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1.
Fertil Steril ; 95(5): 1720-4.e1-8, 2011 Apr.
Article in English | MEDLINE | ID: mdl-21300344

ABSTRACT

OBJECTIVE: To determine an effective multiple-dose regimen of anastrozole compared with clomiphene citrate (CC) to induce follicular growth and ovulation in infertile women with ovulatory dysfunction. DESIGN: Phase II, prospective, randomized, double-blind, multicenter, dose-finding, noninferiority study. SETTING: Outpatient. PATIENT(S): Infertile women (n = 271) with ovulatory dysfunction, aged 18-40 years, with body mass index <37 kg/m(2). INTERVENTION(S): Five days of anastrozole at 1, 5, or 10 mg/d or CC at 50 mg/d. MAIN OUTCOME MEASURE(S): The primary endpoint was the ovulation rate (mid-luteal phase serum P level ≥ 10 ng/mL or clinical pregnancy) in the first treatment cycle (cycle 1). RESULT(S): In cycle 1 the ovulation rates for anastrozole at 1, 5, and 10 mg/d were 30.4% (n = 24), 36.8% (n = 28), and 35.9% (n = 14), respectively, compared with 64.9% (n = 50) for CC at 50 mg/d. In up to three cycles of treatment, cumulative ovulation rates did not differ between groups. No cases of ovarian hyperstimulation syndrome were reported, and both anastrozole and CC were well tolerated. CONCLUSION(S): In terms of ovulation rates, 5-day anastrozole at 1, 5, and 10 mg/d was less effective than CC at 50 mg/d for cycle 1 (noninferiority was not shown).


Subject(s)
Clomiphene/therapeutic use , Infertility, Female/therapy , Nitriles/therapeutic use , Ovulation Induction/methods , Triazoles/therapeutic use , Adolescent , Adult , Anastrozole , Clomiphene/administration & dosage , Clomiphene/adverse effects , Dose-Response Relationship, Drug , Double-Blind Method , Female , Fertility Agents, Female/administration & dosage , Fertility Agents, Female/adverse effects , Fertility Agents, Female/therapeutic use , Humans , Infertility, Female/physiopathology , Nitriles/administration & dosage , Nitriles/adverse effects , Ovarian Hyperstimulation Syndrome/epidemiology , Ovarian Hyperstimulation Syndrome/etiology , Ovulation/drug effects , Ovulation/physiology , Ovulation Induction/adverse effects , Pregnancy , Pregnancy Rate , Triazoles/administration & dosage , Triazoles/adverse effects , Young Adult
2.
Fertil Steril ; 95(5): 1725-9.e1-8, 2011 Apr.
Article in English | MEDLINE | ID: mdl-21316048

ABSTRACT

OBJECTIVE: To compare the effects of anastrozole and clomiphene citrate (CC) on follicular development and ovulation in infertile women with ovulatory dysfunction. DESIGN: Phase II, prospective, randomized, assessor-blind, multicenter, dose-finding, noninferiority study. SETTING: Outpatient. PATIENT(S): Infertile women with ovulatory dysfunction, aged 18-35 years, and body mass index <35 kg/m(2). INTERVENTION(S): Single-dose anastrozole at 5 mg (n = 39), 10 mg (n = 39), 20 mg (n = 39), or 30 mg (n = 38) or a 5-day course of CC at 50 mg/d (n = 39) as starting doses. MAIN OUTCOME MEASURE(S): The primary endpoint was the ovulation rate in the first treatment cycle (cycle 1). Ovulation was defined as a midluteal phase serum P level ≥ 10 ng/mL or clinical pregnancy. RESULT(S): In cycle 1 the ovulation rates for a single dose of anastrozole at 5, 10, 20, and 30 mg were 46.2%, 41.0%, 23.1%, and 28.9%, respectively, whereas that for CC at 50 mg/d was 61.5%. Among women with fewer than six menses per year, the cumulative ovulation rates over three cycles were comparable in the anastrozole 5 mg (52.4%) and CC 50 mg/d (42.3%) groups. CONCLUSION(S): In terms of ovulation rates in cycle 1, single-dose anastrozole at 5, 10, 20, and 30 mg was not as effective as CC at 50 mg/d for 5 days (noninferiority was not shown).


Subject(s)
Anovulation/drug therapy , Infertility, Female/drug therapy , Nitriles/administration & dosage , Triazoles/administration & dosage , Adolescent , Adult , Anastrozole , Anovulation/complications , Clomiphene/administration & dosage , Clomiphene/adverse effects , Dose-Response Relationship, Drug , Female , Fertility Agents, Female/administration & dosage , Fertility Agents, Female/adverse effects , Humans , Infertility, Female/etiology , Nitriles/adverse effects , Ovulation Induction/adverse effects , Ovulation Induction/methods , Pregnancy , Pregnancy Rate , Single-Blind Method , Triazoles/adverse effects , Young Adult
3.
Curr Med Res Opin ; 24(10): 2785-93, 2008 Oct.
Article in English | MEDLINE | ID: mdl-18727841

ABSTRACT

OBJECTIVE: To assess the requirement for luteinizing hormone (LH) in women deficient in LH and follicle-stimulating hormone (FSH). RESEARCH DESIGN AND METHODS: A prospective, randomized, parallel-group, multicentre study was carried out in tertiary care and academic medical centres. Women with anovulatory amenorrhoea > or = 1 year, serum oestradiol (E(2)) < 60 pg/mL (< 220 pmol/L) and low normal serum gonadotrophins were randomized in cycle A to a fixed daily dose of recombinant human (r-h) FSH (150 IU) and r-hLH 0, 25, 75 or 225 IU. Cycles B and C were not randomized. MAIN OUTCOME MEASURES: Follicular development, ovulation and luteinization. RESULTS: In cycle A, follicular development was achieved by 63.6% (7/11), 100% (9/9), 72.7% (8/11) and 66.7% (6/9) of patients who received r-hFSH and r-hLH 0, 25, 75 or 225 IU/day, respectively (p = not significant). Among patients with basal serum LH of < 1.2 IU/L, a dose-response relationship of r-hLH to follicular development was observed (p = 0.039). Fourteen of 34 patients (41.2%) wishing to conceive became pregnant. Among patients with hypogonadotrophic hypogonadism (HH) treated with r-hFSH alone, a transition from LH dependence to independence was observed between basal LH values of > or = 1.2 IU/L and < or = 1.6 IU/L. The r-hLH was well tolerated and no serious adverse events occurred during treatment. The most common treatment-related events were related to the reproductive system and the gastrointestinal tract. CONCLUSIONS: Recombinant human LH provides a safe treatment option for women with HH. This small study also provided evidence suggestive of an LH threshold: follicular development was suboptimal when less than 75 IU/day r-hLH was administered.


Subject(s)
Amenorrhea/drug therapy , Anovulation/drug therapy , Follicle Stimulating Hormone, Human/deficiency , Follicle Stimulating Hormone, Human/therapeutic use , Hormone Replacement Therapy , Luteinizing Hormone/deficiency , Luteinizing Hormone/therapeutic use , Ovarian Follicle , Adolescent , Adult , Amenorrhea/blood , Anovulation/blood , Estradiol/blood , Female , Follicle Stimulating Hormone, Human/adverse effects , Humans , Luteinizing Hormone/adverse effects , Pregnancy , Recombinant Proteins/adverse effects , Recombinant Proteins/therapeutic use
4.
Clin Endocrinol (Oxf) ; 67(4): 563-9, 2007 Oct.
Article in English | MEDLINE | ID: mdl-17692110

ABSTRACT

OBJECTIVE: To provide evidence of efficacy and safety for use of lutropin alfa in inducing follicular development and pregnancy in hypogonadotrophic hypogonadal women with profound gonadotrophin deficiency. DESIGN: An open-label, noncomparative extension of a randomized, double-blind, placebo-controlled study PATIENTS: A total of 31 hypogonadotrophic hypogonadal women with profound gonadotrophin deficiency in 23 medical centres in four countries were studied. INTERVENTIONS: Lutropin alfa 75 IU and follitropin alfa (75-225 IU), individually based on each patient's response as is consistent with usual medical practice. MEASUREMENTS: Follicular development as defined by (i) at least one follicle >or= 17 mm; (ii) preovulatory serum oestradiol level >or= 109 pg/ml on the day of hCG administration; and (iii) midluteal phase P(4) level >or= 7.9 ng/ml. Pregnancy and over-response leading to cycle cancellation were considered treatment successes. Pregnancy rates were assessed. RESULTS: In a total of 54 cycles, 27 of 31 (87.1%) profoundly gonadotrophin-deficient patients achieved follicular development within three cycles. Twenty of 27 patients (74.1%) who achieved follicular development and received hCG became pregnant; 16 (59.3%) continued to clinical pregnancy. One patient was hospitalized for severe ovarian hyperstimulation syndrome. Lutropin alfa was well tolerated. CONCLUSIONS: Coadministration of lutropin alfa 75 IU and follitropin alfa is safe and effective in inducing follicular development and pregnancy in hypogonadotrophic hypogonadal women with profound gonadotrophin deficiency in a setting consistent with established medical practice.


Subject(s)
Fertility Agents, Female/therapeutic use , Glycoprotein Hormones, alpha Subunit/therapeutic use , Gonadotropins/deficiency , Hypogonadism/therapy , Infertility, Female/drug therapy , Luteinizing Hormone/therapeutic use , Adult , Estradiol/blood , Female , Follicle Stimulating Hormone/therapeutic use , Humans , Ovulation Induction/methods , Pregnancy , Pregnancy Outcome , Safety
5.
Fertil Steril ; 82(6): 1587-93, 2004 Dec.
Article in English | MEDLINE | ID: mdl-15589864

ABSTRACT

OBJECTIVE: To evaluate the pharmacokinetic, pharmacodynamic, and safety profiles of the aromatase inhibitor anastrozole in healthy, premenopausal women. DESIGN: Phase I, single-center study. SETTING: Infertility clinic. PATIENT(S): Twenty-six women with regular ovulatory cycles: 20 received either a single dose of 5 mg, 10 mg, 15 mg, or 20 mg anastrozole, or remained untreated; 6 received five daily doses of 10 mg or 15 mg anastrozole. INTERVENTION(S): Anastrozole was administered on cycle day 2 for the single-dose groups and on days 2-6 for the multiple-dose groups. Ultrasound follicular development and endometrial biopsies were performed. Safety was determined from adverse event reports and laboratory parameters. MAIN OUTCOME MEASURE(S): Pharmacokinetics, pharmacodynamics, and safety. RESULT(S): The pharmacokinetics of anastrozole were linear, predictable, and consistent with previously published data in healthy volunteers. In the single-dose groups, E2 levels reached their nadir 3-6 hours after administration, decreasing by an average of 39% from baseline. Follicle-stimulating hormone levels rose by 13%, 52%, 49%, and 75% in the 5-mg, 10-mg, 15-mg, and 20-mg groups, respectively, at approximately 24 hours after dosing. Most subjects recruited just one mature follicle, with no apparent effect on endometrial maturation. No safety concerns were noted. CONCLUSION(S): Anastrozole was well tolerated and suppressed E2 levels, with a resultant increase in FSH.


Subject(s)
Aromatase Inhibitors/pharmacology , Aromatase Inhibitors/pharmacokinetics , Estrogen Antagonists/pharmacology , Estrogen Antagonists/pharmacokinetics , Nitriles/pharmacology , Nitriles/pharmacokinetics , Premenopause , Triazoles/pharmacology , Triazoles/pharmacokinetics , Adult , Anastrozole , Aromatase Inhibitors/administration & dosage , Aromatase Inhibitors/adverse effects , Dose-Response Relationship, Drug , Drug Administration Schedule , Endometrium/drug effects , Endometrium/physiology , Estradiol/blood , Estrogen Antagonists/adverse effects , Female , Follicle Stimulating Hormone/blood , Gastrointestinal Diseases/chemically induced , Headache/chemically induced , Humans , Menstruation Disturbances/chemically induced , Nitriles/administration & dosage , Nitriles/adverse effects , Ovarian Follicle/diagnostic imaging , Ovarian Follicle/drug effects , Ovarian Follicle/physiology , Reference Values , Time Factors , Triazoles/administration & dosage , Triazoles/adverse effects , Ultrasonography
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