leuprolide and Hot-Flashes

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

Low-dose add-back therapy during postoperative GnRH agonist treatment could lower the risk of add-back-induced endometriosis recurrence and reduce treatment dropout compared with a regular dose. However, the effect of low-dose add-back therapy is still unknown. The aim of this study was to determine whether low-dose add-back therapy can also effectively relieve the hypoestrogenic side effects and simultaneously maintain a therapeutic response of GnRH agonist treatment.. This analysis was a prospective cohort study. During postoperative GnRH agonist treatment, a total of 107 women were prescribed add-back therapy [oral combination tablet; estradiol valerate (1 mg) and medroxyprogesterone acetate (2.5 mg)] (Indivina; Orion, Espoo, Finland) for 20 weeks. Patients in the low dose add-back therapy group were prescribed the tablet once a day, and patients in the regular dose group were given the tablet twice a day. Hypoestrogenic side effects, such as hot flashes and insomnia, were recorded. Patients were also questioned regarding their pelvic symptoms and pain to evaluate the possibility of endometriosis recurrence. Lumbar spine (L2-L4) bone mineral density was measured using dual X-ray absorptiometry. The dropout rates in both groups were also evaluated.. The incidence of hypoestrogenic side effects was lower in the low dose group compared with the regular dose group, including hot flashes (19.2% vs. 21.8%, p = 0.741) and insomnia (15.4% vs. 18.2%, p = 0.699), although there were no significant difference between the groups. In addition, a higher number of patients in the regular dose group dropped out of treatment compared to the low dose group (14.5% and 9.6%, respectively, p = 0.435). The patients in both groups had a significant loss of mean bone mineral density during therapy (p < 0.001 and p = 0.018 for the low dose and regular dose groups, respectively).. Low dose add-back therapy could effectively ameliorate hypoestrogenic side effects and simultaneously maintain the therapeutic response of GnRH agonist treatment. The treatment dropout was lower compared with a regular dose. Therefore, low dose add-back therapy can be considered a treatment choice during postoperative GnRH agonist treatment.

Topics: Adult; Bone Density; Drug Combinations; Endometriosis; Estradiol; Female; Gonadotropin-Releasing Hormone; Hormone Replacement Therapy; Hot Flashes; Humans; Leuprolide; Medroxyprogesterone Acetate; Patient Dropouts; Prospective Studies; Sleep Initiation and Maintenance Disorders

Leuprorelin is a well known luteinizing hormone releasing hormone agonist. However, there are insufficient data on the efficacy and safety of high dose leuprorelin acetate, especially in Asian patients with prostate cancer. We aimed to investigate the safety and efficacy of leuprorelin acetate 22.5 mg administered at three-month intervals in patients with prostate cancer.. In an open, prospective clinical trial enrolling 47 patients, we aimed to assess the efficacy and safety of leuprorelin acetate 22.5 mg in treating patients with histologically confirmed prostate cancer. The primary objective of this study was to evaluate the efficacy of the leuprorelin acetate 22.5 mg in producing and maintaining castration levels of testosterone over a 6-month follow-up period and to determine its safety profile.. All 42 patients achieved serum testosterone levels within the castration range by 4 weeks. A breakthrough response was observed in one of 36 patients by 8 weeks. However, this patient was medically castrated by 12 weeks. There were no significant prostate-specific antigen (PSA) or testosterone changes according to clinical stage or body mass index. Twenty adverse events (AEs) in 15 of 42 patients (35.7%) were observed during this study. The most common AEs were hot flushes (n=4, 20.0%) with mild intensity, pain (n=2, 10.0%), and infection (n=2, 10.0%). No patient withdrew from the study due to AEs.. Leuprorelin acetate 22.5 mg was shown to be effective and safe in Asian patients with prostate cancer, even though sexual function decreased.

Topics: Aged; Aged, 80 and over; Antineoplastic Agents, Hormonal; Asian People; Drug Administration Schedule; Hot Flashes; Humans; Leuprolide; Male; Middle Aged; Penis; Prostate-Specific Antigen; Prostatic Neoplasms; Testis; Testosterone; Treatment Outcome

To identify the factors underlying prostate cancer (PCa) patients' depression-anxiety, sexual problems, urinary dysfunction and androgen deprivation therapy (ADT)-linked breast changes and hot flushes, and test these as predictors of loss of masculinity (LoM) over 36 months following diagnosis.. One thousand seventy patients from the TROG 03.04 (RADAR) trial the EORTC QLQ C-30 and PR 25 questionnaires, and the International Prostate Cancer Symptom Score of the American Urological Association at baseline, 3, 7, 12, 18, 24 and 36 months. Selected items from these scales were factor-analysed to identify a four-component solution for responses at 18 and 36 months, and these components were regressed against a single-item measuring LoM.. Depression-anxiety factor was the most powerful predictor of LoM at both time points, followed by sexual problems of ADT side effects (breast changes and hot flushes). Urinary dysfunction was not a consistent predictor of LoM. Depression-anxiety was also the most significant factor distinguishing between those men who reported LoM and those who did not.. Although LoM is often reported as arising from ADT, the relative power of depression-anxiety in predicting LoM, both at the selected time points and using a time-lagged analysis, plus the finding that depression-anxiety was the most consistent difference between men who reported LoM and those who did not, argues for the presence of adverse mood states as being the key ingredient in deciding if PCa patients experience loss of their feelings of masculinity.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Androgen Antagonists; Antineoplastic Agents, Hormonal; Anxiety; Depression; Hot Flashes; Humans; Leuprolide; Male; Masculinity; Middle Aged; Prostatic Neoplasms; Sexual Dysfunction, Physiological; Surveys and Questionnaires

Approximately 60-70 percent of women with premenstrual dysphoric disorder (PMDD) show symptomatic improvement in response to the GnRH agonist leuprolide acetate, which suppresses ovarian function. However, it has been very difficult to either predict or understand why some women respond, while others do not. We applied several complementary statistical methods to the dynamics of pre-treatment mood rating data to determine possible predictors of response for women with PMDD. We compared responders (n = 33) to nonresponders (n = 12) in clinical trials of leuprolide (three months in duration) as a treatment for PMDD, on the basis of pre-trial daily self-ratings of sadness, anxiety, and irritability. We analyzed both sequential irregularity (approximate entropy, ApEn) and a quantification of spikiness of these series, as well as a composite measure that equally weighted these two statistics. Both ApEn and Spikiness were significantly smaller for responders than nonresponders (P ≤ 0.005); the composite measure was smaller for responders compared with nonresponders (P ≤ 0.002) and discriminated between the subgroups with high sensitivity and specificity. In contrast, mean symptom levels were indistinct between the subgroups. Relatively regular and non-spiky pre-trial dynamics of mood ratings predict a positive response to leuprolide by women with PMDD with high probability, moreover based on typically less than 3 months of daily records. The statistical measures may have broad and direct applicability to behavioral studies for many psychiatric disorders, facilitating both accurate diagnosis and the prediction of response to treatment.

Topics: Adult; Entropy; Female; Fertility Agents, Female; Hormones; Hot Flashes; Humans; Leuprolide; Mood Disorders; Nonlinear Dynamics; Predictive Value of Tests; Premenstrual Syndrome; Psychiatric Status Rating Scales; Statistics, Nonparametric; Young Adult

To investigate the impacts of leuprolide acetate on the quality of life (QoL) of patients with prostate cancer.. A total of 104 patients was enrolled in this prospective multicenter study. All patients received subcutaneous injections of 3.75 mg leuprolide acetate at 4 week intervals for a total of 12 weeks. QoL was assessed before treatment and at 12 weeks using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) and an accompanying prostate cancer-specific module (QLQ-PR25).. Eighty-nine of 104 patients (85.6%) completed the 12 week study. Eighty-six of 89 patients (96.6%) achieved and maintained medical castration. The results of the EORTC QLQ-C30 indicated that patients experienced an improvement in global health status/QoL (p < 0.001), despite a deterioration in physical and role functioning (p = 0.012 and p = 0.007, respectively). The symptom scales indicated a statistically significant improvement in appetite (p = 0.003). The results of the QLQ-PR25 revealed that patients experienced an increase in hot flushes (p < 0.001) and erection problems and uncomfortable sexual intimacy among the sexual functioning items (p = 0.030 and p = 0.023, respectively), but day-time urinary frequency was improved (p = 0.004).. The results of this prospective study indicate that leuprolide acetate treatment was accompanied by improvements in global health status/QoL, despite a deterioration in physical, role and sexual function.

Topics: Aged; Aged, 80 and over; Antineoplastic Agents, Hormonal; Castration; Chemotherapy, Adjuvant; Hot Flashes; Humans; Leuprolide; Male; Middle Aged; Prospective Studies; Prostatic Neoplasms; Quality of Life; Republic of Korea; Sexual Dysfunction, Physiological; Sexual Dysfunctions, Psychological; Statistics, Nonparametric; Surveys and Questionnaires; Urination Disorders

To investigate hot flashes and quality of life during combined androgen blockade (CAB) therapy using steroidal or nonsteroidal antiandrogens.. A total of 151 patients with prostate cancer, who were enrolled into this study from May 2001 to June 2003, were randomized to receive CAB therapy using a luteinizing hormone-releasing hormone agonist (leuprorelin) combined with a steroidal antiandrogen (chlormadinone) or a nonsteroidal antiandrogen (bicalutamide). The incidence of, frequency of, and distress due to hot flashes were evaluated with a self-administered questionnaire during a 2-year period. The general and disease-specific quality-of-life outcomes were also measured using the Functional Assessment of Cancer Therapy-Prostate questionnaire.. Data were available for analysis from 124 patients. Although the incidence of hot flashes largely tended to be greater in the bicalutamide group than in the chlormadinone group, no significant difference was noted in the cumulative incidence of hot flashes at 2 years. The median frequency of hot flashes daily was 1.3 and 2.2 for warmth/flushing (P = .16) and 1.0 and 3.6 for sweating (P = .021) in the chlormadinone and bicalutamide groups, respectively. Patients in the chlormadinone group were significantly less likely to be distressed by warmth/flushing (odds ratio 0.47, P < .001) and sweating (odds ratio 0.61, P = .01) than were those in the bicalutamide group. The Functional Assessment of Cancer Therapy-Prostate scores over time showed no intergroup differences.. Our results suggest that CAB using a steroidal antiandrogen such as chlormadinone might induce fewer and less-distressing hot flashes than CAB with bicalutamide.

Topics: Aged; Androgen Antagonists; Anilides; Antineoplastic Agents, Hormonal; Chlormadinone Acetate; Drug Therapy, Combination; Gonadotropin-Releasing Hormone; Hot Flashes; Humans; Leuprolide; Male; Nitriles; Prospective Studies; Prostatic Neoplasms; Quality of Life; Steroids; Tosyl Compounds

To evaluate the clinical features and the expression of transforming growth factor-beta3 (TGF-beta3) and connective tissue growth factor (CTGF) in myometrium and uterine leiomyomas after preoperative treatment with gonadotropin-releasing hormone-analogs (GnRH-a) and tibolone.. Twenty-three patients received 3.75 mg leuprolide acetate depot for 4 months. Twenty-two patients received the same therapy plus 2.5 mg tibolone daily. Patients underwent uterine surgery after therapy. Twenty-two untreated patients underwent surgery directly. Hematologic tests, bone mineral density (BMD) measurement, and ultrasonographic evaluation of uterine volume were performed before and after treatment. Menorrhagia and pelvic pain were evaluated with a visual analog scale. Hot flushes were recorded in daily diaries. Immunohistochemical expression of TGF-beta3 and CTGF in myometrium and myoma samples was evaluated semiquantitatively.. After therapy, hemoglobin and iron levels similarly increased in both groups. BMD significantly decreased only in the GnRH-a group. Uterine volume similarly decreased in both groups. No patient had menorrhagia or pelvic pain at the end of therapy. The number of hot flushes increased after the first month in the GnRH-a group; in the GnRH-a plus tibolone group, it remained constant and was lower. In untreated cases, TGF-beta3 and CTGF smooth muscle cell immunoexpression was lower in myometrium than in leiomyomas. After medical treatment, growth factor immunoexpression remained unchanged in myometrial samples and was reduced in leiomyomas. Endothelial cells showed strong immunopositivity, both in untreated and in treated cases.. This study focuses on the effects of GnRH-a and tibolone on TGF-beta3 and CTGF expression in myometrium and myomas and supports the hypothesis of a pathogenetic role of these growth factors in uterine fibromatosis.

Topics: Adult; Antineoplastic Agents, Hormonal; Bone Density; Connective Tissue Growth Factor; Drug Therapy, Combination; Female; Hemoglobins; Hot Flashes; Humans; Immediate-Early Proteins; Immunohistochemistry; Injections, Subcutaneous; Intercellular Signaling Peptides and Proteins; Iron; Leiomyoma; Leuprolide; Myometrium; Neoadjuvant Therapy; Norpregnenes; Transforming Growth Factor beta; Transforming Growth Factor beta3; Uterine Neoplasms

Raloxifene hydrochloride is a synthetic non-steroidal drug used for the prevention and treatment of post-menopausal osteoporosis. Pre-clinical and clinical data have shown that raloxifene may have a beneficial effect on leiomyomas. The aim of this prospective single-blind, randomized, placebo-controlled clinical trial was to evaluate the effectiveness of the addition of raloxifene to GnRH analogues on uterine, leiomyoma, and non-leiomyoma sizes, and on the occurrence of leiomyoma-related symptoms.. After randomization using a computer-generated list, 100 pre-menopausal women with symptomatic uterine leiomyomas received either leuprolide acetate depot plus raloxifene 60 mg daily (group A) or leuprolide plus placebo tablet (group B) for six cycles of 28 days. At baseline and after treatment, uterine, leiomyoma and non-leiomyoma sizes, and leiomyoma-related symptoms were evaluated for each woman. Analysis was by intention-to-treat method.. After six cycles of treatment, a significant decrease in uterine, leiomyoma, and non-leiomyoma sizes was detected in both groups in comparison with baseline. At the same time, no significant difference in uterine and non-leiomyoma sizes was observed between the groups. Leiomyoma sizes were significantly (P < 0.05) lower in group A than in group B. No difference was observed in leiomyoma-related symptoms between groups throughout the study period.. In women treated with GnRH analogue, the raloxifene administration induces a higher reduction of leiomyoma sizes.

Topics: Delayed-Action Preparations; Female; Hot Flashes; Humans; Leiomyoma; Leuprolide; Menorrhagia; Pain; Patient Dropouts; Placebos; Premenopause; Prospective Studies; Raloxifene Hydrochloride; Selective Estrogen Receptor Modulators; Ultrasonography; Uterine Neoplasms

To evaluate the effectiveness of GnRH agonist (GnRH-a) plus tibolone in the treatment of severe premenstrual syndrome (PMS).. Prospective, double-blind, placebo-controlled clinical trial.. Department of Obstetrics and Gynecology, University of Naples Federico II, Naples, Italy. PATIENT(S); Thirty patients affected by severe PMS, aged 23-29 years (mean age +/- SD, 25.3 +/- 2.9 years).. Treatment for two cycles with leuprolide acetate depot (3.75 mg IM for 28 days) in association with tibolone (2.5 mg/d orally) or placebo (1 tablet per day orally).. The mean severity of each symptom and sign of PMS was evaluated using a visual analog scale during the last 7 days of each treatment cycle in comparison with the last 7 days of the cycle before treatment.. Mean scores for each of the adverse psychological/physical and positive psychological symptoms were significantly improved during treatment. No statistically significant difference was detected between patients treated with tibolone and placebo. A significantly lower number of hot flushes per day was observed in groups treated with GnRH-a and tibolone in comparison with GnRH-a and placebo.. Tibolone administered in association with GnRH-a does not reduce the therapeutic effect of GnRH-a in women affected by PMS. Tibolone used in association with GnRH-a may provide long-term medical treatment for women with PMS.

Topics: Adult; Anabolic Agents; Double-Blind Method; Drug Therapy, Combination; Female; Hot Flashes; Humans; Leuprolide; Norpregnenes; Placebos; Premenstrual Syndrome; Prospective Studies

To evaluate whether administration of tibolone changes the effectiveness of GnRH analogue administered before laparoscopic myomectomy.. Prospective, randomized, open, placebo-controlled clinical trial.. Department of Gynecology and Obstetrics, University of Naples Federico II, Naples, Italy.. 66 women with symptomatic uterine leiomyomas.. Treatment for 2 months with leuprolide acetate and iron tablets, plus tibolone (group A) or placebo tablets (group B); or with leuprolide acetate and iron tablets (group C).. Laparoscopic myomectomy at the end of treatment. Operative time and blood loss during surgery were recorded. Uterine volume, volume and number of uterine leiomyomas, volume and echogenicity of the largest uterine leiomyomas, hematologic data, and myoma-related symptoms were evaluated at baseline and 1 week before and after surgery.. Uterine and leiomyomata volume and myoma-related symptoms were significantly reduced and hematologic variables improved significantly in groups A and B, compared with baseline values and with group C. Operative time and blood loss were significantly less in groups A and B than in group C. After surgery, hematologic variables were significantly worse in group C compared with groups A and B. During the study no significant difference was detected between groups A and B.. Administration of tibolone administration in patients treated with GnRH analogue before laparoscopic myomectomy does not change the effectiveness of the analogue administered alone.

Topics: Adult; Combined Modality Therapy; Female; Gonadotropin-Releasing Hormone; Hot Flashes; Humans; Iron; Laparoscopy; Leiomyoma; Leuprolide; Norpregnenes; Placebos; Prospective Studies; Treatment Outcome; Uterine Neoplasms

The purpose of this study was to determine estrogen (E(2)) and progesterone (P(4)) effects on atrial natriuretic peptide (ANP) control of plasma volume (PV) and transcapillary fluid dynamics. To this end, we suppressed reproductive function in 12 women (age 21-35 yr) using a gonadotropin releasing-hormone (GnRH) analog (leuprolide acetate) for 5 wk. During the 5th week, the women either received 4 days of E(2) administration (17beta-estradiol, transdermal patch, 0.1 mg/day) or 4 days of E(2) with P(4) administration (vaginal gel, 90 mg P(4) twice per day). At the end of the 4th and 5th week of GnRH analog and hormone administration, we determined PV (Evans blue dye) and changes in PV and forearm capillary filtration coefficient (CFC) during a 120-min infusion of ANP (5 ng x kg body wt(-1) x min(-1)). Preinfusion PV was estimated from Evans blue dye measurement taken over the last 30 min of infusion based on changes in hematocrit. E(2) treatment did not affect preinfusion PV relative to GnRH analog alone (45.3 +/- 3.1 vs. 45.4 +/- 3.1 ml/kg). During ANP infusion CFC was greater during E(2) treatment compared with GnRH analog alone (6.5 +/- 1.4 vs. 4.9 +/- 1.4 microl. 100 g(-1) x min(-1) mmHg(-1), P < 0.05). The %PV loss during ANP infusion was similar for E(2) and GnRH analog-alone treatments (-0.8 +/- 0.2 and -1.0 +/- 0.2 ml/kg, respectively), indicating the change in CFC had little systemic effect on ANP-related changes in PV. Estimated baseline PV was reduced by E(2)-P(4) treatment. During ANP infusion CFC was approximately 30% lower during E(2)-P(4) (6.0 +/- 0.5 vs. 4.3 +/- 4.3 microl. 100 g(-1) x min(-1) mm Hg(-1), P < 0.05), and the PV loss during ANP infusion was attenuated (-0.9 +/- 0.2 and -0.2 +/- 0.2 ml/kg for GnRH analog-alone and E(2)-P(4) treatments, respectively). Thus the E(2)-P(4) treatment lowered CFC and reduced PV loss during ANP infusion.

Topics: Adult; Atrial Natriuretic Factor; Blood Pressure; Blood Volume; Capillaries; Capillary Permeability; Cardiac Output; Drug Administration Routes; Estradiol; Estrogens; Female; Fertility Agents, Female; Forearm; Gonadotropin-Releasing Hormone; Hematocrit; Hot Flashes; Humans; Infusions, Intravenous; Leuprolide; Progesterone; Stroke Volume; Veins

To assess the effectiveness and tolerability of transdermal estrogen in men with hot flushes after hormonal therapy for prostate cancer.. Twelve men with moderate to severe hot flushes were randomized to receive either low-dose (0.05 mg) or high-dose (0.10 mg) estrogen patches applied twice weekly for 4 weeks. After a 4-week washout period in which no treatment was given, each patient received the alternative dose for 4 weeks. Treatment response was assessed by daily logs and questionnaires completed every 4 weeks that included a visual analog assessment. Serum luteinizing hormone, follicle-stimulating hormone, testosterone, and estradiol levels were also measured every 4 weeks during the study.. There was a significant reduction in the overall severity of the hot flushes seen in patients with both the low and high-dose estrogen patch. A significant reduction in the daily frequency of the hot flushes was seen with the high-dose patch only. Overall, 10 (83%) of 12 men reported either mild, moderate, or major improvement in symptoms with either the low or high-dose patch. Mild, painless breast swelling or nipple tenderness was noted in 2 (17%) and 5 (42%) of 12 men treated with the low and high-dose estrogen patch, respectively. FSH levels decreased significantly with both the low and high-dose patch. Estradiol levels increased from 12.1 to 16.4 pg/mL and 26.9 pg/mL with the low and high-dose patch, respectively. There was no significant change in serum testosterone or luteinizing hormone levels.. Transdermal estrogen appears to be a promising, well-tolerated therapy for men with hot flushes after endocrine treatment for prostate cancer. Further study in larger groups of patients is necessary to assess the relative effectiveness and morbidity of this treatment.

Topics: Administration, Cutaneous; Aged; Aged, 80 and over; Antineoplastic Agents, Hormonal; Estrogens; Hot Flashes; Humans; Leuprolide; Male; Middle Aged; Prostatic Neoplasms

In order to assess the endocrinological changes associated with 2 types of low-dose GnRH agonists depot as well as their clinical efficacy, we performed a randomized prospective comparison study of patients having uterine leiomyomas or endometriosis.. A prospective randomized study involving 67 patients with uterine leiomyomas or endometriosis was carried out. These patients were randomly administered either buserelin MP 1.8 mg (Group B, n = 34) or leuprolide 1.88 mg (Group L, n = 33). In each group we evaluated the symptoms of genital bleeding and hot flashes during GnRHa treatment, as well as the levels of serum LH, FSH, and estradiol 8 weeks after the start of treatment. In addition, the endometrial thickness was measured by transvaginal ultrasonography, and changes in the volume of the uterine leiomyoma or endometrial cyst at the end of treatment. The GnRHa depot was administered from 3 to 8 times, 28 days apart, in both groups.. The incidence of menstruation-like genital bleeding 8 weeks after treatment was significantly (p < 0.01) higher in Group B. However this difference disappeared by 12 weeks after treatment. The climacteric symptom of hot flashes was found to be significantly (p < 0.01) more severe in Group L, and this tendency continued until 20 weeks after treatment. The 2 groups did not differ significantly with regard to the levels of the serum LH, FSH, and estradiol at 8 weeks after treatment or in the endometrial thickness at the end of the GnRHa treatment. In both groups, the volumes of the uterine leiomyomas were significantly (p < 0.01) lower after the treatment. In contrast, the volumes of the endometrial cysts did not decrease after administration of GnRHa in both groups.. Leuprolide 1.88 induced pituitary down regulation more rapidly than buserelin MP. However the hypoestrogenic symptoms such as hot flashes were more severe in cases treated with leuprolide 1.88 than in those treated with buserelin MP. Our data confirm that the therapeutic efficacy of buserelin MP and leuprolide 1.88 are similar, with both being sufficient to treat uterine leiomyomas and endometriosis.

Topics: Adult; Antineoplastic Agents, Hormonal; Buserelin; Endometriosis; Endometrium; Estradiol; Female; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Hot Flashes; Humans; Leiomyoma; Leuprolide; Luteinizing Hormone; Male; Middle Aged; Ovarian Diseases; Prospective Studies; Treatment Outcome; Ultrasonography; Uterine Diseases; Uterine Hemorrhage

To examine the impact of treating endometriosis with nafarelin or leuprolide acetate depot on patient quality of life (QOL) and subjective clinical measures.. A randomized, multicenter study was conducted on 192 women with endometriosis. Patients received nafarelin or leuprolide for six months and were followed for up to six months after treatment. QOL was defined by seven items, including symptom severity, daily activities, pain medication use and need for bed rest.. No significant differences were found at baseline between treatments for patients with mild, moderate or no endometriosis symptoms. Those with severe symptoms of endometriosis at baseline and taking nafarelin had a significantly greater improvement in QOL at the last posttreatment visit than those receiving leuprolide (P < .01). Nafarelin was associated with significantly fewer days with moderate or severe hot flashes than leuprolide during treatment (P < .05) and with significantly fewer moderate or severe hypoestrogenic symptoms overall at three months of treatment (P < .05). Additionally, poorer QOL was significantly associated with hypoestrogenic and endometriosis symptoms.. Treatment of endometriosis with nafarelin was associated with fewer days of moderate or severe hot flashes as compared to leuprolide and with greater improvement in QOL after treatment in patients with severe symptoms at baseline.

Topics: Adult; Analgesics; Bed Rest; Endometriosis; Female; Fertility Agents, Female; Hormones; Hot Flashes; Humans; Leuprolide; Middle Aged; Nafarelin; Pain; Quality of Life; Severity of Illness Index; Treatment Outcome

The symptoms of women with premenstrual syndrome improve in response to suppression of ovarian function, although these women have no evidence of ovarian dysfunction. We undertook a study to determine the role of estrogen and progesterone in this syndrome.. We first studied the effect of ovarian suppression with leuprolide, an agonist analogue of gonadotropin-releasing hormone, or placebo on symptoms in 20 women with the premenstrual syndrome. Ten women whose symptoms improved during leuprolide treatment were given estradiol and progesterone in a double-blind, crossover design, each for four weeks, during continued leuprolide administration. Women without premenstrual syndrome (normal women) participated in a similar protocol. Outcomes were assessed on the basis of daily self-reports by the patients and biweekly rater-administered symptom-rating scales.. The 10 women with premenstrual syndrome who were given leuprolide had a significant decrease in symptoms as compared with base-line values and with values for the 10 women who were given placebo. The 10 women with premenstrual syndrome who were given leuprolide plus estradiol or progesterone had a significant recurrence of symptoms, but no changes in mood occurred in 15 normal women who received the same regimen or in 5 women with premenstrual syndrome who were given placebo hormone during continued leuprolide administration.. In women with premenstrual syndrome, the occurrence of symptoms represents an abnormal response to normal hormonal changes.

Topics: Adult; Cross-Over Studies; Double-Blind Method; Emotions; Estradiol; Female; Gonadotropin-Releasing Hormone; Hot Flashes; Humans; Leuprolide; Middle Aged; Premenstrual Syndrome; Progesterone

GnRH analogues (GnRH-a) are well established in the treatment of endometriosis. However, due to hypooestrogenic effects, treatment is limited to 6 months. The aim of this randomized, double-blind, comparative study was to evaluate whether symptoms and signs of hypooestrogenism, e.g. hot flushes, sweating and sleeplessness, could be avoided by a steroidal add-back regimen, while the beneficial effect of a GnRH-a on endometriosis could be maintained. In group A, 14 patients were treated with 3.75 mg leuprorelin acetate depot per month i.m. in combination with 20 mg ethinyloestradiol plus 0.15 mg desogestrel orally for 3 weeks. In group P, 13 patients received leuprorelin acetate, following the same schedule as in group A, and placebo. Treatment duration was 6 months. At first-look laparoscopy (postoperatively) group A had an r-AFS score of 23.57 and group P of 24.23. After 6 months of treatment with leuprorelin acetate depot r-AFS scores had dropped to 16.14 in group A and to 6.25 in group P at second-look laparoscopy, achieving statistical significance in both groups (p < 0.001). Hypooestrogenic adverse drug reactions (e.g. hot flushes, sweating and sleeplessness) were more frequently reported in group P, whereas the occurrence of headache was comparable in both groups. Dysmenorrhoea was significantly reduced in both groups, whereas dyspareunia was only decreased in group P. Variations in laboratory values were within normal ranges and did not give any concern about drug safety. Loss of bone mineral density caused by the GnRH-a was reduced by the combined oestrogen/progestin add-back therapy. In conclusion, this therapy can lead to a reduction in hypooestrogenic adverse drug reactions and mostly preserves agonist efficacy with the chance of treatment prolongation.

Topics: Adult; Delayed-Action Preparations; Desogestrel; Double-Blind Method; Endometriosis; Ethinyl Estradiol; Female; Hot Flashes; Humans; Leuprolide; Placebos; Prospective Studies; Sleep Initiation and Maintenance Disorders; Sweating

Topics: Aged; Androgen Antagonists; Anilides; Hot Flashes; Humans; Leuprolide; Male; Mandelic Acids; Muscarinic Antagonists; Nitriles; Prostatic Neoplasms; Tosyl Compounds

While women report sleep interruption secondary to nighttime hot flashes, the sleep disrupting impact of nocturnal hot flashes (HF) is not well characterized. We utilized a model of induced HF to investigate the relationship of nighttime HF to sleep architecture and sleep-stage transitions.. Twenty-eight healthy, premenopausal volunteers received the depot gonadotropin-releasing hormone agonist (GnRHa) leuprolide to rapidly induce menopause, manifesting with HF. Sleep disruption was measured on 2 polysomnograms conducted before and after 4-5 weeks on leuprolide, when HF had developed.. 165 HF episodes were recorded objectively during 48 sleep studies (mean 3.4 HF/night). After standardizing to sleep-stage time distribution, the majority of HF were recorded during wake (51.0%) and stage N1 (18.8%). Sixty-six percent of HF occurred within 5 minutes of an awakening, with 80% occurring just before or during the awakening. Objective HF were not associated with sleep disruption as measured by increased transitions to wake or N1, but self-reported nocturnal HF correlated with an increase from pre- to post-leuprolide in the rate of transitions to wake (p = 0.01), and to N1 (p = 0.008).. By isolating the effect of HF on sleep in women without the confound of age-related sleep changes associated with natural menopause, this experimental model shows that HF arise most commonly during N1 and wake, typically preceding or occurring simultaneously with wake episodes. Perception of HF, but not objective HF, is linked to increased sleep-stage transitions, suggesting that sleep disruption increases awareness of and memory for nighttime HF events.. ClinicalTrials.gov Identifier: NCT01116401.

Topics: Adolescent; Adult; Female; Hot Flashes; Humans; Leuprolide; Menopause; Middle Aged; Polysomnography; Premenopause; Sleep Initiation and Maintenance Disorders; Sleep Stages; Wakefulness; Young Adult

Women are at increased risk for mood disturbance during the menopause transition. Hot flashes (HFs), sleep disruption, and fluctuating estradiol levels correlate with menopause-associated depression but co-occur, making cause and effect relationships difficult to disentangle.. Using a GnRH agonist (GnRHa) experimental model, we investigated whether depressive symptoms are associated with HFs and/or are explained by concomitant sleep fragmentation in the absence of estradiol fluctuation.. Depressive symptoms, objective polysomnographic sleep parameters, subjective sleep quality, serum estradiol, and HFs were assessed before and 4 weeks after open-label depot GnRHa (leuprolide 3.75-mg) administration.. Academic medical center.. Twenty-nine healthy nondepressed premenopausal volunteers (mean age, 27.3 years).. Serum estradiol was rapidly and uniformly suppressed. HFs developed in 69% of the subjects. On univariate analysis, worsening of mood was predicted by increases in time in light sleep (stage N1), number of transitions to wake, non-REM arousals, subjective sleep quality, and reductions in perceived sleep efficiency (all P < .045), as well as the number of nighttime (P = .006), but not daytime (P = .28), HFs reported. In adjusted models, the number of nighttime HFs reported, increases in non-REM arousals, time in stage N1, transitions to wake, and reduced sleep quality remained significant predictors of mood deterioration (P ≤ .05).. Depressive symptoms emerged after estradiol withdrawal in association with objectively and subjectively measured sleep disturbance and the number of nighttime, but not daytime, HFs reported. Results suggest that sleep disruption and perceived nighttime HFs both contribute to vulnerability to menopause-associated depressive symptoms in hypoestrogenic women.

Topics: Adolescent; Adult; Depression; Estradiol; Fertility Agents, Female; Gonadotropin-Releasing Hormone; Healthy Volunteers; Hot Flashes; Humans; Leuprolide; Menopause; Middle Aged; Sleep Wake Disorders; Young Adult

The relationship between depression and estrogen withdrawal remains controversial. The authors examined the effects of gonadotropin-releasing hormone agonist-induced ovarian suppression on mood, sleep, sexual function, and nighttime hot flushes. They focused on whether participating women experienced clinically significant depressive symptoms and whether specific symptoms associated with hypogonadism (nighttime hot flushes and disturbed sleep) increased susceptibility to depression.. Participants were 72 healthy premenopausal women, ages 19-52 years, with no current or past axis I psychiatric diagnosis or gynecological or other medical illness. After 2 months of baseline screening, women received monthly injections of leuprolide acetate (3.75 mg) for 2-3 months. Outcomes were measured using the Beck depression inventory (BDI) and a daily rating scale measuring the severity of several affective and behavioral symptoms. Data were analyzed by repeated-measures analysis of variance using PROC MIXED (for mixed models).. BDI scores ≥10 were reported in four of the 72 women (5.6%). Relative to baseline, induced hypogonadism was associated with significantly decreased sexual interest, disturbed sleep, and more severe nighttime hot flushes, but no significant change in any mood-related symptom score. Hot flush severity was significantly correlated with disturbed sleep.. These data demonstrate that clinically significant depressive symptoms were rare accompaniments of short-term estradiol withdrawal and induced hypogonadism in healthy premenopausal women. Additionally, neither nighttime hot flushes nor disturbed sleep were sufficient to cause depressive symptoms in hypogonadal women.

Topics: Adult; Affect; Depression; Estradiol; Female; Fertility Agents, Female; Hot Flashes; Humans; Hypogonadism; Leuprolide; Middle Aged; Psychiatric Status Rating Scales; Sexual Behavior; Sleep; Women's Health

Sleep interruption is often reported by women with hot flashes and night sweats (or vasomotor symptoms, VMS). Although women report that VMS awaken them, polysomnography (PSG) studies have not consistently supported this contention.. We mimicked menopause using a gonadotropin-releasing hormone agonist (GnRHa) to investigate whether VMS increase awakenings and wake after sleep onset (WASO). VMS, serum estradiol, and at-home PSGs (two pretreatment, two posttreatment) were measured before and after 4 weeks on GnRHa. Regression models were used to determine the effect of increasing VMS frequency on awakenings and WASO, as measured objectively and subjectively.. Twenty-nine healthy women (mean 27.3 y).. Academic medical center.. Depot GnRHa (leuprolide 3.75-mg).. Serum estradiol was rapidly and uniformly suppressed on GnRHa. Persistent VMS were reported by 69% of women. The number of nighttime VMS correlated directly with the degree of sleep disturbance. Each additional reported nighttime VMS was associated with a 62% increase from baseline in PSG-measured WASO (P = 0.007), a 3% increase in awakenings (P = 0.05), and 6% increase in %N1 sleep (P = 0.02). Nighttime VMS were also associated with increased perceived WASO (312%; P = 0.02), awakenings (16%; P = 0.007), Insomnia Severity Index (P = 0.03), and Pittsburgh Sleep Quality Index (P = 0.03) scores, and decreased perceived sleep efficiency (P = 0.01). Objectively recorded nighttime VMS correlated with PSG-measured WASO (rs = 0.45, P = 0.02).. This menopause model demonstrates that nighttime vasomotor symptoms correlate with increased sleep fragmentation. These findings are consistent with a specific contribution of vasomotor symptoms to polysomnography-measured sleep interruption suggesting that nighttime vasomotor symptoms interrupt sleep in the setting of menopause.

Topics: Adolescent; Adult; Circadian Rhythm; Estradiol; Estrone; Female; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Hot Flashes; Humans; Leuprolide; Luteinizing Hormone; Middle Aged; Polysomnography; Sleep; Sleep Wake Disorders; Young Adult

Altered circadian rhythms have been identified in untreated prostate cancer patients. Findings of restored rhythmicity following cancer treatment may have relevance for cancer control and symptom management. This study assessed and compared the cyclic patterns of hot flashes and activity levels in treated prostate cancer patients.. Data were collected during two 24-h periods among 47 prostate patients undergoing androgen deprivation therapy (ADT). Hot flashes were detected objectively through sternal skin conductance and by patients via electronic event marking. Activity levels were recorded on a wrist actigraphy device.. The mean frequency of objectively measured and patient-reported hot flashes was 13.6 (SD = 14.3) and 12.6 (SD = 9.6), respectively. There were significant 24-h circadian rhythms of both hot flashes and activity levels. The peak of the rhythms occurred in early afternoon. There was no significant cross correlation between hot flashes and activity levels.. The acrophases of hot flashes and elevated activity levels in this study may represent a normalisation of circadian rhythms following ADT, pointing to the need for more research, including controlled, prospective chronobiologic studies. Future research may have important implications for the survival of prostate cancer patients and the identification of new and safe hot flash treatments.

Topics: Aged; Aged, 80 and over; Androgen Antagonists; Anilides; Antineoplastic Agents, Hormonal; Circadian Rhythm; Hot Flashes; Humans; Leuprolide; Male; Middle Aged; Motor Activity; Nitriles; Prostatic Neoplasms; Tosyl Compounds

Side effects of cancer treatment have been found to have a significant impact on patients' psychological well-being. Each of the primary treatment options for prostate cancer is associated with significant side effects that can have a dramatic impact on quality of life. Hot flashes are a notable side effect of androgen deprivation therapy (ADT) and a potential source of distress due to their episodic nature and low frequency in a normal aging male population. The current study sought to examine the relationship between hot flashes and cancer-related distress during the first three months of ADT.. Participants were 68 men with various stages of prostate cancer scheduled to begin ADT for the first time. Study measures were completed at the beginning of treatment and 3 months later.. Repeated measures ANOVA indicated that men who did not experience hot flashes had a significant decrease in total cancer-related distress and avoidance over the 3-month period, while men with hot flashes exhibited no change in distress. Among men with hot flashes, results of hierarchical regression analyses indicated that a worse experience with hot flashes was a significant predictor of greater increases in intrusion and total cancer-related distress over the 3-month period.. These results suggest that hot flashes serve to maintain levels of distress during the treatment period. Further research should extend these findings by lengthening the follow-up period and using ecological momentary assessment to refine measurement of these constructs and provide evidence for the direction of causality between hot flashes and distress.

Topics: Adaptation, Psychological; Aged; Aged, 80 and over; Antineoplastic Agents, Hormonal; Chemotherapy, Adjuvant; Combined Modality Therapy; Delayed-Action Preparations; Gonadotropin-Releasing Hormone; Goserelin; Hot Flashes; Humans; Injections, Intramuscular; Leuprolide; Male; Middle Aged; Neoplasm Recurrence, Local; Prostate-Specific Antigen; Prostatic Neoplasms; Quality of Life; Sick Role; Surveys and Questionnaires

To assess the involvement of calcitonin gene-related peptide (CGRP) in the occurrence of hot flashes in men after castration for treatment of prostate cancer, we investigated the effects of CGRP on skin temperature in surgically and medically castrated male rats.. Changes in skin temperature of the hind paws after intravenous injection of 10 microg/kg of CGRP and CGRP family peptides (adrenomedullin and amylin) were measured at 5-minute intervals for 120 minutes, 3 weeks after bilateral orchiectomy or 2 weeks after subcutaneous injection of a gonadotropin-releasing hormone analogue (1.0 mg/kg Leuplin) in male rats. Antagonism with CGRP8-37 (1000 microg/kg intravenously), a CGRP1 receptor antagonist, to the CGRP-induced response was examined by injecting it 10 minutes before injection of CGRP. The effect of testosterone replacement on castration was evaluated in each castrated rat by the administration of testosterone (1.0 mg/kg subcutaneously once a day) for 14 days before the day of the temperature analysis.. CGRP, but not adrenomedullin and amylin, elevated the skin temperature in surgical or medical castration-induced testosterone-deficient rats more than in the sham-treated rats. The difference was statistically significant. The CGRP-induced potentiation in the castrated rats was inhibited by pretreating with CGRP8-37 or by supplying testosterone.. CGRP is the most potent peptide in a family that elevates the skin temperature in male rats. The elevation of the skin temperature was more affected by the testosterone deficiency resulting from castration. These results suggest that CGRP is involved in the mechanism underlying hot flashes in men.

Topics: Adrenomedullin; Amyloid; Animals; Calcitonin Gene-Related Peptide; Gonadotropin-Releasing Hormone; Hindlimb; Hormone Antagonists; Hot Flashes; Injections, Intravenous; Islet Amyloid Polypeptide; Leuprolide; Male; Orchiectomy; Peptide Fragments; Peptides; Rats; Rats, Sprague-Dawley; Receptors, Calcitonin Gene-Related Peptide; Skin Temperature; Testosterone

The therapeutic effects of certain Japanese herbal medicines on menopausal symptoms induced by gonadotropin-releasing hormone agonist therapy were examined in Japanese women with endometriosis, adenomyosis, or leiomyoma. Menopausal symptoms occurred in 17 of the 22 patients. Toki-shakuyaku-san, Shakuyaku-kanzo-to, Keishi-bukuryo-gan, Kami-shoyo-san, Tokaku-joki-to, or Keishi-to was administered to 13 of the 17 patients with menopausal symptoms, and efficacy was observed in all 13. Eleven patients with hot flashes were treated with Toki-shakuyaku-san, and all II patients experienced some relief; four experienced total relief. Three patients complaining of severe shoulder stiffness were treated with Shakuyaku-kanzo-to and were completely relieved of symptoms. There was no significant change in serum estradiol levels after treatment with the Japanese herbal medicines. Our results indicate that Japanese herbal medicines can be recommended for menopausal symptoms induced by gonadotropin-releasing hormone agonists without a negative effect on serum estradiol levels.

Topics: Adult; Endometriosis; Female; Hot Flashes; Humans; Leiomyoma; Leuprolide; Middle Aged; Phytotherapy; Uterine Neoplasms

We sought to determine the prevalence of hot flushes after neoadjuvant hormonal therapy.. Forty-three patients who received neoadjuvant hormonal therapy before radical prostatectomy were asked to complete a questionnaire regarding hot flushes.. Complete information was available for 35 of the 43 patients. No hot flushes were noted in 20%; in 69%, hot flushes were noted during treatment but resolved after termination of treatment; and in 11%, hot flushes continued for at least 3 months after cessation of hormonal therapy. Analyzing the data with respect to duration of hormonal therapy showed that patients receiving neoadjuvant hormonal therapy for more than 4 months had the highest incidence of persistent hot flushes.. Hot flushes will be noted in 80% of patients who receive neoadjuvant hormonal therapy. In approximately 10%, hot flushes will continue for a significant period after hormonal therapy is terminated. Patients should be apprised of this potential side effect.

Topics: Antineoplastic Agents, Hormonal; Chemotherapy, Adjuvant; Flutamide; Hot Flashes; Humans; Leuprolide; Male; Prostatectomy; Prostatic Neoplasms; Surveys and Questionnaires