Biomedical subjects
Publications and source records attributed to M H van Hooff.
In a term pregnant woman vaginal blood loss and a protruding tumour in the vulva were caused by extreme oedematous swelling of the anterior labium of the cervix.
Recent publications have reported a relation between a decreased ovarian reserve and Down's syndrome pregnancies. Using the data of a case-control study into risk factors for a Down's syndrome pregnancy, we estimated the usefulness of pre-conceptional basal follicle stimulating hormone (FSH) screening (detection rate, false positive rate, positive and negative likelihood ratio, as well as the loss rate of unaffected pregnancies) to identify Down's syndrome pregnancies. The optimal detection rate of pre-conceptional basal FSH screening for Down's syndrome pregnancies was 14%, corresponding to a false positive rate of 5% and a positive likelihood ratio of 2.8. Incorporation of basal FSH screening into the regimen of first trimester serum screening followed by nuchal translucency measurement would increase the detection rate from 85 to 87%. However, basal FSH screening alone or in combination with other screening methods would cause an unacceptably high loss rate of unaffected pregnancies compared with current screening protocols, indicating that routine pre-conception basal FSH screening would not be useful to identify women at risk for a Down's syndrome pregnancy. However, when elevated basal FSH concentrations are diagnosed during subfertility evaluation, an elevated risk for a Down's syndrome pregnancy could be discussed with women who become pregnant.
OBJECTIVE: To assess the predictive value of elevated basal FSH concentrations during the initial subfertility workup with respect to fecundity in a general subfertility population with ovulatory menstrual cycles. DESIGN: Nested case-control study. SETTING: Fertility center of a university hospital. PATIENT(S): Fifty subfertile women with basal FSH levels >10.0 IU/L and 50 age-matched controls. INTERVENTION(S): Long-term follow-up (3-7 years). MAIN OUTCOME MEASURE(S): Pregnancies, deliveries, and time to pregnancy. RESULT(S): Patients with elevated basal FSH levels and controls were comparable with regard to basic characteristics, clinical diagnoses, and subfertility treatment. Long-term follow-up showed that 52% of the women with elevated basal FSH concentrations became pregnant (positive predictive value 48%) versus 62% of the controls, and 42% versus 46% eventually delivered a child, respectively. The mean time to pregnancy was 3.0 years in the elevated-FSH group and 3.4 years in controls. Most of the pregnancies in both groups occurred after spontaneous conceptions. CONCLUSION(S): The results of this study suggest that screening for elevated basal FSH concentrations is of no additional value in a general subfertility population with ovulatory menstrual cycles.
STUDY OBJECTIVE: To evaluate the possible role of inappropriate LH secretion, hyperandrogenism, and hyperinsulinemia in the development of polycystic ovaries (PCO) and the polycystic ovary syndrome. DESIGN: Observational. SETTING: General population samples. PARTICIPANTS: 58 adolescents with regular menstrual cycles, 50 with irregular menstrual cycles, and 29 with oligomenorrhea (age 16.7+/-0.9 years). INTERVENTIONS: Transabdominal pelvic ultrasonography and vena puncture. MAIN OUTCOME MEASURES: PCO; LH, androstenedione, and testosterone levels; overnight fasting insulin concentrations; and oligomenorrhea. RESULTS: The prevalence of PCO increased significantly with the irregularity of the menstrual cycle pattern, as illustrated by the study, finding PCO in 9% of the girls with regular menstrual cycles, 28% of those with irregular menstrual cycles, and 45% of oligomenorrheic girls. The LH and androgen concentrations were significantly higher in girls with PCO; the insulin levels and the glucose-insulin ratio did not differ when the girls with PCO were compared with girls with normal ovaries. Oligomenorrheic girls with PCO had the highest androgen and LH concentrations; their insulin concentrations and glucose-insulin ratio were in the same range as girls with regular menstrual cycles and normal ovaries; and both their hip and waist girths were wider, although their waist-hip ratio was normal. CONCLUSIONS: PCO in adolescents is associated with irregular menstrual cycles, oligomenorrhea, and/or high androgen and LH levels; but no relationship was found with the insulin level or glucose-insulin ratio. Thus, it is doubtful that hyperinsulinemia is an important factor in the development of PCO or polycystic ovary syndrome.
Data on changes in hormone concentrations during the first years after menarche are scarce. We studied the relation between gynecological age (age minus age at menarche), hormone concentrations, and body measurements from the lst to the 6th yr after menarche in 229 observations of girls with regular menstrual cycles, 157 observations of girls with irregular menstrual cycles, and 104 observations of girls with oligomenorrhea. Body Mass Index, waist circumference, hip circumference, LH, androstenedione, testosterone, and dehydro-epiandrosterone sulphate increased significantly (linear regression, P < 0.05) by gynecological age in all menstrual cycle pattern groups. For PRL and estradiol a significant increase with gynecological age was only documented in the regular menstrual cycle group and for waist to hip ratio only in the irregular menstrual cycle group. No significant correlation could be documented between gynecological age and overnight fasting insulin concentrations or glucose to insulin ratio. We found no significant correlation between insulin concentrations or glucose to insulin ratio and androgen concentrations. Significant positive correlations were found between LH and androgens. LH and androgen levels increase during the first years after menarche, and reference values should be adjusted for gynecological age. In these years, no significant correlation between hyperinsulinemia and hyperandrogenemia could be documented.
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.
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.
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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.
BACKGROUND: Oral contraceptives are prescribed as contraception but also as therapy for menstrual cycle disturbances and acne. We studied the prevalence of oral contraceptive (OC) use and the indications to start OC use among adolescents. METHODS: A cohort consisting of ninth grade secondary school girls (mean age 15.3+/-0.6 (s.d.) years) answered a questionnaire on their menstrual cycle. OC users were asked about duration and reasons for OC-use and the name of the preparation they used. The influence of calendar age, gynecological age and level of education on the prevalence of OC was studied by multiple logistic regression analysis. RESULTS: The response on the questionnaire was 92%. Of 2248 responders 248 (11%) used oral contraceptives: 74% used low dose 'sub 50' preparations, 3% pills with 50 microg estrogen, 3% tri-phase preparations and 17% pills with antiandrogens. Of girls aged 14, 15 and 16 years 4%, 12% and 28% respectively, used OC. Of the 15-year-olds 31% mentioned contraception as most important reason for OC use, 18% menstrual cycle irregularity, 26% dysmenorrhea, 10% acne and 5% other reasons. Calendar age, gynecological age and level of education were independent variables for OC use in general and for OC use for contraception or dysmenorrhea, but less so for OC use for menstrual cycle irregularity or acne. CONCLUSIONS: During adolescence low dose OC's were frequently used. In The Netherlands OC use among girls aged 15 and 16 years doubled in comparison with 1982. One third of the adolescent OC-users mentioned contraception as most important reason to start OC. Gynecological age (a determinant of biological maturation), calendar age (a determinant of biological maturation and lifestyle in peer groups), and level of education (a determinant of lifestyle in peer groups) were associated with OC use.
OBJECTIVE: To describe frequency of oral contraceptive (OAC) use, indications for OAC use and influence of calender age, gynaecological age (age minus age at menarche) and level of education on OAC use among ninth grade secondary school girls. SETTING: Secondary schools in Amstelland-de Meerlanden, a combined urban and rural region to the south of Amsterdam. METHOD: By questionnaire and individual interview on menstrual cycle pattern and OAC use, school girls were asked about duration and reasons for OAC use and what preparation they used. RESULTS: The response to the questionnaire was 92%, that to the interview 83%. Of the 2248 responders 248 (11%; mean age 15.3 years (SD: 0.6)) used OAC: 74% used low dose 'sub 50' preparations, 3% pills with 50 micrograms oestrogen, 3% 3-phase preparations and 17% pills with antiandrogens. Of girls aged 14, 15 and 16 years 4%, 12% and 28%, respectively, used OAC. Of the 15-year-olds 36% mentioned contraception as most important reason, 20% menstrual cycle irregularity, 28% dysmenorrhoea, 12% acne and 5% other reasons. With multiple logistic regression analysis age, gynaecological age and level of education were independent variables for OAC use in general and for OAC use for contraception or dysmenorrhoea, but less so for OAC use for menstrual cycle irregularity or acne. CONCLUSION: During adolescence low dose OACs are frequently used. Of adolescent OAC users 36% mentioned contraception as most important reason. OAC use in the Netherlands among girls aged 15 and 16 years doubled in comparison with 1982. Gynaecological age and calender age (determinants of biological maturation), and level of education (a determinant of life style) were associated with OAC use.
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In view of cellular immunotherapy with cytotoxic monocytes in minimal residual leukemia we have studied the effects of monocytes on the growth and survival of leukemic cells from cell lines and from patients with acute myeloid leukemia (AML). Using highly purified and interferon-gamma (IFN gamma) activated human monocytes, monocyte-mediated cytotoxicity (MMC) was evaluated in an MTT-based colorimetric cytotoxicity assay against six human leukemic cell lines (U937, THP1, KG1, K562, HL60, and 1,25(OH)2D3 differentiated HL60 cells) and cells from AML patients. Leukemic cells from cell lines with an immature phenotype were found to be resistant to MMC, whereas leukemic cells with a more mature and monocytic phenotype were sensitive. This paralleled the sensitivity to tumor necrosis factor-alpha (TNF-alpha). AML cells from patients with an immature phenotype (FAB-M1/M5A) were significantly less sensitive to MMC as compared to more mature AML cells (FAB-M2/M4/M5B). The growth stimulatory effects of non-activated monocytes on immature AML cells could be abrogated in the presence of IFN gamma or IL-3 and GM-CSF. In addition, these cytokines further potentiated MMC, preferentially affecting cells with a more mature phenotype. AML cells with an immunologically immature phenotype (CD34(high), HLA-Dr(low), CD13(low), CD14(low)) were revealed as the least sensitive cells to MMC. The growth stimulatory effects of IL-3/GM-CSF with or without TNF-alpha on AML cells correlated with resistance to MMC. In addition, the cytolytic effects of TNF-alpha in the presence of IFN gamma correlated with an increased susceptibility of AML cells to MMC. In conclusion, our data strongly indicate that MMC is related to maturation in AML, which is correlated to the differential stimulatory and cytolytic effects of monocyte-derived cytokines such as IL-3, GM-CSF, and TNF-alpha.
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The effect of doubling the human menopausal gonadotrophin (HMG) dose in the same treatment cycle in which the ovarian response after 5 days of ovarian stimulation with 225 IU/day is 'low', has been evaluated in a prospective randomized study. Forty-six patients met the ultrasound and oestradiol criteria for enrollment in the study, one patient participated twice. In 22 patients treatment was continued with 225 IU HMG/day and in 25 patients the HMG dose was increased to 450 IU/day. No effect of doubling the HMG dose was found on the length of the ovarian stimulation, peak oestradiol values, number of follicles > or = 11 and > or = 14 mm in diameter respectively on ultrasound on the day of HCG administration, number of cancelled cycles, number of oocytes at follicular puncture and the number of patients with < or = 3 oocytes at retrieval. It is concluded that doubling the HMG dose in the course of an IVF treatment cycle is not effective in enhancing ovarian response in low responders. This is in accordance with current theories on follicular growth, which state that follicular recruitment occurs only in the late luteal and early follicular phase of the menstrual cycle.
The possibilities and limitations of basal body temperature (BBT) records as an adjunct in the management of infertility were re-evaluated. To assess its accuracy as an index of ovulation, 172 charts were analyzed by three different physicians. While the average true positive rate was 90%, the false negative rate was only 2%. The remaining graphs (8%) were classified as non-interpretable, probably reflecting measurement problems. Retrospective assessment of 210 biphasic records showed the thermal nadir to occur within 1 day of the urinary luteinizing hormone (LH) surge in 75% of the cases, and in 90% when 2 days where considered. This confirms BBT as a relatively accurate guide for retrospective identification of the periovulatory period. Moreover, results of a study conducted to investigate how patients experienced daily recording of BBT graphs suggest that the method is well accepted by a high proportion of women. From all these it appears that there are many indications where BBT graphs can still be applied. Development of new electronic devices may further improve the reliability, acceptability and applications of the BBT records in the fertility investigation.