Biomedical subjects

J Schoemaker

Publications and source records attributed to J Schoemaker.

At least 37 records · Page 2Linked to original sources

PubMed1999

GH substitution does not alter the pulsatile pattern of LH in amenorrhoeic growth hormone deficient women.

OBJECTIVE: GH substitution in GH-deficient (GHD) children promotes pubertal development. In some GHD women, secondary amenorrhoea occurs after discontinuation of GH treatment. This study was designed to investigate whether GH substitution directly influences the GnRH pulse generator. For this reason, the pulsatile release of LH was studied in amenorrhoeic GHD women before and during GH substitution. DESIGN: GH deficiency was confirmed by an insulin tolerance test. During a 24-h period, blood samples were drawn every 10 min for determination of LH, FSH and GH levels. Oestradiol and IGF-1 were determined at 1000 h and 2200 h. After the first test day, patients started with GH substitution, 0.25 IU/kg/week. During month 6 of GH treatment, the 24 h blood sampling was repeated. SUBJECTS: Ten amenorrhoeic GH-deficient women participated in the trial. All were diagnosed as GH deficient during childhood or adolescence. Eight of them had been treated with GH during childhood. Seven women suffered from primary amenorrhoea and three from secondary amenorrhoea. Six women were started with GH substitution after the first test day (according to randomization in a larger study). MEASUREMENTS: LH and GH were determined every 10 min and FSH every 60 min. LH pulse detection was conducted using a validated statistical method. RESULTS: Prior to GH treatment, the LH pulse interval did not show a diurnal pattern as found during normal pubertal development. During GH treatment, IGF-1 levels rose significantly. No differences were found in mean LH, LH pulse amplitude and LH pulse interval before and during GH treatment. Oestradiol levels did not change either. CONCLUSIONS: GH substitution in amenorrhoeic GH-deficient women does not alter the pulsatile pattern of LH. This may suggest that GH treatment does not influence central nervous system control of gonadotropin secretion in GHD patients.

Adult↗

PubMed1999

Successful in-vitro fertilization in a natural cycle after four previously failed attempts in stimulated cycles: case report.

A case is reported of successful in-vitro fertilization (IVF) and pregnancy in a natural cycle after four previously failed attempts with stimulated cycles. The patient began treatment at the age of 36 years and underwent four stimulated IVF cycles, each time with three embryos of good quality transferred. In one attempt, three cryopreserved embryos were transferred in a natural cycle. The patient failed to conceive. At the age of 38 years, the patient was entered into a natural cycle IVF programme. The patient conceived twice in each of her first two attempts but unfortunately aborted. In her third natural cycle of IVF, again with one oocyte obtained and one embryo transferred, the patient conceived and had a full term gestation. It is concluded that IVF in a natural cycle is a viable option for infertile women with blocked Fallopian tubes who have normal ovulatory menstrual cycles.

Adult↗

PubMed1999

Fluctuations in CA 125 and CA 15-3 serum concentrations during spontaneous ovulatory cycles.

The aim of this study was to investigate cycle dependent changes of serum CA 125 and CA 15-3 concentrations during spontaneous ovulatory cycles. Twenty apparently healthy women with spontaneous menstrual cycles attending our infertility clinic were included. Of these women, 18 had occluded tubes as a result of sterilization. Ovulation was confirmed by luteinizing hormone test and ultrasonography and, to exclude endometriosis, a laparoscopy was performed. Serum samples for CA 125, CA 15-3, 17 beta-oestradiol and progesterone determinations were taken every second day starting on the 2nd day of the cycle until the 7th day of the next cycle. After correction for inter-individual variation in serum concentrations, highest CA 125 concentrations were found during the menstruation. During the follicular and peri-ovulatory phase CA 125 serum concentrations were lowest. For CA 15-3, serum concentrations were not statistically different throughout the cycle. CA 125 and oestradiol concentrations were negatively correlated, CA 15-3 and oestradiol concentrations were positively correlated. Absolute serum concentrations of both CA 125 and CA 15-3 vary among females. Within the female, fluctuations of CA 125 are phase related. In the population studied most of the patients had tubal obstruction and high CA 125 serum concentrations during menstruation, which revokes the theory that the menstrual rise of CA 125 is due only to retrograde menstruation.

Adult↗

PubMed1999

Variation of luteinizing hormone and androgens in oligomenorrhoea and its implications for the study of polycystic ovary syndrome.

We measured luteinizing hormone (LH) and androgen concentrations in patients at different phases of the oligomenorrhoeic cycle and compared the results with those of patients with normogonadotrophic amenorrhoea. Several blood samples separated by >/=7 days were obtained from each of 72 patients with oligomenorrhoea and 18 with normogonadotrophic amenorrhoea. The oligomenorrhoeic cycle was divided into five phases: the postmenstrual phase week 1 (day 1-7) and week 2 (day 8-14), the specific oligomenorrhoeic phase (SOP, day 15 after a menstruation to day 21 before the next menstruation), the possibly peri-ovulatory phase (days 21-11 before menstruation) and the premenstrual phase (days 10-1 before menstruation). Samples obtained in the possibly peri-ovulatory phase were excluded. Within individuals LH concentrations were significantly higher during the SOP than during all other phases of the oligomenorrhoeic cycle (paired t-test, P = 0.0001-0.03). In contrast to the other phases of the oligomenorrhoeic cycle, no significant differences in gonadotrophins, androgen or oestradiol concentrations were found between the SOP and normogonadotrophic amenorrhoea. In oligomenorrhoea timing of blood sampling influences the measurement of LH and androgen concentrations, and the accurate interpretation of these measurements requires that the dates of menstruation both before and after the sample is taken should be known. In patients with oligomenorrhoea blood samples should be obtained during the SOP, when the endocrinology is comparable with that of normogonadotrophic amenorrhoea.

Adult↗

PubMed1999

Endocrine features of polycystic ovary syndrome in a random population sample of 14-16 year old adolescents.

Hospital based studies have shown that oligomenorrhoeic adolescents have high luteinizing hormone (LH) and androgen concentrations, endocrine signs of polycystic ovary syndrome (PCOS). The prevalence of these abnormalities in an unselected population of adolescents is not known. We determined LH, follicle stimulating hormone (FSH), androstenedione, testosterone, dehydroepiandrosterone sulphate (DHEAS), oestradiol and prolactin concentrations in unselected population samples of adolescents with oligomenorrhoea, secondary amenorrhoea and regular menstrual cycles. A total of 2248 white, west European adolescents, aged 15.3 +/- 0.6 (mean +/- SD) years, participated. Blood was taken from 107 adolescents with regular menstrual cycles, 52 with oligomenorrhoea and four with secondary amenorrhoea. Oligomenorrhoeic adolescents had higher mean LH, androstenedione, testosterone, DHEAS and oestradiol concentrations compared with girls with regular menstrual cycles; 57% of the oligomenorrhoeic girls had LH or androgen concentrations above the 95th centile of adolescents with regular menstrual cycles. None of the 52 oligomenorrhoeic girls and only one of four girls with secondary amenorrhoea had a hypogonadotrophic endocrine pattern. The present study and available literature support the view that oligomenorrhoea in adolescents is not a stage in the physiological maturation of the hypothalamic pituitary-ovarian axis but an early sign of PCOS associated with subfertility. Physicians should consider endocrine evaluation before reassuring oligomenorrhoeic girls or prescribing oral contraceptives to these girls.

Adolescent↗

PubMed1999

Concurrent pulsatile secretion of luteinizing hormone and follicle-stimulating hormone during different phases of the estrous cycle and anestrus in beagle bitches.

The 6-h secretory profiles of LH and FSH and the possible concordance between the episodic release of LH and FSH were studied in 6 beagle bitches during early, mid-, and late anestrus and during the follicular and luteal phases of the estrous cycle. Plasma samples were obtained at 10-min intervals via jugular venipuncture. In all stages of anestrus and in the luteal phase, FSH and LH secretion was pulsatile. All FSH pulses coincided with LH pulses. However, the mean duration of the FSH pulse (115 min) was significantly longer than that of the LH pulse (72 min). The basal plasma LH concentration was low compared with the maximum peak levels, whereas FSH pulses were characterized by relatively low peaks compared with the basal levels. In contrast to the basal plasma LH levels and the area under the curve (AUC) for LH, the basal plasma FSH levels and the AUC for FSH increased significantly as anestrus progressed. During the follicular phase, the secretory pattern of LH was characterized by frequent increases of short duration. During this phase, the basal plasma FSH concentration was relatively low, whereas the basal plasma LH level was high in comparison with that in the other phases of the estrous cycle. The luteal phase was characterized by an increased frequency of LH pulses, a shorter duration of the LH peaks, and a tendency to a lower amplitude of both LH and FSH peaks compared with values observed during anestrus. It is concluded that in the bitch, FSH and LH pulses are released in concordance and that progression from early to late anestrus is associated with an increase in basal plasma FSH concentration without a concomitant rise in basal plasma LH concentrations. The latter suggests that in the bitch an increase in circulating FSH should be considered to be a critical event required for the initiation of ovarian folliculogenesis and consequently for the termination of anestrus.

Anestrus↗

PubMed1999

Growth hormone (GH) substitution in hypogonadotropic, GH-deficient women decreases the follicle-stimulating hormone threshold for monofollicular growth.

The FSH threshold concept for monofollicular growth (which means that at the time the largest follicle reaches 18 mm there are no other follicles with a diameter of 13-18 mm also present) was used during ovulation induction in hypogonadotropic women, who appeared to be GH deficient. This concept was used to investigate whether 1) GH influences the FSH threshold for monofollicular growth and 2) whether such an influence would depend upon the endogenous GH/insulin-like growth factor I (IGF-I)/IGF-binding protein-3 (IGFBP-3) levels. In six hypogonadotropic women the GH response after an insulin challenge did not exceed 6 microg/L. Patients underwent ovulation induction according to a low dose step-up protocol by hMG during two consecutive cycles. GH substitution was provided only during the second cycle. Except for one GH treated cycle, all cycles were ovulatory. IGF-I levels as well as IGFBP-3 levels significantly increased (P < 0.01) during GH substitution. Monofollicular growth was not achieved in the first cycles. In five of six GH-substituted cycles, monofollicular growth was obtained. FSH threshold levels decreased in all patients during GH substitution. The FSH area under the curve was negatively correlated to IGF-I (r = -0.6; P < 0.05) and IGFBP-3 (r = -0.6; P < 0.05). The results of this study indicate that GH may play a role in the physiological growth of the follicle; most likely this occurs by influencing the IGF-I or IGFBP-3 levels. GH appears to selectively increase the sensitivity of the dominant follicle to FSH, facilitating monofollicular growth.

Chorionic Gonadotropin↗

PubMed1999

Bromocriptine-induced premature oestrus is associated with changes in the pulsatile secretion pattern of follicle-stimulating hormone in beagle bitches.

The secretory profiles of LH and FSH were investigated before and during the administration of bromocriptine in six beagle bitches. Plasma samples were obtained via jugular venepuncture at 10 min intervals for 6 h every 2 weeks until the next ovulation. Bromocriptine treatment was started 100 days after ovulation. Both before and after bromocriptine treatment, LH and FSH pulses occurred together. The mean duration of the FSH pulse (120 min) was significantly longer than that of the LH pulse (80 min). The interoestrous interval in the bitches treated with bromocriptine was significantly shorter than that of the preceding cycle (160 +/- 3 versus 206 +/- 24 days). The mean basal plasma FSH concentration (7.4 +/- 0.6 versus 6.1 +/- 0.7 iu l-1) and the mean area under the curve for FSH (46.6 +/- 4.7 versus 40.4 +/- 4.4 iu l-1 in 6 h) increased significantly after the start of the bromocriptine treatment. In contrast, the differences in mean basal plasma LH concentration (2.1 +/- 0.2 versus 2.0 +/- 0.2 micrograms l-1) and the mean area under the curve for LH (19.0 +/- 3.1 versus 19.5 +/- 2.5 micrograms l-1 in 6 h) between the day before and 14 days after the start of the bromocriptine treatment were not significant. Bromocriptine administration also lowered the mean amplitude of the FSH pulse and shortened the mean duration of the FSH pulse, without influencing the LH pulse. In addition to demonstrating the concurrent pulsatile secretion of LH and FSH, the results of the present study demonstrate that the bromocriptine-induced shortening of the interoestrous interval in the bitch is associated with an increase in plasma FSH concentration without a concomitant increase in plasma LH concentration. This finding indicates that treatment with the dopamine agonist bromocriptine increase plasma FSH to a concentration that results in the enhancement of follicle development.

Analysis of Variance↗

PubMed1998

Follicle-stimulating hormone measured in unextracted urine: a reliable tool for easy assessment of ovarian capacity.

OBJECTIVE: To determine the presence of FSH in unextracted urine of perimenopausal women using a microparticle enzyme immunoassay kit on an AxSYM random access immunoassay analyzer. DESIGN: Controlled descriptive study. SETTING: A large teaching hospital and infertility clinic. PATIENT(S): Forty perimenopausal women aged 32-55 years admitted to our clinic for a gynecological operation. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Mean serum FSH level and urinary FSH in early-morning urine, in a random void urine sample, and in 24-hour urine on the same day. FSH in urine on the day of excretion and 1 and 4 weeks thereafter, stored under various conditions. FSH in urine before and after extraction. RESULT(S): The Pearson's correlation coefficient between mean serum FSH levels and urinary FSH in early morning urine was 0.904, in a random void 0.915, and in 24-hour urine 0.857. Determination of optimal storage conditions revealed that urine was best kept at 4 degrees C without any additive. The correlation between FSH in extracted and unextracted urine was 98.9%. CONCLUSION(S): In perimenopausal women, FSH can be reliably measured in unextracted urine. The correlation between urinary FSH and a random void urine sample and mean FSH from a serial serum sample is very high. Urine can be stored for 4 weeks at 4 degrees C without loss of FSH immunoreactivity.

Adult↗

PubMed1998

Apoptotic cell death in human granulosa-lutein cells: a possible indicator of in vitro fertilization outcome.

OBJECTIVE: To determine whether women who do not conceive during an IVF treatment despite normal FSH levels have a higher rate of apoptosis in their granulosa-lutein cells than women who do conceive. DESIGN: Prospective. SETTING: Large teaching hospital and fertility center. PATIENT(S): Patients with normal FSH levels undergoing an IVF treatment. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Outcome of the IVF treatment and percentage of apoptotic granulosa-lutein cells. RESULT(S): A significantly lower percentage of granulosa-lutein cells were apoptotic in patients who became pregnant compared with those who did not become pregnant. A higher basal FSH level was significantly correlated with the duration of the stimulation, and the number of follicles was significantly inversely correlated with the number of ampules of FSH used and the duration of the treatment. The number of embryos was significantly correlated with the number of oocytes, and significantly inversely correlated with the number of apoptotic granulosa-lutein cells. CONCLUSION(S): Fewer granulosa-lutein cells are apoptotic in women who have an ongoing pregnancy after IVF treatment than in women who do not conceive.

Adult↗

PubMed1998

Higher risk of preeclampsia in the polycystic ovary syndrome. A case control study.

OBJECTIVE: To determine whether the risk of pregnancy-induced hypertensive disorders (PIHD) is higher in patients with the polycystic ovary syndrome (PCOS) than in non-PCOS controls, matched for age and parity. STUDY DESIGN: Retrospective analysis of eighty-one patients with PCOS, consecutively becoming pregnant during a seven-year period. Each PCOS-patient was matched for age and parity with one control patient. Chi-squared, Mann-Whitney or Fisher's exact-tests were used for statistical analysis. RESULTS: Overall incidence of PIHD was similar in both study groups. However, incidence of preeclampsia was significantly higher in patients with PCOS than in controls (P = 0.02). This higher incidence can not be explained by body mass index, endocrine profile before pregnancy, induction of ovulation or treatment regimens. CONCLUSIONS: PCOS-patients are at a significantly higher risk for preeclampsia than non-PCOS controls.

Adult↗

PubMed1998

Insulin-like growth factor (IGF)-I and IGF binding protein-3 concentrations in fluid from human stimulated follicles.

Insulin-like growth factor-I (IGF-I) and IGF binding protein-3 (IGFBP-3) play an important role in regulating follicle growth and maturation. We have evaluated whether responsiveness to gonadotrophins during an in-vitro fertilization (IVF) treatment is related to follicular fluid IGF-I and IGFBP-3 concentrations. We also investigated if a difference is present in IGF-I and IGFBP-3 concentrations between patients treated with human menopausal gonadotrophin (HMG) and patients treated with highly purified follicle stimulating hormone (FSH). We have measured IGF-I and IGFBP-3 in follicular fluid from pre-ovulatory follicles in an IVF programme. All 70 patients were stimulated after being down-regulated with a gonadotrophin-releasing hormone (GnRH) analogue. IGF-I concentrations in follicular fluid were significantly inversely correlated with the number of ampoules FSH administered and number of days of FSH administration, and significantly correlated with the number of follicles aspirated. IGFBP-3 concentrations were not correlated with any other parameter measured nor were IGF-I and IGFBP-3 concentrations correlated. IGFBP-3 concentrations were significantly higher in patients receiving highly purified FSH compared with patients receiving HMG (P < 0.005). These results are new evidence that IGF-I concentration in follicular fluid is higher in women who respond better to follicular stimulation, i.e. women who grow many follicles, women who need a shorter duration of stimulation and women who need fewer ampoules FSH before oocyte retrieval.

Adult↗

PubMed1998

Octreotide, a somatostatin analogue, alters ovarian sensitivity to gonadotrophin stimulation as measured by the follicle stimulating hormone threshold in polycystic ovary syndrome.

The aim of the present study was to determine the effect of octreotide, a somatostatin analogue, on ovarian sensitivity for follicle stimulating hormone (FSH) in patients with polycystic ovary syndrome (PCOS). As the measure of ovarian sensitivity, the FSH threshold was determined in a case-control set-up. Eleven patients with PCOS were treated with FSH in a low dose step-up manner and subsequently received treatment with FSH combined with octreotide. The FSH threshold was found to be significantly higher during combined treatment. This increase was associated with a decrease in insulin-like growth factor-I (IGF-I) and IGF binding protein-3 (IGFBP-3) concentrations during treatment with octreotide, but not with a decrease in insulin concentrations. No differences were found between the two regimens, in number of follicles, in oestradiol concentrations on the day of human chorionic gonadotrophin (HCG) administration or in ovulation rate. With both treatments, there was a very low rate of multifollicular development. It can be concluded that octreotide lowers ovarian sensitivity for FSH through suppression of IGF-I/IGFBP-3 in patients with PCOS. However, this does not appear to affect follicular development during gonadotrophin stimulation, because the latter is controlled to a high degree by the use of a low dose step-up treatment schedule in these patients.

Adult↗

PubMed1998

Relationship of the menstrual cycle pattern in 14-17 year old old adolescents with gynaecological age, body mass index and historical parameters.

In a cross-sectional population-based study the association between the menstrual pattern in ninth grade schoolgirls and calendar age, gynaecological age, body mass index (BMI) and historical parameters was investigated. The survey was held in a combined urban and rural region, south of Amsterdam. A total of 2480 adolescents, mean age 15.3 +/- 0.6 (SD) years, answered a questionnaire: response 92%. The menstrual cycle patterns were categorized to regular menstrual cycles (RMC), irregular menstrual cycles (IMC), oligomenorrhoea, polymenorrhoea, pre-menarche, <6 months after menarche, and oral contraceptive use. Gynaecological age was strongly associated with the prevalence of IMC but only weakly with the prevalence of oligomenorrhoea. In a logistic regression analysis gynaecological age, subjective acne and intellectual performance were independently associated with oligomenorrhoea. Gynaecological age, low BMI, chronic non-specific lung disease (CNSLD) or allergic disease, stress and strain, weight loss of >5 kg were independently associated with IMC. More than 8 h sports per week was associated with not having experienced menarche in the ninth grade but not with menstrual cycle disturbances. The association between CNSLD or allergic disease and IMC has not previously been described. The associations between weight loss, low body weight, stress, physical exercise or signs of hyperandrogenism and menstrual cycle patterns in adolescents are weak when studied on a population basis. The value of these parameters to explain abnormal menstrual cycle patterns is limited.

Adolescent↗

PubMed1998

Gonadotrophin-releasing hormone agonist dose-dependency of pituitary desensitization during controlled ovarian hyperstimulation in IVF.

The aim of this study was to find the minimal effective daily s.c. dose of the gonadotrophin-releasing hormone (GnRH) agonist, triptorelin acetate, that suppresses the GnRH-induced release of luteinizing hormone (LH) at time of human chorionic gonadotrophin (HCG) injection and thereby prevents spontaneous LH surges during in-vitro fertilization (IVF) stimulation cycles. Therefore, a double-blind, prospective and randomized titration study was performed. A total of 48 IVF patients were divided into four groups of 12 patients. Each group received a different dose of triptorelin acetate, namely 5, 15, 50 or 100 microg s.c. daily. Standard ovarian stimulation was carried out using urinary follicle stimulating hormone (FSH) preparations. A 500 microg GnRH test was performed 90 min before the HCG injection in order to measure the degree of pituitary desensitization. Spontaneous LH surges were not detected in any of the groups, although three patients in the 5 microg group had ovulated at the time of ovum retrieval. The pituitary LH response to the GnRH test at time of HCG, expressed as area under the curve (AUC), appeared to be dose-dependent. Thus, a daily s.c. dose of 100 microg triptorelin acetate appears to be too high, since adequate desensitization of the pituitary (i.e. no spontaneous LH surge) can be achieved with doses as low as 15 and 50 microg.

Chorionic Gonadotropin↗

PubMed1998

Predictive value of serum follicle-stimulating hormone levels in the differentiation between hypogonadotropic hypogonadism and constitutional delay of puberty.

OBJECTIVE: Gonadotropin secretion was evaluated to predict hypogonadotropic hypogonadism (HH) in 36 children suspected of having HH. METHODS: LH was measured for 24 h at 10-min intervals, and FSH and estradiol or testosterone at 1-hour intervals. Twenty boys (age 15.7, range 13.2-19.3 years) and 16 girls (age 16.1, range 13.0-20.6 years) were studied. RESULTS: LH pulses were detected in 9 boys and 5 girls. HH was confirmed in all 11 LH apulsatile boys and in 8 of 11 LH apulsatile girls. Random FSH values of < or =1.11 and < or =2.86 IU/l in boys and girls, respectively, discriminated patients with LH pulses from patients without (sensitivity for lack of LH pulses 97 and 100%, respectively). In boys testicular volume was not discriminatory. In 1 girl LH pulses were observed without estradiol production, suggesting LH neurosecretory dysfunction. CONCLUSIONS: Low FSH levels in adolescence are strongly related to a lack of LH pulses. Lack of LH pulses is highly suspect for HH. FSH may be a tool in the differentiation between HH and delayed puberty.

Adolescent↗

PubMed1998

Increased levels and pulsatility of follicle-stimulating hormone in mothers of hereditary dizygotic twins.

According to the endocrine model of hereditary dizygotic twinning, high FSH is responsible for multiple ovulation and pregnancy. Our study explored the underlying neuroendocrine causes. In a prospective clinical study, we compared the third day of menses parameters of episodic secretion of LH and FSH, the pituitary response to LHRH, plasma estradiol, and dimeric inhibin A and B in 16 regularly menstruating and 9 postmenopausal mothers of dizygotic twins with a family history of twinning and 14 premenopausal and 9 postmenopausal controls. Seven of 16 premenopausal mothers of twins had abnormally high FSH levels of more than 10 IU/L compared with 1/14 in controls (P = 0.024). In the premenopausal mothers of twins, mean FSH concentrations (P = 0.025) and FSH pulse frequency (P = 0.003) were significantly elevated, whereas FSH pulse amplitude and FSH response to LHRH were unaltered. For LH, neither the secretory parameters nor the response to LHRH was different. There were no differences between estradiol and inhibin A and B levels. Postmenopausal mothers of twin and controls did not differ with respect to the secretory pattern of LH and FSH. We conclude that under equal ovarian feedback conditions, premenopausal mothers of a dizygotic twin have hyper stimulation by endogenous FSH caused by neuroendocrine, hypothalamic, or pituitary mechanisms. This is the result of altered responsiveness to ovarian feedback and/or pituitary or suprapituitary, non-LHRH-like mechanisms that stimulate pulsatile FSH.

Adult↗

PubMed1998

Cohort size rather than follicle-stimulating hormone threshold level determines ovarian sensitivity in polycystic ovary syndrome.

The aim of the presented study was to compare FSH threshold levels and ovarian response to stimulation with one of two standard increments of exogenous FSH above the threshold in patients with polycystic ovary syndrome (PCOS) (n = 12) and eumenorrheic women (n = 11). The individual FSH threshold was determined by treatment according to a low-dose, step-up protocol with urinary FSH (Metrodin; Ares Serono, Geneva, Switzerland). In a subsequent treatment cycle, six PCOS patients and six eumenorrheic women were randomly assigned to double-blind treatment with the threshold dose plus 1/2 ampoule; the other six PCOS patients and five eumenorrheic women were treated with 1 ampoule above the threshold dose. Determination of threshold levels showed no significant differences in median and range between PCOS patients and eumenorrheic women. The number of follicles on the day of human chorionic gonadotropin administration showed no significant correlation with the increase in FSH level above the threshold level. Irrespective of the dose given, the number of follicles in the PCOS group was significantly higher than in eumenorrheic women. The higher sensitivity for gonadotropin stimulation in patients with PCOS compared with women with regular menstrual cycles therefore appears not to be dependent on differences in FSH threshold level, but rather on the larger size of the FSH sensitive cohort of small antral follicles.

Adolescent↗