Effectiveness of a low gonadotrophin-releasing hormone antagonist dose in preventing premature luteinizing hormone rise during controlled ovarian stimulation

The current prospective randomized study was designed to test the efficacy of a low dose (0.125 mg/day) of the gonadotrophin-releasing hormone antagonist cetrorelix in preventing premature luteinizing hormone (LH) rise during controlled ovarian stimulation in comparison with the standard dose of 0.25 mg/day. Ovarian stimulation was started with 225 IU of recombinant follicle stimulating hormone (FSH) on day 2 of the menstrual cycle. Cetrorelix was injected daily from day 6 of gonadotropin administration. Blood was sampled from each woman on day 3 of ovarian stimulation and then daily from day 5 onward up to human chorionic gonadotropin administration for analysis of FSH, LH, progesterone, and estradiol. LH rise was defined as serum LH?≥10 mIU/ml. There were 40 patients receiving cetrorelix at 0.25 mg/day and 36 patients receiving cetrorelix at 0.125 mg/day. Premature LH rise was recorded in 10% of patients injecting antagonist at 0.25 mg/day and in 14% of patients administered with antagonist at 0.125 mg/day. These frequencies did not differ statistically. In conclusion, our results suggest that a cetrorelix dose of 0.125 mg/day is effective as the standard dose (0.25 mg/day) in preventing premature LH rise during controlled ovarian stimulation.     

Comparative efficacy and safety of cetrorelix with or without mid-cycle recombinant LH and leuprolide acetate for inhibition of premature LH surges in assisted reproduction

An open label, randomized, multi-centre study was performed to compare cetrorelix and leuprolide acetate for prevention of premature LH surge and to assess whether patients treated with cetrorelix benefit from addition of recombinant human (r-h)LH. Normo-ovulatory women (n = 74) undergoing ovarian stimulation prior to intracytoplasmic sperm injection were treated with leuprolide acetate (n = 25) before ovarian stimulation with recombinant human FSH (r-hFSH) or with cetrorelix 3 mg on stimulation day 7 (with (n = 25) or without (n = 24) r-hLH 150 IU on days 7-10). The main outcome measures were the number of metaphase II (MII) oocytes retrieved; secondary efficacy end-points; adverse events (AE) and other safety measures. There were no significant differences between groups for MII oocytes retrieved, duration of stimulation, total r-hFSH dose and pregnancy rates. The group treated with cetrorelix alone had a significantly lower concentration of oestradiol per follicle compared with the other groups. The majority of AE were mild to moderate in severity. Cetrorelix and leuprolide acetate appear to have comparable efficacy and safety, although cetrorelix has the advantage of typically requiring only one injection.     

Antigonadotropic effects of a 19-nor-progesterone derivative: the example of nomegestrol acetate

The antigonadotropic activity of progestins, progesterone and 19-norprogesterone derivatives, is generally used in clinical practice to treat hyperestrogenic symptoms and to provide a contraceptive effect in women with intolerance to exogenous estrogens.Our purpose was to review data from clinical pharmacological trials and from efficacy and/or safety clinical studies on progestin antigonadotropic properties with the example of nomegestrol acetate administered at the dose of 5 mg daily during 20 or 21 days per cycle.The antigonadotropic effect was shown by the effect on gonadotropins: in normally cycling premenopausal women, gonadotropin ovulatory peak was constantly inhibited, LH secretion was decreased and FSH increase at the end of the control cycle was inhibited by nomegestrol acetate (n = 5). Moreover, LH basal levels, LH response to exogenous GnRH and aeras under the curves (AUC) of LH pulsatile profile were decreased in the treated cycle (n = 11) compared to the control cycle. For both LH and FSH, the basal levels, the response to GnRH and the AUC of pulsatile profile were decreased by nomegestrol acetate compared to placebo in postmenopausal women; moreover, the frequency but not the amplitude of LH pulses was decreased. Depending on the woman's ovarian functional status, the effects of nomegestrol acetate on FSH were divergent (FSH increased before menopause and decreased at postmenopause), perhaps due to experimental conditions or a direct effect on the ovary. In postmenopausal women, the action of nomegestrol acetate on gonadotropin secretion was not modified by flutamide, a pure antiandrogen; this suggests that the antigonagotropic activity of the progestin is not mediated through the androgen receptor and it acts probably through the progesterone receptor.This antigonadotropic effect had an impact on ovarian function: in premenopausal women on nomegestrol acetate (n = 21), progesterone secretion was inhibited attesting to the absence of corpus luteum, the pre-ovulatory peak of estradiol was inhibited and plasma estradiol concentrations were decreased. The antigonadotropic activity of nomegestrol acetate results in reinforcement of its antiestrogenic activity, particurlarly on the endometrium and enables to treat the frequent clinical hyperestrogenic symptoms of the perimenopause without negative metabolic or hemostatic effects.In the efficacy and/or safety studies, no pregnancy was observed with nomegestrol acetate administered in antigonadotropic sequence, during 1355 treated cycles and the hormonal data (n = 205) were in agreement with the antigonadotropic effects of the progestin demonstrated in the clinical pharmacological studies.Furthermore, at the same dose and sequence, nomegestrol acetate, in addition to its inhibitory effect on ovulation, induces changes in the endometrium rendering it unable to implantation and in the cervical mucus to rendering it hostile to spermatozoa migration. However, it must be emphasized that data from experimental conditions required for the calculation of the Pearl Index are not available and therefore there is no legal claim for "contraception".     

Is a lower dose of cetrorelix acetate effective for prevention of LH surge during controlled ovarian hyperstimulation?

Purpose: This study was performed to evaluate whether a lower dose (0.2 mg) of cetrorelix would prevent premature LH surge in patients undergoing controlled ovarian hyperstimulation. Methods: Controlled ovarian hyperstimulation was carried out in 45 patients, starting on menstrual cycle day 3 with recombinant FSH (r-FSH), and a cetrorelix of 0.2 mg was administered from day 5 evening of ovarian stimulation until the day before hCG injection. Results: There was a statistically significant decrease in serum LH level one day after the first cetrorelix injection and on the day of hCG administration. Serum LH concentrations were maintained constantly low during the follicular phase with no premature LH surge occurring in any of the patients. Clinical pregnancy was achieved for 18 women (40%), with one of these experiencing intrauterine fetal death before 12 week' gestation. Conclusion: This study demonstrates that a daily dose of cetrorelix 0.2 mg is able to prevent premature LH surge.     

Programming ovulation in the menstrual cycle by a simple innovative approach: back to the future of assisted reproduction.

OBJECTIVE: To synchronize the intercycle FSH elevation with exogenous E2 for programming ovulation in the menstrual cycle. DESIGN: Open single-arm study. SETTING: Teaching hospital. PATIENT(S): Twenty-six patients with infertility whose menstrual cycles normally lasted 25-35 days and who underwent our routine programming method for postcoital tests and ovulation evaluations. INTERVENTION(S): Participants received estradiol valerate (2 mg) twice a day from day 25 of the previous cycle until 1-15 days after the onset of menses. Women had ultrasonography on the last day of E2 treatment or on functional day 0 and 13 days later or on functional day 13. Hormones were determined on functional days 0, 3, 9, and 13. The increase in FSH in response to E2 withdrawal was defined as deltaFSH. MAIN OUTCOME MEASURE(S): LH surge and other ovulatory indices on functional day 13. RESULT(S): On functional day 13, 73% of the women had an LH surge. Fifteen percent had evidence of previous ovulation with low LH and elevated plasma P levels, and the remaining 12% had low LH levels and no evidence of past or imminent ovulation. Women with evidence of early ovulation were older and had higher FSH signal amplitude. CONCLUSION(S): It is feasible and practical to program ovulation in the menstrual cycle with exogenous E2. In 73% of women, the true duration of the follicular phase (intercycle FSH elevation to LH surge interval) remained constant (13 days). Hence, common fluctuations in menstrual cycle length mainly result from variations in the timing of the intercycle FSH elevation. Although rare, truly short follicular phases also exist (15%). This simple and practical system for programming natural ovulation offers new possibilities for using the menstrual cycle in assisted reproductive technology, at least in selected individuals.     

Effect of a lower-dose cetrorelix acetate protocol on in-vitro fertilization outcome

OBJECTIVE: To determine whether a low initial dosage of cetrorelix acetate could prevent a premature luteinizing hormone (LH) surge in women undergoing controlled ovarian stimulation. METHOD: Treatment with a recombinant follicle stimulating hormone was started on Day 3 of the menstrual cycle, and 0.125 mg of cetrorelix was injected daily from Day 5 of the ovarian stimulation until the diameter of the dominant follicle reached at least 16 mm. The dosage was then doubled and maintained at 0.250 mg/day until the day before the injection of human chorionic gonadotropin. RESULT: There was a significant decrease in serum LH concentration 1 day after doubling the cetrorelix dosage, and the LH concentration remained low during the follicular phase. Clinical pregnancy occurred in 18 women (42.8%), with 2 intrauterine fetal deaths before the 12th week. CONCLUSION: Increasing the cetrorelix dosage from 0.125 to 0.250 mg/day when the follicular size is appropriate can prevent a premature LH surge.     

Effect of premenopausal castration and incremental dosages of conjugated equine estrogens on plasma follicle-stimulating hormone, luteinizing hormone, and estradiol.

Plasma levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), and estradiol (E2) were measured serially in 11 premenopausal patients before and after hysterectomy with bilateral salpingo-oophorectomy. One week after operation an incremental dosage regimen of conjugated estrogens (CEE) in tablet form was commenced on a basis of two weeks with therapy (0.3, 0.625, 1.25, and finally 2.5 mg.), with each dose interspersed by two weeks without therapy. FSH, LH and E2 levels were measured at the end of each period with and without therapy. E2 levels fell within 24 hours of operation while FSH and LH levels rose gradually. CEE therapy produced an elevation of E2, but circulating concentrations comparable to the premenopausal values were only maintained during the dosage periods of 0.625 and 1.25 mg. of CEE. In only one instance did CEE succeed in reducing FSH to premenopausal levels, and that was at a dosage of 2.5 mg., in which instance the E2 level was higher than the premenopausal value. LH was never reduced to a premenopausal level. Thus, the data indicate that CEE alone in dosages up to 2.5 mg. per day was unable to reproduce in postmenopausal women the gonadotropin and E2 blood serum levels shown to exist prior to oophorectomy. Usual CEE treatment after menopause, therefore, in itself does not represent physiologic "hormone replacement therapy," if defined as the dosage required to maintain premenopausal circulating concentrations of reproductive hormones.     

Suppressive action of norethisterone enanthate and acetate on gonadotropin. (FSH and LH) levels. Radioimmunoassay in eugonadal and postmenopausal women

The suppressive action of norethisterone enanthate and acetate on follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels was studied by radioimmunoassay in postmenopausal and normally menstruating women. Postmenopausal women, injected with 200 mg of norethisterone acetate, intramuscularly, showed a marked, rapid, and prolonged decrease in serum LH levels. FSH also declined but the decrease was less rapid, less pronounced, and briefer. 1 month after injection, FSH values had returned to pretreatment levels. Oral norethisterone acetate, administered in .3 mg/day doses for 16 days to postmenopausal subjects, did not produce a statistically significant change in serum FSH levels, although serum LH concentrations gradually declined until the end of the treatment period. An oral dose of .3 mg./day of norethisterone acetate suppressed FSH and LH peaks in normally menstruating women who had displayed the peaks prior to treatment. Baseline levels of FSH and LH, however, were not lowered.     

Concentration-dependent mechanisms of ovulation inhibition by the progestin ST-1435

We summarize the hormonal profiles of women at different stages of inhibition of ovarian function during sustained-release subcutaneous treatment with a progestin, ST-1435. In the highest release group of ST-1435, a decrease in the luteinizing hormone (LH)follicle-stimulating hormone (FSH) ratio was found; and in spite of follicular phase levels of plasma FSH, inhibition of folliculogenesis, as judged by plasma estradiol (E2) concentrations below 60 pg/ml, occurred during the entire treatment period of 230 days. This may be indicative of a direct action of ST-1435 on the ovaries. When the average plasma concentration of ST-1435 decreased below 100 pg/ml, follicle development had started in most of the study subjects. At that time, the LH/FSH ratio had normalized to that found during the follicular phase of the normal menstrual cycle. In spite of the E2 rise during follicular development, no midcycle gonadotropin surges or subsequent elevations in plasma progesterone concentrations were found, thus indicating that the positive feedback action of E2 on gonadotropins was blocked by this progestin. We infer that the mechanism of inhibition of ovulation by sustained parenteral treatment with the progestin ST-1435 is concentration dependent, in such a manner that lower plasma concentrations of ST-1435 act on the hypothalamus and/or pituitary, whereas at higher plasma concentrations of ST-1435, a direct effect on the ovaries is also achieved.     

Treatment of uterine leiomyomata with a luteinizing hormone-releasing hormone agonist: the possibility of nonsurgical management in selected perimenopausal women

OBJECTIVE: To evaluate the efficacy of luteinizing hormone-releasing hormone agonist (LH-RH-a) in the treatment of leiomyomata. DESIGN: A retrospective randomized trial. SETTING: Hospital department of obstetrics and gynecology. PATIENTS: Twenty-five women, ages 36 to 54 years with symptomatic uterine leiomyomata, were divided into two groups according to the responsiveness to LH-RH-a: group A patients reached menopause after LH-RH-a, whereas resumption of menstruation occurred within 12 weeks after cessation of therapy in group B. INTERVENTIONS: Luteinizing hormone-releasing hormone agonist was administered intranasally three times a day with 150 micrograms insufflation of one spray in each nostril (total dose: 900 micrograms/d). MAIN OUTCOME MEASURES: Efficacies of treatment were assessed in terms of uterine volume, hemoglobin concentrations, serum levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol (E2), and bone density during and after treatment. RESULTS: In both groups, hemoglobin concentrations increased significantly after 16 weeks of treatment. A significant reduction in uterine volume was observed in both groups. After completing therapy, there was no further significant change in uterine volume in group A, whereas uterine volume in group B returned to pretreatment values. Serum LH and FSH concentrations were suppressed during treatment, but those gonadotropins in group A increased significantly up to the menopausal levels after treatment. Serum E2 concentrations in both groups showed consistent suppression by the end of the first treatment cycle. After cessation of therapy, serum E2 levels on group A remained in the castrate range, whereas E2 in group B returned to pretreatment levels, concomitant with the return of normal ovulation. CONCLUSIONS: Intranasal administration of LH-RH-a was successful in significantly decreasing uterine volume and increasing hemoglobin concentration in premenopausal women with leiomyomata.     

Metformin therapy improves ovulatory rates, cervical scores, and pregnancy rates in clomiphene citrate-resistant women with polycystic ovary syndrome.

OBJECTIVE: To evaluate the effect of metformin therapy on hyperandrogenism, insulin resistance, cervical scores, ovulation, and pregnancy rates in clomiphene citrate-resistant women with polycystic ovary syndrome (PCOS). DESIGN: Prospective, randomized, double-blind, placebo-controlled study. SETTING: Infertility clinic of a tertiary referral center. PATIENT(S): Fifty-six women with clomiphene citrate-resistant PCOS. INTERVENTION(S): Two cycles of oral metformin therapy (850 mg, twice daily) in group I and placebo therapy (twice daily) in group II. Clomiphene citrate (100 mg/day) on cycle days 3-7 of the second cycle in both groups. MAIN OUTCOME MEASURE(S): Insulin, T, DHEAS, FSH, LH, body mass index (BMI), waist-to-hip ratio, endometrial thickness, cervical score, ovulation, and pregnancy rates in clomiphene-induced cycles after metformin therapy. Result(s): Metformin therapy resulted in a significant decrease in total T, LH level, LH/FSH ratio, insulin resistance, and mean BMI. No difference in waist-to-hip ratio, DHEAS level, and fasting insulin level was observed. Clomiphene citrate induction resulted in higher ovulation rates and thicker endometrium in the metformin group than in the placebo group. There was higher cumulative pregnancy rate in the metformin group; however, there was no significant difference in the pregnancy rate between the two groups. CONCLUSION(S): Metformin therapy not only decreases hyperandrogenism and insulin resistance but also improves ovulation rates, cervical scores, and pregnancy rates in clomiphene citrate-resistant women with PCOS.     

Effects of danazol on pulsatile gonadotropin patterns and on serum estradiol levels in normally cycling women

The effect of danazol on pulsatile luteinizing hormone (LH), follicle-stimulating hormone (FSH), and estradiol (E2) secretion was examined in eight premenopausal women by serial blood sampling on day 10 of the control and first treatment cycles and during 2 subsequent months of treatment. The mean frequency of LH pulses decreased, while the mean pulse amplitude and increment increased (P less than 0.05). The mean LH concentrations were significantly suppressed in four of eight subjects. The mean frequency of E2 pulses, mean increment, and mean integrated area were decreased (P less than 0.05). The mean integrated FSH area did not change significantly during treatment, and we were not able to demonstrate unequivocal FSH pulses. We conclude that danazol in premenopausal women (1) lowers serum E2 concentrations by decreasing the frequency and increment of E2 pulses, (2) prevents compensatory gonadotropin rise, and (3) lowers the frequency but increases the amplitude and increment of LH pulses. The latter change reflects probably divergent effects of the drug on the pituitary and hypothalamus and results in an inconsistent lowering of basal LH levels.     

The effect of a GnRH antagonist on follicle maturation in normal women

Research questionGanirelix is a gonadotrophin-releasing hormone (GnRH) antagonist used for the prevention of premature LH surge during ovarian stimulation. What is the impact of ganirelix on follicle maturation in normal women?DesignTen normally cycling women were investigated during two menstrual cycles, i.e. cycle 1 (control) and cycle 2 (ganirelix). During both cycles, daily blood samples were taken from day 2, while transvaginal ultrasound scans were performed on cycle days 8 and 10 and daily thereafter. During cycle 2, all women were given 0.25 mg/day subcutaneous injections of the GnRH antagonist ganirelix from day 2 until the day of the endogenous LH surge onset in cycle 1.ResultsDuring treatment with ganirelix, serum FSH and oestradiol concentrations remained stable, while those of LH decreased significantly on days 3, 4, 7 and 9 (P < 0.05) compared with controls. Nevertheless, there was no significant within-cycle variation in LH concentrations. From day 10 onwards, no follicle maturation was observed in cycle 2, in contrast to cycle 1. Ovulation occurred in 9 of 10 women in cycle 1. In cycle 2, ovulation was delayed by at least 1 week in eight women. Follicle growth and ovulation occurred in only one woman while on ganirelix treatment.ConclusionsThis study demonstrates for the first time that in normal women dominant follicle selection failed during treatment with ganirelix. As there was a similar gonadotrophin profile in the two cycles, it is suggested that ganirelix interferes with the process of follicle selection by acting in the ovary.     

Effect of nomegestrol acetate, a new 19-nor-progesterone derivative, on pituitary-ovarian function in women

Summary. After two control cycles, 13 normally menstruating women were treated from day 5 to 25 of the third consecutive cycle with nomegestrol acetate (NOM Ac) 1.25, 2.5 or 5 mg once a day. Plasma oestradiol, FSH and LH concentrations were assayed daily from day 5 to day 25 and plasma progesterone concentrations from day 12 to day 25. Ovulation was inhibited in every woman; LH and progesterone levels were uniformly depressed. With 5 and 2.5 mg/day, plasma oestradiol remained low with high FSH values. With 1.25 mg/day, oestradiol concentrations reached levels similar to those achieved during the control follicular phase, with a concomitant decrease in FSH secretion. These results show an hypothalamic-pituitary effect and suggest an ovarian action, both responsible for a potentially useful contraceptive property.     

Effect of oral estriol on abnormal plasma FSH and LH concentrations in women with unexplained infertility; conception in a patient with elevated FSH and LH

Estriol tablets in the daily dose of 0.25, 0.5 or 1.0 mg were administered for ten days prior to the expected ovulation in six women with unexplained, long-standing infertility, regular, apparently ovulatory cycles, and normal cyclic changes in estradiol and progesterone. Five of six had abnormal FSH and LH patterns contrasting with normal estradiol and progesterone secretion during the control cycle. There was an increase in the midcycle LH surge at two lower doses of estriol and at the highest dose there was a 7-9 day delay observed in the estradiol peak, LH surge and menstrual period in the patient with the normal control cycle. This contradicts previously published data that estriol does not suppress or delay ovulation at the dose as high as 6 mg/day. In four patients with persistently elevated LH and low FSH concentrations, there was little change in the pattern of FSH, LH, estradiol or progesterone secretion during treatment. In the last patient, who had during the control cycle plasma FSH and LH concentrations fluctuating between high normal and menopausal range, indicating "premature ovarian failure" and absence of ovarian follicles, essentially normal cyclic pattern of both gonadotropins with exception of few individual values appeared during treatment. The patient conceived during the last cycle of treatment (estriol 1.0 mg/day). Our study demonstrates that high concentrations of FSH and LH may not necessarily indicate the absence of oocytes and documents previously reported, but never documented occurrence of a conception during estrogen therapy in such a case.     

Urinary follicle-stimulating hormone peak as a biomarker for estimating the day of ovulation

OBJECTIVE: To evaluate urinary follicle-stimulating hormone (FSH) as a biomarker for the day of ovulation. DESIGN: Prospective observational study. SETTING: Clinical research center. PATIENT(S): Thirteen women were monitored with measurements of serum and urinary hormones and ovarian ultrasonography during 20 menstrual cycles. Data on urinary hormones and ultrasound evaluations from a total of 65 menstrual cycles from 42 women were analyzed. INTERVENTION(S): Blood and/or urine samples were collected daily. Daily transvaginal ultrasonography was used to detect follicular collapse. MAIN OUTCOME MEASURE(S): LH, FSH, and E(2) were measured in serum. FSH, estrone conjugates (E1C), and pregnanediol-3-glucuronide (PdG) were analyzed in urine. The day of luteal transition (DLT) was calculated using two algorithms. RESULT(S): In 20 cycles, the urinary FSH peak was closer to the day of follicular collapse (-0.85 days) than was the peak day of serum E(2) and the day of luteal transition, as calculated by one algorithm. The FSH peak was not closer to the day of follicular collapse than the peak values of urinary LH, serum FSH, or the day of luteal transition as calculated by a second algorithm. The most consistent correspondence between a hormone peak and ovulation was for serum E(2), serum FSH, serum LH, and urinary FSH. In 65 cycles for which urinary hormone data and ultrasound evaluations were available, the urinary FSH peak occurred within 1 day of follicular collapse in 97% of cycles. CONCLUSION(S): Urinary FSH is a useful biomarker for estimating the day of ovulation in population-based studies.     

Effect of nomegestrol acetate, a new 19-nor-progesterone derivative, on pituitary-ovarian function in women

After two control cycles, 13 normally menstruating women were treated from day 5 to 25 of the third consecutive cycle with nomegestrol acetate (NOM Ac) 1.25, 2.5 or 5 mg once a day. Plasma oestradiol, FSH and LH concentrations were assayed daily from day 5 to day 25 and plasma progesterone concentrations from day 12 to day 25. Ovulation was inhibited in every woman; LH and progesterone levels were uniformly depressed. With 5 and 2.5 mg/day, plasma oestradiol remained low with high FSH values. With 1.25 mg/day, oestradiol concentrations reached levels similar to those achieved during the control follicular phase, with a concomitant decrease in FSH secretion. These results show an hypothalamic-pituitary effect and suggest an ovarian action, both responsible for a potentially useful contraceptive property.     

A randomized comparison of ovulation induction and hormone profile between the aromatase inhibitor anastrozole and clomiphene citrate in women with infertility.

BACKGROUND: IN the present study we evaluated and compared the effects of ovulation and hormonal dynamics induced by anastrozole and clomiphene citrate in women with infertility. MATERIALS AND METHODS: Thirty-three infertile patients, aged 25-41 years, were enrolled. Patients received either anastrozole 1 mg daily (AI group) or clomiphene citrate 100 mg daily (CC group) from cycle day 3 to day 7. Number of mature follicles (> or =18 mm), endometrial thickness, pregnancy rate and serial hormone profiles (follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E(2)), testosterone and progesterone) were measured on cycle day 3, day 8, day 10, the day of intrauterine insemination (IUI), day 7 after IUI and day 14 after IUI. RESULTS: Baseline parameters were similar in the two groups, including age, body mass index, infertility duration and day-3 serum hormones except FSH. The mean FSH value on day 3 was significantly different (4.3 mIU/ml in the AI group vs. 6.3 mIU/ml in the CC group; p < 0.05). The women receiving anastrozole had fewer ovulatory follicles (1.2 in the AI group vs. 1.8 in the CC group; p < 0.05) and a thicker endometrium (10.6 mm in the AI group vs. 7.8 mm in the CC group; p < 0.05). The levels of progesterone and testosterone were similar during ovulation stimulation cycles in both groups. On the other hand, the AI group had a significantly higher LH level but a significantly lower E(2) level in the stimulation cycle. CONCLUSION: Anastrozole has a high pregnancy rate, although it induces fewer ovulatory follicles compared with clomiphene citrate. The two drugs gave different responses of FSH, LH and E2 during stimulation cycles.     

Serum hormone level and Kupperman menopausal complaints in sexually mature women with disturbance of ovulation

In 103 sexually mature women with disturbance of ovulation, a possible relationship between Kupperman menopausal complaints and endocrinological status was investigated to find the cause of climacteric syndrome. The Kupperman index was increased as the disturbance of ovulation was advanced from the stage of anovulatory cycle to amenorrhea I and further to amenorrhea II. In parallel with the advance in disturbance of ovulation, serum FSH and LH levels rose significantly, and serum estrone (E1) and estradiol (E2) levels dropped. Prolactin (PRL) showed a tendency to decrease. There were some hormonal patterns characteristic of individual complaints; hot flush was associated with increased FSH and LH, and decreased E1 and E2; difficulty in falling asleep, excitability, and fatigability, with increased FSH and LH, and decreased E2; nervousness, with increased LH and decreased E2; headache, with increased LH and PRL, and decreased E2; feeling of cold, with decreased E2 and PRL; and numbness and shoulder stiffness, with decreased E2. In sexually mature women, the complaints associated with abnormal levels of two or more kinds of hormones seemed to be most specifically related with decreased E2, followed by increased LH. Fatigability and headache developed specifically in the ovulatory phase of women with normal menstrual cycles (105 subjects), suggesting that these two complaints are closely related to increased LH. These results indicate that the majority of Kupperman menopausal complaints have their individually specific endocrinological cause, and that they may develop even in sexually mature women if those specific conditions exist. In climacteric syndrome in a narrow sense (i.e., dysautonomic type), each complaint may also have its specific endocrinological cause.