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J Schoemaker

Publications and source records attributed to J Schoemaker.

At least 109 records · Page 6Linked to original sources

Endocrinology of gonadotropin-releasing hormone induced cycles in hypothalamic amenorrhea: the role of the pulse dose.

OBJECTIVE: To find the treatment regimen giving a maximum chance of ovulation and a minimal chance of multiple follicular development in pulsatile gonadotropin-releasing hormone (GnRH) therapy in patients with hypothalamic amenorrhea. DESIGN: We propectively studied the endocrinology of cycles induced with 5, 10, and 20 micrograms GnRH pulse doses, randomly assigned per patient, comparing this with the endocrinology of spontaneous menstrual cycles. SETTING: All patients were treated at the Academic Hospital of the Vrije Universiteit, Division of Reproductive Endocrinology and Fertility. PATIENTS: Fifteen patients with hypothalamic amenorrhea were treated for one to three cycles; 14 normally cycling volunteers were studied for one cycle. MAIN OUTCOME MEASURE: Number of ovulations per pulse dose; luteinizing hormone, follicle-stimulating hormone, total urinary estrogens (Es), and pregnanediol were measured per cycle day and per stimulation day. RESULTS: The endocrinology of all ovulatory cycles remained within the normal range. First treatment cycles showed significantly higher ovulation rates compared with subsequent cycles. Significantly more anovulation was observed in cycles with 5-micrograms pulse doses. Luteal Es were significantly higher in induction cycles compared with controls. CONCLUSIONS: The optimum treatment regimen should be to start induction with 5 micrograms/pulse in the first cycle and to raise the dose to 10 micrograms/pulse in subsequent cycles, regardless of the outcome of the first cycle. After ovulation, the pulse interval should be changed to 240 minutes.

Adult↗

A testosterone-producing tumour in the mesovarium.

An androgen-secreting adnexal tumour is presented. The tumour was a steroid cell tumour of the mesovarium, without crystals of Reinke, hence the diagnosis was a steroid cell tumour (lipid cell tumour), not otherwise specified (in this case, because of its location in the mesovarium, an adrenal rest tumour). The clinical presentation, diagnosis, prognosis and differential diagnosis of virilizing adnexal tumours are discussed.

Adnexal Diseases↗

Multiple follicular development in women with normal menstrual cycles treated with pulsatile gonadotrophin-releasing hormone.

In a prospective study, 15 patients with normal menstrual cycles were treated with pulsatile gonadotrophin-releasing hormone (GnRH) for one to four cycles. These cycles were compared to unstimulated cycles of 14 volunteers. There was a surprisingly stable number of large (greater than or equal to 14 mm diameter) follicles per patient. The number of large follicles in induction cycles was significantly greater than in controls (2.4 versus 1.07). This was due to significantly higher follicle stimulating hormone levels during the first days of treatment. Our data provide a rationale for the use of pulsatile GnRH for a safe and mild form of stimulation in assisted reproductive therapies.

Adult↗

A controlled study of human chorionic gonadotrophin induced ovulation versus urinary luteinizing hormone surge for timing of intrauterine insemination.

Forty-eight patients in a programme of intrauterine insemination (IUI) were randomized in a cross-over study. All were stimulated with clomiphene citrate (CC) and inseminated either after follicular rupture induced by human chorionic gonadotrophin (HCG) or after a spontaneous urinary luteinizing hormone (LH) surge. The HCG was administered when follicles of 18-22 mm in diameter were observed on ultrasound and IUI was performed 37-40 h thereafter. The monitoring of a urinary LH peak was carried out using a rapid urinary LH test. IUI took place approximately 22 h after detection of the LH surge. Overall, the pregnancy rates were 9.3% (4/43) after HCG induced ovulation and 20.5% (9/44) after spontaneous ovulation (P = 0.12). Analysis of mid-cycle events showed that following sonographic criteria, the HCG injection was performed significantly earlier in the cycle compared with the spontaneous LH surge. In addition, the mean diameter of the preovulatory follicles was significantly smaller and insemination was substantially earlier in the HCG induced cycles. These findings suggest that a beneficial effect arises from allowing the natural process of final follicular maturation to occur.

Adult↗

Evidence for existence of immunoglobulins that block ovarian granulosa cell growth in vitro. A putative role in resistant ovary syndrome?

The sera of 26 patients with premature ovarian failure were examined in order to detect immunoglobulin-G (IgGs) that can block FSH-induced in vitro granulosa cell DNA synthesis via, a Feulgen cytochemical bioassay system. The IgGs of four patients with polycystic ovary-like disease, five postmenopausal women, and four eumenorrheic women served as controls. Ovarian growth blocking IgGs were found in 21 of the 26 premature ovarian failure (POF) cases. The few cases characterized by the absence of follicles (streak ovaries) and the controls were negative. The ovarian blocking IgGs were far more prevalent in the POF cases than anti-cytoplasmic ovarian antibodies detected by an indirect immunofluorescence assay (only one of the 26 POF patients was positive). Our data hence confirm earlier expressed views that immune mechanisms are involved in a high proportion of patients with POF.

Adult↗

Growth hormone secretion patterns in relation to LH and estradiol secretion throughout normal female puberty.

Pulsatile growth hormone secretion patterns were studied in relation to luteinizing hormone and estradiol release in 33 healthy (pre)pubertal girls. Plasma GH was determined every 10 min, plasma LH and E2 every hour. Night-time GH release was always higher than daytime GH release. During daytime, all GH secretion parameters, except for the basal GH level, increased significantly from the prepubertal stage to stage B4 before (m-) the menarche (p = 0.05) and decreased thereafter (p = 0.05). During night-time, mean GH level and the fraction of GH in pulses also tended to increase from stage B1 to stage B4m-. The number of high pulses (greater than 8 micrograms/l) during day and night together tended to increase until stage B4m- and decreased after the menarche (p = 0.05). Height velocity did not correlate with the number of high pulses (Kendall tau = 0.14, p = 0.14). From stage B1 to B4m- high correlations were observed between E2 levels and GH secretion parameters, particularly during the day (tau = 0.59-0.71, p less than or equal to 0.01). The correlations between LH levels and GH secretion were high as well (tau = 0.50-0.81, p less than or equal to 0.01), but equal during day and night. It is concluded that during puberty 1. spontaneous GH release in girls increases 2-3 fold until the menarche and decreases thereafter, primarily as the result of an increasing and decreasing GH pulse amplitude; 2. diurnally increasing estradiol levels correlated with increasing GH secretion.

Adolescent↗

Urinary luteinizing hormone testing and prediction of ovulation in spontaneous, clomiphene citrate and human menopausal gonadotropin-stimulated cycles. A clinical evaluation.

A urinary luteinizing hormone test was utilized to predict ovulation in 99 spontaneous, 122 clomiphene citrate, and 82 human menopausal gonadotropin stimulated cycles. Tests were performed in early morning and evening specimens and follicular development was monitored by daily ultrasonography. A positive detection rate of 98, 97, and 94%, respectively, was obtained. Evidence of luteinized unruptured follicles was seen more frequently in stimulated cycles, concurring with negative test results. In 2 spontaneous, 1 clomiphene citrate and 5 hMG induced cycles two distinct LH surges were detected concomitant with a pattern of follicular atresia and subsequent new follicular development. Most ovulations occurred between 16 and 28 h after LH detection, significantly earlier in spontaneous than in clomiphene citrate stimulated cycles (p less than 0.02), whereas pre-ovulatory follicles were larger in the clomiphene citrate group (p less than 0.001). The mean duration of the follicular and luteal phases, as calculated from the LH peak, was substantially shorter in the hMG cycles than in the other two groups (p less than 0.001).

Adult↗

Neuroendocrine control in polycystic ovary-like syndrome.

In this review article evidence is assembled from the neuroendocrinology of women with polycystic ovary-like syndrome (PCOS), to argue that the central dysregulation of gonadotropin secretion as found in the syndrome is not the cause of its development. The increased amplitude of luteinizing hormone (LH) pulses is explained by an increased pituitary sensitivity to gonadotropin releasing hormone (GnRH) due to prolonged unopposed estrogen exposure of the gonadotropic cells. The increase in pulse frequency cannot be used in the argument because it may be the cause for, as well the result of, the pathological status of the ovary. A good argument for a pathogenetic involvement of central factors, however, is the reversed day/night rhythm in adolescent girls with PCOS. A critical review of the literature does not give evidence of involvement of either obesity or catecholamines in the central abnormalities. Therefore they cannot cause PCOS via central feedback systems. The response of the gonadotropins to progesterone is the same as it is in normally cycling women. Androgens exert a variable effect on LH secretory patterns, although they do induce the typical change of PCOS in the ovaries. This argues for an ovarian rather than for a central cause. Endogenous opiates seem to be increased in PCOS. It can be argued that this should suppress both LH secretion and adrenal androgen secretion. It should also stimulate insulin-like growth factor (IGF)-binding proteins, thereby binding more IGF with less stimulatory action on the theca cells to produce androgens. Therefore endogenous opiates do not seem to be involved in the pathogenesis of PCOS either. Studies in PCOS during the recovery from GnRH agonist treatment show that the luteinizing hormone/follicle stimulating hormone (LH/FSH) ratio is quite normal for some time during the recovery phase. However, PCOS always develops again. This therefore does not give a clue either. In pulsatile GnRH stimulation of PCOS patients, the LH and FSH secretory patterns completely normalize. However, the symptoms of PCOS continue under this stimulation and the clinical pattern does not change dramatically. This gives the best argument that PCOS is caused by one or more peripheral factors, which may be ovarian in origin, rather than by central factors.

Androgens↗

Interpretations of five monoclonal immunoassays of lutropin and follitropin: effects of normalization with WHO standard.

Five mono(oligo)clonal immunometric assays for lutropin (LH) and follitropin (FSH)--bioMérieux, IRE-Medgenix, Serono Diagnostics, Diagnostics Products Corp. (DPC), and LKB--were evaluated in comparison with two polyclonal RIAs (DPC and Amersham). Detection limits varied from 0.04 to 0.32 int. unit/L and 0.06 to 0.86 int. unit/L for LH and FSH, respectively. Intra- and interassay precision (CV) at three concentrations varied from 2.0% to 29.8%, showing that not all kits tested gave acceptable results, especially for LH. Linearity and parallelism were acceptable, except for the DPC FSH kit and the bioMérieux LH kit. High-dose "hook" effects were seen in some kits at LH concentrations of 250 int. units/L, but not in the FSH kits up to concentrations of 350 int. units/L. Reagents in some kits cross-reacted with choriogonadotropin. The clinical validity of the assays was tested in 25 pre- and 25 postmenopausal healthy women and in 66 patients with polycystic ovary disease. In contrast to FSH, LH values varied significantly not only between polyclonal and monoclonal assays but also between the various monoclonal assays, despite the fact that all manufacturers state that their kits are calibrated on the same standards: WHO International Reference Preparation (IRP) 68/40 for LH and 78/549 for FSH. We normalized the results by using new WHO standards: IRP 80/552 for LH and IRP 83/575 for FSH. This decreased significantly the between-kit differences in LH results for individuals. The much-used LH/FSH ratio greater than 3 for diagnosing patients with polycystic ovary disease is not valid when monoclonal assays are used, and is kit-dependent. However, using the normalized results yields a "new" LH/FSH ratio, which is kit-independent and differs significantly between patients and healthy subjects.

Adolescent↗

Exogenous versus endogenous pulses of luteinizing hormone-releasing hormone and secretory patterns of gonadotropins.

OBJECTIVE: Does an exogenously administered regimen of luteinizing hormone-releasing hormone (LH-RH) pulses override endogenous LH-RH? DESIGN: Pulses of LH-RH were given intravenously during 1 week with intervals of 90 (n = 5) or 120 minutes (n = 5). Before, during, and after treatment serial plasma luteinizing hormone (LH) and follicle-stimulating hormone (FSH) patterns and pituitary responsiveness to LH-RH were estimated. PATIENTS: Women with virtual absence of gonadal function (postmenopause, gonadal dysgenesis, and premature menopause). RESULTS: During treatment with the 90-minute interval, no LH pulses that were not related to injections of LH-RH were observed. Two spontaneous LH pulses were observed during treatment with the 120-minute interval. Immediately after treatment, a lowered incidence of spontaneous LH pulses was seen of 3 pulses/6 h if LH-RH had been given every 90 minutes and to 1.5 pulses/6 h after the 120-minute interval treatment. Gonadotropin responses to 100 micrograms of LH-RH were attenuated during treatment but recovered within 48 hours after discontinuation of treatment. CONCLUSIONS: (1) Exogenously administered LH-RH can override endogenous LH-RH or its effects on the release of LH in women with hypergonadotropic hypogonadism; (2) during pulsatile LH-RH treatment desensitization of the pituitary occurs to some degree; and (3) immediately after cessation of treatment with pulsatile LH-RH, spontaneous LH pulses are present but with a significantly lower incidence.

Female↗

Testicular weight, tubular diameter and number of Sertoli cells in rats are decreased after early prepubertal administration of an LHRH-antagonist; the quality of spermatozoa is not impaired.

To suppress gonadotropin secretion during the sensitive period in development of the testes, immature male rats were treated with an antagonist of luteinizing hormone-releasing hormone (LHRH; ORG. 30276) from postnatal days 6-15. Previously, it has been demonstrated that this treatment results in delayed pubertal development, decreased testicular weight, impaired fertility and adult sexual behavior. In the present experiments it was investigated whether the decreased testicular weight was correlated with morphological changes in the testis. Also, by using an artificial insemination technique, the biological activity of spermatozoa of adult male rats, treated during early prepuberty with the LHRH antagonist (LHRH-A), was tested. The present results demonstrated a decrease in the diameter of the testicular tubuli of LHRH-A-treated rats. The number of Sertoli cells per tubular cross-section was also smaller. But qualitatively no differences could be observed in the testis. All stages of maturation of the seminiferous epithelium were equally frequently represented in LHRH-A-treated males compared with controls. Artificial insemination using spermatozoa obtained from the epididymis of LHRH-A-treated rats, resulted in a pregnancy rate of 100%, similar to the control rate. From the present data, we conclude that the infertility in adult male rats, treated with an antagonist to LHRH during prepubertal life, does not result from malfunction in the maturational processes in the germinal cells and the testes as a whole, despite the observation of changes in the testicular morphology. The infertility of LHRH-A-treated male rats can be explained by the observed impairment of sexual behavior. We suggest, that a central action of the antagonist of LHRH when administered to immature male rats may lead to permanent changes in the development of sexual behavior.

Animals↗

Intrauterine insemination does and clomiphene citrate does not improve fecundity in couples with infertility due to male or idiopathic factors: a prospective, randomized, controlled study.

In the present prospective study we compared, in terms of pregnancy rates, the differences between intrauterine insemination (IUI) of in vitro capacitated husband's semen and timed natural intercourse in spontaneous or clomiphene citrate (CC) stimulated cycles. A rapid urinary luteinizing hormone peak detection test was used for timing of ovulation. Forty patients suffering from longstanding infertility of male (n = 17), cervical (n = 2), and idiopathic (n = 21) origin were randomly assigned into four distinct treatment modalities during 4 consecutive cycles. A total of 132 cycles were analyzed. In 35 cycles treated with CC plus IUI, five conceptions were achieved, whereas three pregnancies occurred in 32 inseminated spontaneous cycles. Only 1 patient conceived after timed intercourse in 31 CC stimulated cycles, and no pregnancy resulted from 34 spontaneous cycles combined with timed intercourse. There was a statistically significant higher conception rate in cycles in which IUI was performed, whereas the use of CC does not seem to improve the pregnancy rate. Analysis of results for other modifying factors did not substantially affect the relative risk (odds ratio) of pregnancy.

Adult↗

Luteinizing hormone and follicle stimulating hormone secretion patterns in girls throughout puberty measured using highly sensitive immunoradiometric assays.

Pulsatile gonadotrophin secretion patterns were studied in 36 healthy girls by measuring every 10 min and applying immunoradiometric assays (IRMA). Different stages of puberty were associated with significant changes in the plasma LH and FSH levels, pulse numbers (Pno) and pulse amplitudes (pA). Plasma LH was not detectable by day or night in young prepubertal girls (B1), neither was plasma oestradiol (E2); however, plasma FSH was detectable in a pulsatile pattern. In the older prepubertal girls (B1-onset) a discrete pulsatile LH pattern became detectable only during the night; plasma FSH tended to rise, while E2 became just detectable. In the early pubertal girls (B2) most daytime LH values were above the detection limit, in some with low-amplitude pulses. At night, pulses with a wide range of pulse amplitudes were detected. Plasma FSH increased further, plasma E2 only slightly. With the progression of puberty the plasma LH and FSH levels, Pno and pA increased significantly from stage B2 to B3 during the day (P less than or equal to 0.05) and close to significance during the night (0.05 less than or equal to P less than or equal to 0.1). However, in stage B4 the secretory characteristics tended to decline, while from stage B3 onwards plasma E2 started to rise rapidly (P less than or equal to 0.05, during the night from stage B2 to B3, during the day from B3 to B4m-). Simultaneous LH and FSH pulses were observed throughout puberty, usually during the night. Using these IRMA methods nocturnal LH in older prepubertal girls and both diurnal and nocturnal FSH pulsatility could be demonstrated in young prepubertal girls. From this study we conclude that (1) puberty in girls, as in boys, may be brought about by an increasing GnRH secretion both in frequency and amplitude, first appearing during the night. This increased GnRH stimulation results in LH secretion only during the night; (2) a cyclical pulsatile LH pattern including an LH surge can be established before the menarche; the capacity for positive feedback activity is not the final maturation characteristic to achieve an ovulatory menstrual cycle.

Adolescent↗

Sexual precocity induced by ovarian follicular cysts. Is autoimmunity involved?

A 2-year-old girl presented with gonadotrophin-independent precocious puberty due to ovarian follicles. Central precocious puberty was excluded by several GnRH-tests and overnight LH sampling. There were no signs of McCune-Albright syndrome. An ovarian tumour was excluded by laparotomy and biopsies. Abdominal sonography demonstrated follicles occurring mostly in the left, sometimes in the right, ovary. Immunoglobulin G (IgG) purified from the patient's serum was capable of stimulating DNA synthesis in granulosa cells of rat ovarian segments kept in organ culture. Since FSH had a similar in-vitro action it is hypothesized that this patient's IgG mimics the action of FSH.

Animals↗

Deoxyribonucleic acid cytophometry on rat ovarian follicles kept in organ culture: the effects of gonadotropins and plasma from normal, hypergonadotropic menopausal, and hypogonadotropic women.

Pituitary FSH as well as urinary FSH were found to be potent stimulators of in vitro granulosa cell DNA synthesis in Wistar rat ovarian segments kept in organ culture. Optimal responses were reached at the highest concentration used (pituitary FSH, 5 mU/mL: urinary FSH, 50 mU/mL). hCG also appeared to be a potent stimulator (optimal response, 5 mU/mL). LH showed no stimulating effect, but the hormone had a potentiating effect on FSH-induced DNA synthesis. Plasma samples of five normally menstruating women obtained at different stages of the follicular phase were also added to the rat ovarian culture system. All samples stimulated DNA synthesis, but the plasma samples obtained in the late follicular phase showed stronger growth responses, reaching optimal values at lower concentrations compared to the potency of plasma obtained in the early follicular phase (10(-3)-10(-5) vs. 10(-2)-10(-3) mL, respectively). The strong bioeffect of late follicular phase plasma could partly be explained by the potentiating effects of plasma LH on FSH-induced DNA synthesis. When plasma samples of five hypergonadotropic amenorrheic women were added to the culture system, 4 stimulated DNA synthesis moderately, with an optimal growth response at plasma concentrations of 10(-4)-10(-3) mL. When 10 plasma samples of hypogonadotropic amenorrheic women were added to the culture system, 8 had no effect on DNA synthesis, and clear discrepancies were evident between the low to absent ovarian growth potential of the plasma and the practically normal immunoreactive plasma FSH measured by RIA and immunoradiometric assay. These discrepancies may be the effect of nonimmune or immune factors interfering with FSH-induced growth or the effect of molecular changes in the FSH molecule (isoforms).

Adrenocorticotropic Hormone↗

Growth hormone secretion patterns in relation to LH and testosterone secretion throughout normal male puberty.

Pulsatile growth hormone secretion patterns were studied in relation to LH and testosterone release in 30 healthy prepubertal boys and 2 adult men. Plasma GH was measured every 10 min, plasma LH and testosterone every hour. Night-time GH secretion parameters were 2-3 times higher than daytime values. During daytime, mean GH level and the fraction of GH in pulses increased from Tanner stage G2 to G4 (p = 0.01); during night-time these parameters increased as well (p less than or equal to 0.1) and decreased from stage G5 to adulthood (p = 0.05). GH pulse number did not increase; the number of high-amplitude (greater than 8 micrograms/l pulses, however, increased from stage G2 to G4 (p = 0.05) during the day. Height velocity correlated with their number of high pulses during day and night (tau = 0.39, p less than 0.003). From stage G2 to G4 significant correlations were observed between nocturnal testosterone levels and GH secretion parameters (tau = 0.53-0.57), in contrast to nocturnal LH levels. It is concluded that during puberty 1. GH secretion increases as a result of an increased pulse amplitude; 2. there is no consistent correlation between GH and LH levels; 3. increasing nocturnal testosterone levels are correlated with the increasing GH secretion; therefore GnRH does not seem to influence GH secretion directly, but an indirect effect via testosterone is more conceivable, and 4. height velocity is correlated with the number of high GH pulses.

Adolescent↗