leuprolide and tibolone

Topics: Antineoplastic Agents, Hormonal; Diagnosis, Differential; Drug Therapy, Combination; Estrogen Receptor Modulators; Female; Gynecologic Surgical Procedures; Humans; Laparoscopy; Leiomyoma; Leiomyomatosis; Leuprolide; Norpregnenes; Prognosis; Randomized Controlled Trials as Topic; Risk Factors; Uterine Neoplasms

To investigate the effects of tibolone co-administration with GnRH agonist treatment in terms of cognition, mood, and quality of life.. Randomized, controlled, single-blind, clinical trial.. Department of gynecology and obstetrics at a university in Italy.. One hundred ten premenopausal women with symptomatic uterine leiomyomas.. Six months of treatment with leuprolide acetate depot (11.25 mg IM, every 3 mo) associated with either tibolone (2.5 mg/d orally; group A) or placebo (1 tablet per d; group B).. At baseline and after 6 months of treatment, uterine and leiomyoma sizes, leiomyoma-related symptoms, climacteric-like symptoms, cognition, mood, and quality of life.. At study entry, no difference was detected between groups in any parameters assessed. After treatment, the leiomyoma-related symptoms were significantly reduced in both groups, without any statistically significant differences between them. The Kupperman Index was statistically significantly higher in group B in comparison with baseline and group A. The cognition scores were statistically significantly different in comparison with baseline in group B, whereas no change was observed in group A. After treatment, mood and quality of life were statistically significantly improved in both groups, even though the improvement was significantly higher in group A than in group B.. Tibolone administration reverses the deleterious effect on cognition that is caused by leuprolide acetate depot and improves mood and quality of life in patients who receive GnRH agonist for symptomatic uterine leiomyomas.

Topics: Administration, Oral; Adult; Affect; Antineoplastic Agents, Hormonal; Central Nervous System Agents; Cognition; Delayed-Action Preparations; Female; Humans; Leiomyoma; Leuprolide; Middle Aged; Norpregnenes; Quality of Life; Single-Blind Method; Time Factors; Treatment Outcome; Uterine Neoplasms

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

To evaluate the effectiveness of gonadotropin-releasing hormone agonists (GnRH-a) with or without coadministration of tibolone in women with menstrual cycle-related irritable bowel syndrome (IBS).. Prospective, randomized, placebo-controlled clinical trial.. Universities of Catanzaro and Naples.. One hundred twenty young premenopausal women with menstrual cycle-related IBS (Rome II criteria).. Administration of leuprolide acetate depot (LAD, 11.25 mg IM/3 months) plus tibolone (group A), LAD plus placebo tablets (group B), and injection of a placebo solution plus placebo tablets (group C).. Severity of bowel symptoms or signs of IBS and quality of life (QoL), at baseline and after 6 months of treatment.. In all groups, the mean scores for each symptom or sign of IBS and for QoL were significantly improved after treatment. A significant difference was observed between group C and groups A and B. No difference between these last groups was detected in symptoms or signs of IBS. The QoL scores were significantly higher in group A than in group B.. Gondotropin-releasing hormone agonist administration is effective in women with menstrual cycle-related IBS. The addition of tibolone does not reduce effectiveness compared with agonist alone and increases QoL.

Topics: Adult; Antineoplastic Agents, Hormonal; Drug Therapy, Combination; Female; Humans; Irritable Bowel Syndrome; Leuprolide; Menstrual Cycle; Norpregnenes; Patient Dropouts; Premenopause; Quality of Life; Treatment Outcome

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Female; Humans; Immunohistochemistry; Leiomyoma; Leuprolide; Norpregnenes; Proliferating Cell Nuclear Antigen; Proto-Oncogene Proteins c-bcl-2; Uterine Neoplasms

To investigate the response of the various hyperplastic disorders of the endometrium to a prolonged treatment with leuprolide acetate, a gonadotropin-releasing hormone agonist (GnRH-a), plus tibolone, as add-back therapy, and further to study if the tibolone addition reduces the hypoestrogenic actions of the GnRH-analogue.. We treated 26 women with histologically confirmed simple (n = 9), complex (n = 15) or atypical (n = 2) endometrial hyperplasia (EH) for 12 months with monthly injections of 1Ampulle/3.75 mg of leuprolide acetate, followed by tibolone, 2.5mg per day per os. Every woman underwent a hysteroscopic evaluation and biopsy of the endometrium after 3 (in cases with atypical EH), 6 and 12 months of treatment, as well as after 12 and 24 months of follow-up. The clinical, paraclinical and laboratory course of the disease was followed-up by using of a climacteric scoring system and by testing of various parameters.. The histopathologic evaluation of the endometria revealed regression of EH in all women after 12 months of treatment, however, during the first 2 years of follow-up EH reappeared in four women (4/21, 19%). Bone mineral density and serum parameters did not show significant changes during treatment, whereas only a mild suffering from hypoestrogenic side-effects was noted.. It seems that the combined GnRH-a/tibolone treatment in women with EH is a potent alternative, so far as the endometrial status and the clinical course of the disease are concerned, whereas tibolone appears to act sufficiently as add-back therapy to prolonged GnRH-a treatment. The probability of relapse of the disease during the follow-up period makes the close monitoring of the endometrium after cessation of the treatment absolutely necessary.

Topics: Adult; Drug Therapy, Combination; Endometrial Hyperplasia; Estrogen Receptor Modulators; Female; Gonadotropin-Releasing Hormone; Humans; Injections; Leuprolide; Middle Aged; Norpregnenes; Treatment Outcome

Leptin seems to regulate reproductive function and it has been hypothesised that its secretion may be induced by oestrogens. Changes in its levels has been advocated as a determinant in the pathogenesis of premenstrual syndrome (PMS). We evaluated serum leptin levels in patients affected by PMS and in controls to establish: (i) if induced hypoestrogenism has an impact on leptin concentrations; (ii) if the administration of tibolone modifies the effects of hypoestrogenism on serum leptin levels; and (iii) if the improvement in PMS symptomatology can be correlated to changes in serum leptin levels.. Prospective, randomized study.. Twenty-eight women affected by PMS and 20 unaffected controls. Affected patients were randomly assigned to two groups to receive leuprolide acetate (3.75 mg intramuscularly) plus tibolone (2.5 mg/day) (group A; n = 14) or plus placebo (group B; n = 14), at the onset of the vasomotor symptoms.. Serum leptin, oestradiol and progesterone levels, PMS signs and symptoms evaluated during a 2 months' pretreament period and after 2 months of therapy.. No differences in leptin levels among the three groups and within the same group at all time evaluated were observed. Oestradiol and progesterone concentrations were significantly lower in all groups during treatment in comparison with pretreatment values. Before therapy, leptin levels were positively correlated both with oestradiol and progesterone in the follicular and luteal phase in all groups. This correlation was lost after treatment. All PMS patients showed a significant improvement of the symptomatology.. Hypoestrogenism induced by GnRH analogues (GnRHa) does not seem to influence leptin levels in normal women and those with PMS, and the addition of tibolone does not impact on these levels. Because PMS symptomatology did significantly improve during treatment with GnRHa alone, or in associtation with tibolone, it is unlikely that changes in leptin levels could have an important role in the pathophysiology of PMS.

Topics: Adult; Androgen Antagonists; Case-Control Studies; Estradiol; Female; Fertility Agents; Humans; Leptin; Leuprolide; Menstrual Cycle; Norpregnenes; Premenstrual Syndrome; Progesterone; Prospective Studies; Treatment Outcome

To study the bone metabolism in postmenopausal women who have been treated with gonadotropin-releasing hormone agonist (GnRH-a) and tibolone.. Prospective, open, controlled clinical trial.. Department of Gynecology and Obstetrics, University of Catanzaro, Catanzaro, Italy.. One hundred twenty perimenopausal women with symptomatic uterine leiomyomas (groups A and B), and 40 healthy control women who underwent a normal spontaneous menopause (group C).. Treatment for 12 months with leuprolide acetate plus tibolone (group A) or hysterectomy with bilateral oophorectomy (group B).. Lumbar spine bone mineral density (BMD) and bone turnover markers at entry into the study, after medical treatment (only group A), and 12 months after discontinuation medical treatment (group A) or after surgery (group B). The same parameters were noted in healthy women before and 12 months after menopause (retrospective control group, group C).. At the women's entry into the study, no significant difference in BMD and bone turnover markers was detected between groups A and B. In group A, no significant variation in BMD or bone turnover markers was observed 12 months after medical treatment in comparison with baseline. At 12 months after discontinuation of treatment (in women who had achieved menopause) and after surgery, we observed a statistically significant decrease in BMD and in bone turnover markers in both groups in comparison with baseline. At 12 months after they became menopausal, we also observed a statistically significant reduction in BMD and in bone turnover markers in control group C. At the same 12-month follow-up visit, a statistically significant difference in BMD and in bone turnover markers was detected when comparing groups A and B with group C.. Women previously treated with GnRH-a and tibolone similar to women who are menopausal as a result of surgery, have higher bone loss after menopause.

Topics: Antineoplastic Agents, Hormonal; Antineoplastic Combined Chemotherapy Protocols; Bone and Bones; Bone Density; Bone Development; Female; Gonadotropin-Releasing Hormone; Humans; Hysterectomy; Leiomyoma; Leuprolide; Lumbar Vertebrae; Middle Aged; Norpregnenes; Osteoporosis, Postmenopausal; Ovariectomy; Postmenopause; Prospective Studies; Reference Values; 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

To evaluate the efficacy and tolerability of a low-dose estrogen-only regimen as a short-term add-back therapy during post-operative GnRH agonist (GnRHa) treatment of patients with endometriosis.. Retrospective cohort study. One hundred seventeen women of reproductive age who were treated with post-operative GnRHa after conservative laparoscopic surgery for endometrioma were eligible for this study. The patients were divided into two groups: group A (n = 56) received tibolone (2.5mg) between 2002 and 2004 and group B (n = 61) received estradiol valerate (1mg) between 2005 and 2007 as an add-back therapy for five months, beginning at the time of the second injection of a GnRHa. The incidence of hypoestrogenic symptoms and the degree of pelvic pain according to a verbal rating scale (VRS) scoring system, the incidence and patterns of uterine bleeding during add-back therapy, the endometrial thickness by ultrasonography two months after the last GnRHa treatment, and the serum CA-125 level were evaluated.. The incidence of uterine bleeding, hypoestrogenic symptoms such as hot flashes and sweating, and pelvic pain did not differ significantly between the two treatment groups. However, the endometrium was thicker in group A than group B (p = 0.022). In group B, the frequency of uterine bleeding was lower from the second month after starting add-back therapy than in group A, but without statistical significance (at the sixth month, p = 0.086).. The low-dose estrogen-only regimen was efficacious and tolerable as a short-term add-back therapy during post-operative GnRHa treatment after surgery for endometriosis.

Topics: Adult; Cohort Studies; Endometriosis; Endometrium; Estradiol; Estrogens; Female; Gonadotropin-Releasing Hormone; Humans; Leuprolide; Norpregnenes; Pelvic Pain; Ultrasonography

The natural history and the factors that lead to the acquisition of atypia in endometrial hyperplasias in young aged women, especially under the age of 20, have not been fully elucidated. In such cases, although there exists a considerable risk of progression to carcinoma, a conservative antiestrogenic treatment is primarily indicated, in attempt to preserve the reproductive ability of the young woman. We report of a 18-year-old girl with atypical hyperplasia of the endometrium, a diagnosis confirmed by reviewing of the histologic material by specialized gynecopathologists. The patient has been treated with gonadotropin releasing hormone agonist (leuprolide acetate) and tibolone for 1 year, which led to endometrial atrophy and amenorrhea, without hypoestrogenic side effects. Six months after cessation of the therapy the endometrial hyperplasia relapsed (this time without atypia), but in about 2 years of follow-up and after short courses of treatment with clomiphene citrate and progestins the biopsy of the endometrium revealed a functional endometrium and the patient presents with an almost regular menstrual cycle.

Topics: Adolescent; Clomiphene; Diagnosis, Differential; Endometrial Hyperplasia; Female; Humans; Leuprolide; Neoplasm Recurrence, Local; Norpregnenes; Precancerous Conditions; Progestins; Ultrasonography

Topics: Drug Therapy, Combination; Female; Gonadotropin-Releasing Hormone; Humans; Leuprolide; Norpregnenes; Premenstrual Syndrome