leuprolide and Amenorrhea

Uterine fibroids are smooth muscle tumours arising from the uterus. These tumours, although benign, are commonly associated with abnormal uterine bleeding, bulk symptoms and reproductive dysfunction. The importance of progesterone in fibroid pathogenesis supports selective progesterone receptor modulators (SPRMs) as effective treatment. Both biochemical and clinical evidence suggests that SPRMs may reduce fibroid growth and ameliorate symptoms. SPRMs can cause unique histological changes to the endometrium that are not related to cancer, are not precancerous and have been found to be benign and reversible. This review summarises randomised trials conducted to evaluate the effectiveness of SPRMs as a class of medication for treatment of individuals with fibroids.. To evaluate the effectiveness and safety of SPRMs for treatment of premenopausal women with uterine fibroids.. We searched the Specialised Register of the Cochrane Gynaecology and Fertility Group, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, PsycINFO, the Cumulative Index to Nursing and Allied Health Literature (CINAHL) and clinical trials registries from database inception to May 2016. We handsearched the reference lists of relevant articles and contacted experts in the field to request additional data.. Included studies were randomised controlled trials (RCTs) of premenopausal women with fibroids who were treated for at least three months with a SPRM.. Two review authors independently reviewed all eligible studies identified by the search. We extracted data and assessed risk of bias independently using standard forms. We analysed data using mean differences (MDs) or standardised mean differences (SMDs) for continuous data and odds ratios (ORs) for dichotomous data. We performed meta-analyses using the random-effects model. Our primary outcome was change in fibroid-related symptoms.. We included in the review 14 RCTs with a total of 1215 study participants. We could not extract complete data from three studies. We included in the meta-analysis 11 studies involving 1021 study participants: 685 received SPRMs and 336 were given a control intervention (placebo or leuprolide). Investigators evaluated three SPRMs: mifepristone (five studies), ulipristal acetate (four studies) and asoprisnil (two studies). The primary outcome was change in fibroid-related symptoms (symptom severity, health-related quality of life, abnormal uterine bleeding, pelvic pain). Adverse event reporting in the included studies was limited to SPRM-associated endometrial changes. More than half (8/14) of these studies were at low risk of bias in all domains. The most common limitation of the other studies was poor reporting of methods. The main limitation for the overall quality of evidence was potential publication bias. SPRM versus placebo SPRM treatment resulted in improvements in fibroid symptom severity (MD -20.04 points, 95% confidence interval (CI) -26.63 to -13.46; four RCTs, 171 women, I. Short-term use of SPRMs resulted in improved quality of life, reduced menstrual bleeding and higher rates of amenorrhoea than were seen with placebo. Thus, SPRMs may provide effective treatment for women with symptomatic fibroids. Evidence derived from one RCT showed no difference between leuprolide acetate and SPRM with respect to improved quality of life and bleeding symptoms. Evidence was insufficient to show whether effectiveness was different between SPRMs and leuprolide. Investigators more frequently observed SPRM-associated endometrial changes in women treated with SPRMs than in those treated with placebo or leuprolide acetate. As noted above, SPRM-associated endometrial changes are benign, are not related to cancer and are not precancerous. Reporting bias may impact the conclusion of this meta-analysis. Well-designed RCTs comparing SPRMs versus other treatments are needed.

Topics: Amenorrhea; Antineoplastic Agents, Hormonal; Estrenes; Female; Humans; Leiomyoma; Leuprolide; Menstruation; Mifepristone; Norpregnadienes; Oximes; Pelvic Pain; Quality of Life; Randomized Controlled Trials as Topic; Receptors, Progesterone; Uterine Neoplasms

Topics: Amenorrhea; Bone Density; Cyclophosphamide; Female; Gonadotropin-Releasing Hormone; Humans; Leuprolide; Ovary

To evaluate the efficacy and safety of ulipristal acetate (UPA) for uterine fibroids (UFs), a phase III study was conducted with leuprorelin (LEU) as a comparator. This is the first confirmatory trial of UPA for UFs among Asians.. Multicenter, randomized, double-blind, double-dummy, parallel-group study.. Thirty-two sites in Japan.. Patients were assigned to 2 arms, with 82 patients in the UPA group and 79 patients in the LEU group.. In the UPA group, 10 mg of UPA was orally administered once a day for 12 weeks. In the LEU group, 1.88 mg or 3.75 mg of LEU was subcutaneously administered at weeks 0, 4, and 8.. The primary endpoint was the percentage of patients with amenorrhea for 35 days. For safety evaluation, adverse events (AEs) were recorded.. The percentage of patients with amenorrhea for 35 days was 87.0% in the UPA group and 81.8% in the LEU group, and the efficacy of UPA for causing amenorrhea for 35 days was confirmed to be noninferior to that of LEU. AEs occurred in 78.0% of the patients in the UPA group and 88.8% of the patients in the LEU group.. The effect of UPA on heavy menstrual bleeding was shown to be comparable with that of LEU in Japanese patients with symptomatic UFs. No notable AEs occurred because of the UPA treatment, and the incidence of AEs in the UPA group was comparable with that of AEs in the LEU group. This result demonstrates the clinical utility of UPA for Asians.

Topics: Adult; Amenorrhea; Double-Blind Method; Female; Humans; Japan; Leiomyoma; Leuprolide; Menorrhagia; Middle Aged; Norpregnadienes; Time Factors; Treatment Outcome; Uterine Neoplasms

To evaluate the efficacy and safety of 10 mg and 25 mg mifepristone per day compared with 3.75 mg enantone in treating uterine fibroids.. This is a Multicenter randomized controlled trial. A total of 501 subjects with symptomatic uterine fibroids were enrolled and randomized into the group of 10mg, 25mg mifepristone and 3.75 enantone (with 307, 102 and 92 subjects respectively), with 458 subjects completed the treatment. Three months of daily therapy with oral mifepristone (at a dose of either 10 mg or 25 mg) or once-monthly subcutaneous injections of enantone (at a dose of 3.75 mg) were used. Change in volume of the largest uterine fibroid was the primary efficacy variable, and secondary efficacy variables included changes in anemia and relevant symptom. Safety evaluation included the analyses of adverse events, laboratory values, and relevant endometrial changes.. After three months of treatment, the mean volume of the largest leiomyoma was significantly reduced by mifepristone 10 mg or 25 mg or enantone 3.75 mg (40.27%, 42.59% and 44.49% respectively) (P < 0.0001). Percentage change from baseline in largest leiomyoma volume was not statistically significant among the three groups (P = 0.1057). Most of the patients in all groups experienced amenorrhea after the treatment. There were also significant elevations in red blood cell count, hemoglobin and hematocrit (P < 0.0001), and significant reductions in prevalence of dysmenorrhea, pelvic pressure, non-menstrual abdominal pain (P < 0.0001) in each group, while no significant difference among the three groups.All study medications are well-tolerated, and no serious adverse event was reported. Treatment-related adverse event rate was significantly lower in mifepristone 10 mg group, compared to Enantone 3.75 mg group (13.59% vs. 32.58%, P = 0.0002). In both mifepristone groups, estradiol levels were maintained in the premenopausal range, whereas patients in the enantone group had a significant reduction to postmenopausal levels (P < 0.0001).. 10mg is as effective as 25mg mifepristone and 3.75 mg enantone with minimal drug-related side effects, and may provide an alternative for clinical application, especially for patient who are in perimenopause with uterine fibroids.

Topics: Adult; Amenorrhea; Antineoplastic Agents, Hormonal; Dose-Response Relationship, Drug; Dysmenorrhea; Female; Hematologic Tests; Hormone Antagonists; Humans; Leiomyoma; Leuprolide; Middle Aged; Mifepristone

Hyperandrogenism is a relatively common clinical problem. However, severe hyperandrogenism causing virilisation is rare. A 27-year-old woman presented with generalised hirsutism, clitoromegaly, breast atrophy and secondary amenorrhoea. She had serum testosterone levels elevated to the adult male range. Administration of gonadotropin-releasing hormone (GnRH) analogue resulted in >50% suppression of serum testosterone which was suggestive of luteinising hormone-dependent ovarian hyperandrogenism. Imaging studies of abdomen and pelvis were normal, and ovarian venous sampling failed to show a gradient between the two sides. A presumptive diagnosis of ovarian hyperthecosis was, therefore, considered. Medical treatment with GnRH analogue and combined oral contraceptive pills was initiated to which an excellent clinical and biochemical response was noted. This case highlights a rare presentation of ovarian hyperthecosis in a young woman with severe hyperandrogenism mimicking a virilising neoplasm.

Topics: Adult; Amenorrhea; Contraceptives, Oral; Female; Humans; Hyperandrogenism; Hyperplasia; Leuprolide; Testosterone; Theca Cells; Treatment Outcome

To describe the rates of use and effectiveness of gonadotropin-releasing hormone (GnRH) agonists and other forms of hormonal menstrual suppression in prevention of vaginal bleeding among young women who underwent hematopoietic stem cell transplantation (HCT).. Retrospective descriptive study.. University-based pediatric HCT practice.. Fifty-five postmenarchal women who underwent HCT between 2004 and 2011.. Administration of GnRH agonists or other forms of hormonal menstrual suppression.. Rates of use of GnRH agonists and other forms of hormonal menstrual suppression, and rates and descriptions of vaginal bleeding.. Forty-six of the 55 patients had experienced regular or irregular vaginal bleeding before HCT and were considered to be at risk for thrombocytopenia-associated menorrhagia. Forty of the 46 (87%) received hormonal menstrual suppression. Thirty-three patients were treated with a GnRH agonist, 4 with combined hormonal contraceptive pills, 1 with a combined hormonal contraceptive patch, 1 with depot medroxyprogesterone, and 1 with oral norethindrone. Twenty-nine of the 33 patients (88%) who received a GnRH agonist had complete amenorrhea during HCT and 4 of 33 (12%) experienced some degree of vaginal bleeding.. GnRH agonists appear effective in prevention of vaginal bleeding complications in most postmenarchal women who underwent HCT. Some patients who might benefit do not receive a GnRH agonist and multiple barriers exist in identification and treatment of them.

Topics: Adolescent; Adult; Amenorrhea; Child; Contraceptive Agents, Female; Female; Gonadotropin-Releasing Hormone; Goserelin; Hematopoietic Stem Cell Transplantation; Humans; Leuprolide; Preoperative Care; Retrospective Studies; Treatment Outcome; Uterine Hemorrhage; Young Adult

To examine the interaction between circulating beta-endorphin levels and sex steroids during sustained submaximal exercise in runners who are either anovulatory and oligomenorrheic (AO) or ovulatory and eumenorrheic (EO).. Controlled clinical study.. General clinical research center at an academic medical center.. Three AO and four EO runners.. The athletes underwent 60 minutes of submaximal treadmill exercise on three separate occasions. Anovulatory and oligomenorrheic runners underwent exercise at baseline and after physiologic estrogen and combined estrogen and progesterone replacement. Ovulatory and eumenorrheic runners underwent exercise in the follicular and luteal phases and after GnRH agonist desensitization.. Serum cortisol, beta-endorphin, progesterone, estrogen, and gonadotropin levels at rest and during exercise.. Serum levels of E2 increased in response to exercise in both EO and AO runners during sex steroid replacement. Baseline peripheral beta-endorphin and cortisol levels were not different between the EO and AO groups. A significant increase in beta-endorphin levels in response to exercise occurred only in the EO group after GnRH agonist desensitization.. Alterations in menstrual cyclicity and ovulation in conditioned runners probably are not due to an increase in opioid tone. The hypothalamic-gonadotropic axis appears to be intact in AO runners, as measured by the gonadotropic response to exogenous exposure to estrogen and progesterone. Sex steroid administration had no effect on basal beta-endorphin levels, but this probably was not due to preexisting increased opioid tone.

Topics: Adult; Amenorrhea; Anovulation; beta-Endorphin; Estradiol; Estrogens; Exercise; Female; Follicle Stimulating Hormone; Gonadal Steroid Hormones; Humans; Hydrocortisone; Kinetics; Leuprolide; Menstrual Cycle; Progesterone; Rest; Running

To describe the efficacy of mifepristone in the prevention of menstrual bleeding and ovulation, with similar observations in comparison groups.. Prospective experimental study. Thirty-two cynomolgus monkeys were divided equally into four treatment groups (n = 8). Treatment lasted for 1 year.. Group I received GnRH-agonist (GnRH-a) and in-sequence mifepristone, group II received mifepristone only, group III received GnRH-a only, and group IV received vehicle control.. Serum estradiol and progesterone, menstrual bleeding, endometrial thickness, and endometrial expression of basic fibroblast growth factor (bFGF) as determined by immunohistochemistry.. Weekly progesterone determinations showed that mifepristone-treated monkeys seldom ovulated (6 ovulations in 8 years), compared with the controls (100 ovulations in 8 years), while maintaining early to midfollicular levels of circulating serum estradiol. The GnRH-a-only group also rarely ovulated, but was chronically and severely hypoestrogenic. The mifepristone-only group showed scant menstrual bleeding (5 days in 8 years) as compared with the menstrual frequency in control animals (422 days in 8 years). Endometrial proliferation, as determined by biopsy, was similarly minimal for both the GnRH-a and mifepristone groups, and statistically less than in control monkeys. Both the mifepristone and GnRH-a treatments suppressed endometrial gland expression of the angiogenesis polypeptide bFGF.. Chronic mifepristone induced anovulation along with virtual amenorrhea, which suggests the worth of this novel hormonal contraceptive.

Topics: Amenorrhea; Animals; Contraception; Endometrium; Female; Fibroblast Growth Factor 2; Hormone Antagonists; Leuprolide; Macaca fascicularis; Mifepristone; Ovulation

To evaluate the prevalence of resumption of menstruation after an interval of amenorrhea in women treated by endometrial ablation and myometrial resection.. Retrospective analysis.. Tertiary care university-affiliated teaching hospital.. One hundred fifty-seven consecutive patients treated for menorrhagia refractory to medical therapy.. Loop resection or rollerball ablation of the endometrium.. At 6 to 12 months postoperatively, 50. 6% of patients were amenorrheic and 35.1% had hypomenorrhea. Over follow-up of 13 to 30 months, 45.1% of women became amenorheic and 40.5% had satisfactory hypomenorrhea. Resumption of menstruation after any interval of amenorrhea occurred in 27.2% of amenorheic patients. We observed an increasing trend to resumption of menstruation after rollerball ablation (29.4%) compared with loop resection (26.7%) and after preoperative endometrial suppression with buserelin (37.5%) and leuprolide (27.1%) compared with danazol (12.5%) and goserelin (10.5%). Resumption of menstruation occurred in 44.4% of women who did not have preoperative endometrial suppression.. Our results suggest that resumption of menstruation does occur after a variable interval of amenorrhea following endometrial ablation and myometrial resection. It could potentially be used as a marker of failure of endometrial destruction.

Topics: Amenorrhea; Buserelin; Danazol; Electrocoagulation; Endometrium; Female; Follow-Up Studies; Goserelin; Humans; Leuprolide; Menorrhagia; Myometrium; Postoperative Complications; Preoperative Care; Retrospective Studies; Time Factors; Treatment Failure

To evaluate, in a pilot study, the use and efficacy of a gonadotropin-releasing hormone (GnRH)-agonist in inducing amenorrhea in women undergoing BMT.. We evaluated the use of the GnRH agonist leuprolide acetate (LA) for the induction of amenorrhea in 10 postmenarcheal women prior to BMT. If there was a contraindication to the use of the intramuscular (i.m.) formulation of LA, the subcutaneous (s.c.) formulation was given as a daily intravenous (i.v.) bolus. Once the subject's platelet count was > 50,000/microL, the LA was discontinued. Menstrual bleeding, time from initiation of therapy to amenorrhea, and liver function test results were monitored.. All subjects had induction of amenorrhea with the use of LA except for one subject with a large, myomatous uterus, who experienced light spotting. One subject who was thrombocytopenic at the prescribed time of the second dosage of i.m. LA received i.v. LA with documentation of continued pituitary/gonadal suppression. No adverse effects were determined to be directly related to either the i.m. or i.v. LA.. LA is an option for the induction of amenorrhea in postmenarcheal women undergoing BMT. In thrombocytopenic subjects, administration of the s.c. formulation of LA by an i.v. route served as an alternative to i.m. injection and was documented to maintain gonadotropin suppression.

Topics: Adolescent; Adult; Amenorrhea; Bone Marrow Transplantation; Contraindications; Female; Humans; Injections, Intramuscular; Injections, Intravenous; Leukemia; Leuprolide; Lymphoma; Pilot Projects; Platelet Count; Uterine Hemorrhage

The gynecologic resectoscope, recently approved by the Food and Drug Administration for the treatment of abnormal uterine bleeding, was evaluated for its success in the treatment of women with this complaint. Through June 1990, 216 patients were treated with this modality. Ninety were treated with transcervical myomectomy alone since they still desired fertility preservation or wished to avoid hysterectomy. Of the patients treated, 189 (87.5%) had follow-up evaluation for at least three months and some as long as three years. Of the ninety patients treated with resection of a submucous myoma, greater than 90% had a marked improvement in their symptoms, with decreased menstrual bleeding. Of the 96 patients treated with endometrial ablation, 50% were amenorrheic, 26% had hypomenorrhea, 17% had eumenorrhea, and 7% were unimproved. There was only one case of fluid overload, and no patients required a blood transfusion. Complications included two cases of endometritis and one perforation at the time of retrieval of myoma fragments. Four patients required placement of a 30-mL Foley catheter for control of postoperative bleeding. Gynecologic resectoscopy is a safe and effective alternative to major surgery in the management of abnormal uterine bleeding for which conservative measures have not been effective.

Topics: Adult; Aged; Amenorrhea; Antineoplastic Agents; Catheterization; Danazol; Electrocoagulation; Endometrium; Female; Humans; Hysteroscopes; Leiomyoma; Leuprolide; Medroxyprogesterone; Medroxyprogesterone Acetate; Menstruation Disturbances; Middle Aged; Uterine Neoplasms; Uterus

The efficacy of a technique of gonadotropin suppression and human menopausal gonadotropins (hMG) to induce ovulation in women with hypergonadotropic amenorrhea was evaluated in 100 consecutive women. Ovulation was achieved in 19% of cycles (68/361), the pregnancy rate per cycle was 5.2% (19/361), and the viable pregnancy rate was 2.2% (8/361). In the majority of the successful cases, estrogen was used to decrease the elevated luteinizing hormone and follicle-stimulating hormone levels, especially where the ethinyl estradiol therapy alone induced a rise in endogenous 17 beta-estradiol levels with hMG used to boost the follicle to maturation. Although the success rate is low, this technique can result in some successes in otherwise almost hopeless cases.

Topics: Adult; Amenorrhea; Estrogens; Ethinyl Estradiol; Female; Gonadotropin-Releasing Hormone; Gonadotropins; Hormones; Humans; Infertility; Leuprolide; Menotropins; Middle Aged; Ovulation Induction; Pregnancy; Pregnancy Outcome; Time Factors

A highly potent analogue of OH-RH, d-Leu6 des GLY10 LH-RH-ethyl-amide was, used to study gonadotropin release after three repeated injections of a 25-microgram dose at 3-hourly intervals. Nine volunteers at different stages of the menstrual cycle and 14 patients with functional hypothalamic amenorrhea were investigated. LH secretion varied greatly according to the functional state of the gonadostats, whereas FSH release did not show such differences. After repeated stimulation with the analogue, a tendency for diminished release of both gonadotropins was observed. Significant incremental changes of estradiol-17 beta levels occurred only after a decrease of pituitary responsiveness to further d-Leu6 des Gly10 LH-RH-EA stimuli was already evident. Therefore, it appears unlikely that estradiol-17 beta itself exerted a substantial negative feedback action on LH and FSH release in our experimental model. It is suggested that repeated administration of d-Leu6 des Gly 10 LH-RH-EA leads to changes of pituitary receptor sensitivity.

Topics: Amenorrhea; Estradiol; Female; Follicle Stimulating Hormone; Follicular Phase; Gonadotropin-Releasing Hormone; Humans; Leuprolide; Luteal Phase; Luteinizing Hormone; Menstruation