effects of GnRH agonists in men with lower cancer-specific mortality.

What is the role of androgen deprivation therapy in the treatment of locally advanced prostate cancer?

This Practice Point commentary discusses the paper by Horwitz and colleagues, which reported the long-term results of the RTOG 92-02 trial in which patients with locally advanced, node-negative prostate cancer who were treated with neoadjuvant-concurrent hormone ablation therapy and external beam radiation therapy (70 Gy) were subsequently randomized to receive either no further androgen deprivation or long-term (2-year) goserelin therapy. The results at 10 years confirm biochemical and clinical outcome benefits with the use of long-term androgen deprivation therapy for patients treated with conventional-dose radiotherapy. How these results should best be incorporated into dose-escalated radiotherapeutic approaches remains unclear, however, and this issue requires further investigation.

Effects of gonadal steroid withdrawal on serum phosphate and FGF-23 levels in men

Fibroblast growth factor (FGF-23) is a novel phosphaturic factor. Current data suggest that serum phosphate, dietary phosphate and 1,25 dihydroxyvitamin D regulate circulating FGF-23 levels in vivo. We examined if hypogonadism-induced increases in serum phosphate are associated with increases in circulating FGF-23 in healthy men in the absence of dietary manipulation. 25 healthy men were administered goserelin acetate (GnRH analog) 3.6 mg subcutaneously every 4 weeks for 12 weeks to induce acute testosterone and estrogen deficiency. Subjects consumed an ad libitum diet. Morning fasting blood and urine samples were collected to measure serum phosphate, serum intact FGF-23, PTH, and the maximum tubular reabsorption of phosphate (T(m)P/GFR) at baseline, weeks 4 and 12. The changes in serum FGF-23 and phosphate at weeks 4 and 12 were compared to baseline using paired t-tests. Goserelin therapy decreased mean serum testosterone levels from 543+/-160 ng/dL to 33+/-15 ng/dL at week 4 (p<0.001), and to 20+/-10 ng/dL at week 12 (p<0.001). Serum phosphate increased significantly from 3.4+/-0.6 mg/dL to 3.9+/-0.4 mg/dL at week 4 (p=0.002), and to 4.3+/-0.4 mg/dL at week 12 (p<0.001). T(m)P/GFR increased significantly from 3.2+/-0.6 mg/dL to 3.6+/-0.5 mg/dL at week 4 (p<0.004), and to 4.1+/-0.6 mg/dL at week 12 (p<0.001). FGF-23 levels, however, did not change during the 12-week study. Gonadal steroid deprivation increased serum phosphate levels in men but did not affect serum FGF-23 concentrations. The absence of any change in circulating FGF-23 suggests that supraphysiologic levels of serum phosphate may be required to stimulate circulating FGF-23 or that FGF-23 production is primarily sensitive to changes in dietary phosphate or 1,25 dihydroxyvitamin D within this physiologic serum phosphate range.

Administration of goserelin acetate after uterine artery embolization does not change the reduction rate and volume of uterine myomas

To determine if goserelin immediately after uterine artery embolization (UAE) affected myoma reduction. Randomized pilot study (level 1). Teaching hospital. Twenty-six women. All patients underwent UAE, and then 12 patients received 10.8 mg of goserelin 24 hours later. The treatment group was 5 years older: 43 versus 37.7 years. Uterine and myoma volumes were measured by ultrasound 2 weeks before UAE and at 3, 6, and 12 months. Uterine and fibroid volumes. Pretreatment uterine volume was 477 versus 556 cm3, and dominant fibroid volume was 257 versus 225 cm3 in the control versus goserelin groups. Analysis of variance measurements indicated that the change over time did not significantly differ between the two groups. By 12 months, the control group had a mean uterine volume reduction of 58%, while the goserelin group had a reduction of 45%. Dominant fibroid changes over time did not differ between the two groups. At 12 months, the mean fibroid volume had decreased by 86% and 58% in the control and goserelin groups, respectively. The addition of goserelin therapy to UAE did not alter the reduction rate or volume of uterine myomas.

Goserelin

Goserelin (Zoladex), a gonadotropin-releasing hormone analogue, reduces plasma/serum estrogen levels in pre- or perimenopausal women (to postmenopausal levels), and is indicated in hormone receptor-positive early breast cancer in this population group. Adjuvant goserelin monotherapy has similar efficacy to adjuvant chemotherapy in pre- or perimenopausal women with early, hormone receptor-positive breast cancer. Furthermore, the addition of goserelin to adjuvant chemotherapy appeared to offer an advantage over chemotherapy alone in younger patients. Fewer patients remained amenorrheic after goserelin therapy than after chemotherapy. Complete endocrine blockade provided by the addition of tamoxifen to therapy including goserelin appears to improve outcomes. Thus, goserelin offers a valuable addition to the currently available options for treating pre- or perimenopausal women with hormone therapy-responsive early breast cancer, particularly for women wishing to regain ovarian function after treatment.

Auxological outcome and time to menarche following long‐acting goserelin therapy in girls with central precocious or early puberty

Following a successful clinical trial in 1996, the long-acting GnRH analogue goserelin (Zoladex LA 10.8 mg; Astra Zeneca) has been our preferred treatment for central early (CEP) or precocious puberty (CPP). However, some female patients have expressed concern about perceived weight gain during therapy and delay in the onset or resumption of menses on completion of therapy. The primary aim of this study was to investigate these concerns by determining the auxological parameters and timing of menarche or re-menarche in all girls with CEP/CPP who have completed a course of Zoladex LA treatment. The secondary aim was to assess auxological outcome in girls who have attained final height. Case records of all girls with idiopathic CEP/CPP or CEP/CPP secondary to CNS pathology treated with Zoladex LA since 1996 were reviewed. A total of 46 girls who have completed therapy were identified, of whom 11 had reached final height. measurements Height, weight and bone age (RUS (TW2) method) were measured before treatment, when Zoladex LA was stopped and at final height. Body mass index (BMI) was calculated as a clinical measure of body fatness. Pubertal status was assessed pre- and post-treatment by Tanner staging and pelvic ultrasonography. Timing of menarche or re-menarche following cessation of treatment was recorded. The mean (range) age of starting GnRH analogue therapy was 8.3 (1.8-10.5) years and the duration of treatment was 2.9 (0.7-8.9) years. Pre-treatment height was above average at 0.72 SD but had declined to 0.28 SD by the end of therapy. The 46 girls were heavier than average before treatment (Wt SDS 1.04) with no change in weight status on completion of therapy. Mean BMI SDS increased significantly from 0.93 to 1.2 during treatment, indicating that the girls became relatively fatter. Using recommended BMI cut-off values for defining overweight and obesity in children of the 85th and 95th centiles, 41% of the cohort were overweight and 28% were obese before treatment, rising to 59% and 39%, respectively, at the end of therapy. The average time interval to onset or resumption of menses after stopping treatment was 1.46 years (median 1.5, range 0.8-2.0 years). None of the following variables was found to be predictive of the time interval to menarche after completion of therapy: duration of treatment; chronological age; bone age; Tanner breast stage or uterine maturation at the end of treatment; the frequency of injections required to suppress puberty; or treatment with alternative GnRH analogue prior to Zoladex LA. Mean final height in 11 girls was 159.7 cm (-0.63 SD), close to the mean parental target height of 160.9 cm (-0.48 SD). Nine of the 11 girls (82%) attained final heights within or above their target range. In keeping with the whole cohort this subset of girls became fatter during treatment, although this difference was not statistically significant. However, they returned to their pretreatment size at final height (mean BMI SDS 1.18, 1.41 and 1.16 before, at the end of treatment and at final height, respectively). Our cohort of 46 girls treated with long-acting goserelin was already considerably overweight at the start of therapy and became fatter during treatment. However, adiposity appeared to return to pretreatment levels in the 11 girls followed up to final height. Most of the girls who have attained final height are within or above their expected target range. The relatively long time interval to menarche of 1.5 years after stopping treatment is unexplained but may reflect a residual suppressive effect on the hypothalamo-pituitary axis of this long-acting GnRH analogue. Anticipation of the timing of menarche has proved to be of value in planning when to stop therapy in girls in whom treatment is mainly for practical and/or psychological reasons.

Bone mineral density in premenopausal women treated for node-positive early breast cancer with 2 years of goserelin or 6 months of cyclophosphamide, methotrexate and 5-fluorouracil (CMF).

The purpose of this study was to compare changes in bone mineral density (BMD) in premenopausal patients with node-positive early breast cancer treated with goserelin (Zoladex) or cyclophosphamide, methotrexate and 5-fluorouracil (CMF). Patients ( n=1640) were randomized to goserelin (3.6 mg every 28 days for 2 years) or CMF (sixx28-day cycles) treatment. In a protocoled sub-study involving 96 patients from eight centers (goserelin: n=53; CMF: n=43), lumbar spine (L2-L4) and femoral neck BMD were assessed by dual X-ray absorptiometry at baseline and then annually for 3 years. At the end of the 2-year goserelin-treatment period, mean BMD losses for goserelin-treated and CMF-treated patients were -10.5% and -6.5% ( P=0.0005) for lumbar spine and -6.4% and -4.5% ( P=0.04) for femoral neck, respectively. At 3 years, partial recovery of BMD was observed in goserelin recipients. In contrast, mean BMD losses for the CMF group indicated persistent BMD loss. No significant differences in BMD were observed between groups at the 3-year assessment of the spine or femoral neck. In the CMF group, based on amenorrhea status at 48 weeks, BMD losses at the lumbar spine were greater for amenorrheic than non-amenorrheic patients. Ovarian suppression resulting in amenorrhea was closely related to BMD loss in both treatment groups. Overall, patients who received CMF did not show recovery of BMD throughout follow-up, whereas partial recovery was observed 1 year after cessation of goserelin therapy, associated with the return of ovarian function in the majority of patients.

Gonadotropin-releasing hormone agonist goserelin and hormone add-back therapy for endometriosis

Gonadotropin-releasing hormone agonist goserelin and hormone add-back therapy for endometriosis

Comparison of goserelin and leuprolide in combined androgen blockade therapy

Objectives. To perform exploratory analyses of data from a controlled trial that assessed the efficacy and tolerability of two antiandrogens, bicalutamide and flutamide, each combined with monthly depot preparations of leuprolide or goserelin, in patients with Stage D2 prostate cancer. One analysis compared goserelin plus antiandrogen therapy with leuprolide plus antiandrogen therapy; a second analysis compared the four combined androgen blockade (CAB) regimens. Methods. This was a randomized, multicenter trial, open-label for luteinizing hormone releasing hormone analogue (LHRH-A) therapy, double-blind for antiandrogen therapy, with a two-by-two factorial design. Eight-hundred thirteen patients were allocated in a ratio of 2:1 to goserelin therapy (3.6 mg every 28 days) or leuprolide therapy (7.5 mg every 28 days) and 1:1 to bicalutamide therapy (50 mg once a day) or flutamide therapy (250 mg three times a day). The end points of time to progression and survival were assessed with a median of 160 weeks of follow-up. Results. The percentages of progression events (70.9% versus 73.3%) and deaths (54.3% versus 56.8%) were similar for goserelin plus antiandrogen and leuprolide plus antiandrogen therapies. The hazard ratios for goserelin plus antiandrogen therapy to leuprolide plus antiandrogen therapy were 0.99 (95% confidence interval [CI] 0.84 to 1.18; P = 0.92) and 0.91 (95% CI 0.75 to 1.11; P = 0.34) for time to progression and survival, respectively. Goserelin plus antiandrogen and leuprolide plus antiandrogen therapies were generally well tolerated, and the side effects associated with depot administration occurred with a low frequency in the two groups. There were no significant differences among the goserelin plus bicalutamide, goserelin plus flutamide, or leuprolide plus bicalutamide therapy groups, but leuprolide plus flutamide therapy had a significantly poorer outcome than the other three therapies. The side-effect profiles for the four CAB groups were generally similar; diarrhea was more common among patients treated with flutamide and hematuria was more common among patients treated with bicalutamide. Conclusions. Although the results of these exploratory analyses should be interpreted with caution, they indicate that goserelin plus antiandrogen and leuprolide plus antiandrogen therapies are similarly well tolerated and have equivalent time to progression and survival, and that leuprolide plus flutamide therapy appears to be the least effective of the four CAB regimens.