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Biomedical subjects

R Vihko

Publications and source records attributed to R Vihko.

At least 127 records · Page 7Linked to original sources
PubMed1984

Effects of metoclopramide-induced hyperprolactinemia during early follicular development on human ovarian function.

Nine healthy women, aged 25 to 36 yr, were treated with metoclopramide (MC) (10 mg orally three times daily) from the first to the sixth day of their cycle (treatment A) for two successive cycles (n = 18) and six of these women later received MC from -3 to the fifth day of the menstrual cycle (treatment B) during one or two cycles (n = 10), to investigate the effects of hyperprolactinemia during the early phase of ovarian follicular growth. Comparisons were performed with control cycles in the same women. The treatment cycles were characterized by low serum concentrations of LH during the early follicular phase and at midcycle, low early follicular phase serum testosterone (T) levels and high luteal phase T and free T index values, with no significant differences between A and B treatment modalities. We classified the treatment cycles into two categories, seriously disturbed and normal or only slightly disturbed, on the basis of ultrasonographic findings and midcycle estradiol (E2) and luteal phase progesterone (P) concentrations. Folliculogenesis was seriously disturbed in 11 of the 28 treatment cycles (39%). During these cycles, midcycle serum LH and the LH to FSH ratio were lowered, luteal phase LH and FSH increased, midcycle E2 and luteal phase P and the P to E2 ratio decreased, luteal phase T and the free T index and androstenedione increased, and luteal phase 5 alpha-dihydrotestosterone decreased. During the early follicular phase and at midcycle the ratios of T to E2 and androstenedione to E2 were increased, and at midcycle and during the luteal phase of the cycle the ratio of T to 5 alpha-dihydrotestosterone was increased. These changes in steroid hormones were probably of ovarian origin since the serum concentrations of dehydroepiandrosterone sulfate and sex hormone-binding globulin were similar in seriously disturbed and control cycles. Four of the nine study subjects were hyperprolactinemia sensitive (disturbed folliculogenesis) and five hyperprolactinemia resistant (no disturbance in folliculogenesis). During the control cycles the hyperprolactinemia-sensitive women had significantly higher serum concentrations of T than the other women. The present observations indicate that hyperprolactinemia may impair the development of the ovarian follicles during their recruitment period, especially in women with relatively high serum T levels.

Adult↗
PubMed1984

Serum sex hormone-binding globulin during puberty in girls and in different types of adolescent menstrual cycles.

Serum sex hormone binding globulin (SHBG) concentrations were measured by an immunoradiometric assay, as part of a longitudinal study of puberty in girls, and were related to age, pubertal stage, age at menarche, weight, nature of the menstrual cycle and serum concentrations of sex steroids. A slow but very significant decrease was seen in SHBG from 77 nmol/l at 8-10 years of age to about 50 nmol/l after 15 years of age. Serum SHBG concentrations showed weak negative correlations with those of androstenedione and testosterone during puberty. The closest associations found between SHBG and the parameters measured were negative correlations with weight and body fat percentage in both pre-menarcheal and post-menarcheal girls, even after the effect of age was accounted for by calculating partial correlation coefficients. Girls who experienced early menarche (before 13.0 years) had lower SHBG but higher oestradiol serum concentrations at 10.0-15.9 years of age compared to girls with later menarche. In ovulatory menstrual cycles, a significant increase in SHBG was found from the early to the late part of the cycle, whereas no changes took place in anovulatory cycles. Serum concentrations of SHBG showed positive correlations with those of oestradiol and progesterone in specimens taken in the late part of the cycle. In view of the weak relationships between serum SHBG and sex steroid concentrations, and the strong relationships between SHBG, weight and body fat percentage, factors other than steroids have to be considered in the regulation of SHBG levels during puberty.

Adolescent↗
PubMed1984

Cytosol estrogen and progestin receptor concentrations and 17 beta-hydroxysteroid dehydrogenase activities in the endometrium and endometriotic tissue. Effects of hormonal treatment.

Concentrations of cytosol estrogen (ERc) and progestin (PRc) receptors and the activities of 17 beta-hydroxysteroid dehydrogenase (17-HSD) were measured in 80 untreated and 23 danazol-treated endometriotic tissue specimens. The results were compared with those obtained from endometrium specimens prior to or following danazol or medroxyprogesterone acetate (MPA) treatment. The concentrations of ERc and PRc in the endometriotic tissue were lower than corresponding values in the endometrium. Cytosol female sex steroid receptors were always present in the normal endometrium, whereas only 70% of the endometriotic lesions were simultaneously ERc- PRc-positive (receptor concentration greater than or equal to 3 and greater than or equal to 6 fmol/mg cytosol protein respectively), 24% PRc-positive, and 6% receptor-negative. In the endometriotic tissue, the mean concentrations of PRc during the luteal phase of the cycle (90 +/- 23, SE, fmol/mg protein) were lower (p less than 0.05) than during the follicular phase (177 +/- 32 fmol/mg protein), while the ERc concentrations and 17-HSD activities did not show any cyclic variations. Danazol and MPA had similar effects on the endometrium, both inducing a decrease in concentration of the female sex steroid receptors and an increase in activity of 17-HSD during short-term treatment (one week), and a decrease in activity of the enzyme during long-term treatment (3 weeks). The effect of danazol on the endometriotic tissue differed from that found in the endometrium. Danazol did not alter the activity of 17-HSD or the concentration of PRc but tended to increase the concentration of ERc in endometriotic tissue when given for 7-30 days.(ABSTRACT TRUNCATED AT 250 WORDS)

17-Hydroxysteroid Dehydrogenases↗
PubMed1984

External quality assessment of serum hormone determinations in the Nordic countries.

Since 1979 the Nordic Clinical Chemistry Project (NORDKEM) has organized four external quality assessment surveys of serum hormone determinations in the five Nordic countries. Charcoal-stripped control sera with weighed additions of the following hormones have been used: thyrotropin, human placental lactogen, prolactin, estriol, estradiol, testosterone, cortisol, triiodothyronine, thyroxine, and, in the fourth survey, progesterone. Human serum was usually used but in the first survey the serum matrix for the protein hormones was calf serum. In three years no systematic improvement in the coefficients of variation of the results has occurred. The change from calf serum to human serum also had no major effects on the results. Percentage coefficients of bias usually varied on both sides of the true value, but at low hormone concentrations the results were almost always positively biased. It is therefore useful to know the true hormone concentrations of the control samples because all-laboratory means are relatively often biased from these. Variation produced by different methods of calculation of the radioimmunoassay results and the influence of outlying standard points on these data processing routines were studied in the third survey. It is possible that sometimes the variation produced by different methods of calculation is one of the main components of the total variation in external quality assessment of RIA. There were no major differences between the performance of computerized or manual calculation methods. The influence of different calibration standards on serum thyroxine determination was studied in the fourth survey. Of the total coefficient of variation (10.8% to 17.0%) the component of variation produced by different thyroxine calibration standards was 0.8% to 4.6%. In conclusion, standardization of the data processing methods and further standardization of assay reagents are urgently needed to give possibilities to identify more subtle differences in the analytical performance of the laboratories. External quality assessment of hormone determinations needs improvement of the quality of reference materials.

Chemistry, Clinical↗
PubMed1984

Internal quality control of hormone determinations by RIA. Detection of clinically significant analytical errors of serum thyroxine determination.

An internal quality control system by which clinically significant analytical errors can be detected with high probability was developed for serum thyroxine (T4) determination by RIA. The mean concentration of the quality control samples (C1, C2, and C3) were 40.0, 101.8, and 156.7 nmol/l, and their total standard deviations (st) 2.5, 4.1, and 7.1 nmol/l, respectively, in stable analytical performance of the T4 assay. From the clinical point of view it was accepted that the results of C1 varied from 30 to 50 nmol/l at the most. When expressed in standard deviations, the same size of error was accepted for C2 and C3. It followed that the quality control system had to detect a systematic shift of 2.43st (delta SEc) and a 2.08 times increase in random error (delta REc) in order that the quality goals could be reached. With three control samples the combination of rules, 1: 3s/CS1: (1.0s; 2.7s), which was chosen for manual quality control, detected the delta SEc with about an 80% probability and the delta REc with about a 30% probability. The probability of false rejections was less than 1%. The probability of detecting the delta SEc was considered acceptable, but to detect the delta REc with a higher probability, the within-assay variation of each run was calculated from the results of duplicate patient samples. Although the whole run was not rejected because of systematic and/or random errors, individual samples were reanalysed if the results of their duplicate determinations differed from the criteria stated.(ABSTRACT TRUNCATED AT 250 WORDS)

False Negative Reactions↗
PubMed1984

Radioimaging of the prostate and metastases of prostatic carcinoma with 99mTc-labelled prostatic acid phosphatase-specific antibodies and their Fab fragments.

A radioimmunodetection technique using 99mTc-labelled polyclonal antibodies raised in rabbits against human prostate-specific acid phosphatase was used to detect metastases of prostatic carcinoma. All the metastases observed by X-rays or bone scintigraphy in the four patients with M1-disease were revealed by the novel technique employed. In addition, in one of the patients studied, a distinct incorporation of radioactivity was also observed in the left inferior scapular region, which was not seen by conventional bone scanning, but was later confirmed by X-ray studies to be a metastatic process.

Acid Phosphatase↗
PubMed1983

Cytosol and nuclear estrogen and progestin receptors and 17 beta-hydroxysteroid dehydrogenase activity in non-diseased tissue and in benign and malignant tumors of the human ovary.

Significant but low concentrations (mean 8 fmol/mg cytosol protein) of cytosol estrogen receptors were found in 57% of non-diseased ovarian tissues, and higher concentrations (mean 211) of cytosol progestin receptors in all these tissues. An approximately similar distribution was found for the presence of nuclear female sex steroid receptors; the mean concentrations were 159 and 1149 sites/cell, for estrogen and progestin receptors, respectively. There were no major differences in these parameters between pre- and postmenopausal non-diseased ovaries. The activities of ovarian 17 beta-hydroxysteroid dehydrogenase (17-HSD) did not display correlations between circulating progesterone concentrations in pre- or postmenopausal women with non-diseased ovaries. The majority of benign epithelial tumors contained significant concentrations of cytosol estrogen receptors, and all showed cytosol progestin receptors. The concentration of estrogen receptors was identical to that seen in non-diseased ovaries (mean 9 fmol/mg cytosol protein), whereas that of progestin receptor was significantly lower (mean 95). Nuclear female sex steroid receptors were measured in all benign tumors, and their concentrations were significantly higher than in normal ovaries (440 and 3218 sites/cell for estrogen and progestin receptors, respectively). No difference in 17-HSD activities were detected between normal ovaries and benign tumors. In malignant ovarian tumors, the picture was different from that found in normal ovarian tissues and benign tumors. Cytosol estrogen receptor was found in 89% of malignant epithelial tumors, and its concentration was significantly higher (mean 64 fmol/mg cytosol protein). Cytosol progestin receptor was found in 91%, and its concentration (mean 75) was significantly lower than in normal ovarian tissue or benign ovarian tumors. Nuclear female sex steroid receptor concentrations were intermediate between those seen in non-diseased ovaries an in benign tumors. 17-HSD activity was significantly lower than in other tissue categories studied. In the small group (16) of non-epithelial ovarian carcinomas cytosol estrogen receptors were not found, whereas the results of other measurements did not display any coherent picture. Breast and endometrial carcinoma metastatic to the ovary showed receptor patterns which were typical of the primary tumors. When the different clinical stages (I-IV) of malignant epithelial ovarian tumors were compared, 17-HSD activity was significantly higher in the least advanced clinical stage (I), whereas no significant differences were found in the other parameters measured.(ABSTRACT TRUNCATED AT 400 WORDS)

17-Hydroxysteroid Dehydrogenases↗
PubMed1983

Pregnenolone and its sulfate ester in the rat brain.

Pregnenolone (P) and its sulfate ester (PS) have been characterized in the brain of adult male rats. The concentration of P (38.4 +/- 6.9 and 22.1 +/- 2.9 ng/g, mean +/- S.D., in anterior and posterior brain, respectively) exceeded that of PS in brain (15.8 +/- 3.0 and 5.7 +/- 2.1 ng/g in the same fractions) and largely those of P and PS in plasma (1.3 +/- 0.2 and 1.4 +/- 0.3 ng/g, respectively). The level of P in brain was much larger than that of dehydroepiandrosterone sulfate (DS), characterized and measured previously (Corpéchot et al.). Brain P and PS levels did not seem to depend on steroidogenic gland secretion: no meaningful difference occurred in brain 15 days after adrenalectomy plus orchiectomy, compared with sham-operated controls. It is proposed that, as that of DS (ref. 5) P and PS formation or accumulation (or both) in the rat brain depend on in situ mechanisms unrelated to the peripheral endocrine gland system.

Animals↗
PubMed1983

Nuclear androgen receptors in the epithelium and stroma of human benign prostatic hypertrophic glands.

Androgen receptors have been characterized and quantified in nuclear extracts of separated epithelium and stroma from human benign prostatic hypertrophic (BPH) glands. Tritiated dihydrotestosterone was used as the ligand and incubation was carried out at 15 degrees C for 18-20 hr before separation of bound and free ligand using dextran-coated charcoal. The results were analysed by Scatchard-type analysis. The concentration of receptor was found to be significantly (p = 0.022) greater in stromal than in epithelial nuclei: 1765 +/- 152 vs 1030 +/- 227 fmol/mg DNA (SEM, n = 6). Fourteen competitors were tested and the results indicated the presence of specific androgen receptors rather than contaminating sex-hormone-binding globulin. This was also borne out by the results of agar gel electrophoresis and sucrose gradient ultracentrifugation studies. The results are in line with current opinion that prostatic stroma is an important androgen-sensitive tissue, particularly in human BPH.

Cell Nucleus↗
PubMed1983

Comparison of megestrol acetate and clomiphene citrate as supplemental medication in postmenopausal oestrogen replacement therapy.

In a prospective clinical trial lasting one year, 35 postmenopausal women with severe climacteric symptoms were cyclically treated with conjugated oestrogens (1.25 mg daily). This oestrogen replacement therapy was randomly supplemented with 10 mg of megestrol acetate daily (18 women) or 50 mg of clomiphene citrate (17 women) for 10 days four times a year. Both treatment regimens significantly alleviated climacteric symptoms. At the end of the oestrogen-megestrol acetate treatment no endometrial proliferation or hyperplasia was seen, while at the end of the oestrogen-clomiphene citrate treatment the endometrium was proliferative or hyperplastic in two women and atrophic in the other 15. Regular uterine bleeding occurred in each woman after megestrol acetate but never after clomiphene citrate administration. Break-through bleeding during the oestrogen treatment periods appeared in the megestrol and clomiphene groups in five and eight women, respectively. There were no clinically adverse hormonal or metabolic changes during megestrol acetate or clomiphene citrate treatment periods. Our results provide further evidence that in addition to progestins postmenopausal oestrogen replacement therapy can safely be supplemented with antioestrogen and thereby avoid the bleeding which occurs regularly after progestin withdrawal.

Climacteric↗
PubMed1983

Female sex steroid receptors in gynecological malignancies: clinical correlates.

Cytosol estrogen (ERc) and progestin (PRc) receptors were measured in 135 endometrial carcinoma specimens from 127 patients, and in 84 ovarian carcinoma specimens from 84 patients before any treatment. In endometrial carcinoma, early clinical stages (I and II) were more often receptor-rich (ERc and PRc greater than or equal to 30 fmol/mg cytosol protein) than stage III-IV tumors, or metastatic and recurrent lesions. Anaplastic lesions (grade 3) had lower receptor concentrations than moderately (grade 2) and well (grade 1) differentiated stage I lesions. PRc concentrations of the stage I malignancies clearly infiltrating into the myometrium were lower than those in superficial tumors. Our follow-up (24 months or more) data of 41 patients with clinical stage I disease, and of 21 patients with clinical stage III or IV disease show that the receptor-poor tumors tend to behave more aggressively than receptor-rich malignancies in relation to patient survival. In 59 primary epithelial ovarian carcinomas, there were no significant differences in ERc and PRc concentrations in the four clinical stages. In contrast to this, the concentrations of these receptors were significantly lower in recurrent than in primary epithelial carcinomas. In anaplastic serous carcinomas, PRc was significantly lower than in differentiated tumors, and in anaplastic endometrioid carcinomas, ERc and PRc were lower than in corresponding differentiated tumors. Follow-up (24 months or more) data of 22 patients show that patients with advanced ovarian malignancy characterized by low ERc and/or PRc concentrations survive for a shorter time than the other patients.

Cytosol↗
PubMed1983

Progesterone, androstenedione, testosterone, 5 alpha-dihydrotestosterone and androsterone concentrations in specific regions of the human brain.

The concentrations of progesterone, androstenedione, testosterone, 5 alpha-dihydrotestosterone and androsterone were determined in tissue samples from the human hypothalamus, anterior pituitary, pineal, amygdala and parietal cortex, taken at autopsy from male (n = 4) and female cadavers (n = 4) of various ages. The measurements were performed using radioimmunoassays for the individual steroids after the chromatographic purification of solvent extracts of tissue samples on Lipidex-5000TM. Preliminary qualitative analyses of the chromatographic profiles of various steroids by radioimmunoassay demonstrated the presence of these steroids in various regions of the brain, but an immunoreactive peak corresponding to 17-hydroxyprogesterone was not found. The concentrations (ng/g tissue wet wt.) of all steroids measured were either very low or below the limit of detection in brain tissues taken from male and female infants. In the adult brain, there was no difference in the distribution of steroids between the various regions studied. There was no sex difference in the brain tissue steroid concentrations, with the exception of testosterone which was clearly much higher in brain tissues from men as compared to women. Although testosterone was undetectable in most samples taken from adult women. 5 alpha-dihydrotestosterone could be measured in almost all samples, which suggests that this is the most important androgen in the human brain. When brain tissue steroid levels are compared with serum concentrations, it can be postulated that a state of equilibrium exists between the fraction of serum steroids which are not bound to high-affinity binding proteins and the amount of steroids in brain tissues.

17-alpha-Hydroxyprogesterone↗
PubMed1983

Comparison of serum steroid responses to a single injection of hCG in man and rat.

The responses of peripheral serum steroids to a single injection of hCG (80 IU/kg b wt) were compared in adult male rats and humans. Before hCG, the quantitatively dominating steroids were dehydroepiandrosterone, testosterone and 17-hydroxypregnenolone in the men, and testosterone and progesterone in the rats. One hour after hCG the concentrations of testosterone and all its precursors measured except for pregnenolone were significantly elevated in the rat serum, whereas a clear rapid response was not observed in the men. Transient blockade of C21 steroid side-chain cleavage was seen in both species at about 24-36 h after hCG, which occurred at the same time as the maximum concentration of estradiol in the men. No changes in rat serum estradiol concentrations were observed. Both species showed a secondary stimulation of testosterone and androstenedione formation at around 3 days. Our findings are compatible with the concept that the main difference in the gonadotropin-stimulated steroidogenesis in man and rat is the magnitude of the rapid steroidogenic response to hCG, which is very small in man and indicates smaller supply or lesser metabolism of mitochondrial cholesterol in human testis.

17-alpha-Hydroxypregnenolone↗
PubMed1983

Steroidogenic response to a single injection of hCG in pre- and early pubertal cryptorchid boys.

The temporal response patterns of the concentrations of serum testosterone, oestradiol, 17-hydroxyprogesterone, pregnenolone, progesterone, androstenedione and 5 alpha-dihydrotestosterone to a single i.m. dose of hCG (5000 IU/1.7 m2) were investigated in prepubertal and early pubertal cryptorchid boys, and compared with the response patterns obtained earlier in adult men. The rapid response (at approximately 2-4 h) of serum testosterone was lacking in all boys, whereas the slow response at 2-5 days was constant. The relative response (the maximum stimulated concentration vs. the basal level) of serum testosterone was 70-fold in prepubertal boys and 6-fold at early puberty, compared with 2.4-fold in adult men. Serum oestradiol and 17-hydroxyprogesterone concentrations did not increase in the prepubertal boys, but did increase at early puberty, revealing a pattern similar to that observed in adult men. Hence, the prepubertal endocrine testis appears to be very responsive to hCG stimulation, and this responsiveness is rapidly lost with advancing puberty. The absolute increases, however, were smallest in prepubertal boys, perhaps reflecting the small potential Leydig cell mass. The responses of serum oestradiol and 17-hydroxyprogesterone to hCG appeared later during the boys' development than the response of serum testosterone. The relative testosterone response was maximal in the absence of an oestradiol response. It is suggested that testicular oestradiol production in response to LH/hCG appears in the course of puberty and results in intratesticular short-loop feed-back inhibition of androgen production. This is reflected by the appearance of a 17-hydroxyprogesterone response and by a decrease in relative testosterone response.

17-alpha-Hydroxyprogesterone↗
PubMed1983

Measurement of sex hormone binding globulin in human amniotic fluid: its relationship to protein and testosterone concentrations, and fetal sex.

Sex hormone binding globulin (SHBG) has been identified and quantified in human amniotic fluid. Identification was based on its electrophoretic mobility on polyacrylamide gels and its steroid binding characteristics, which were identical to those attributed to SHBG in pregnancy serum. Amniotic fluid SHBG binding capacity was measured by competitive saturation analysis using [3H]-5 alpha-dihydrotestosterone as the labelled ligand, after removal of endogenous steroids with dextran-coated charcoal. Similar amniotic fluid SHBG binding capacities were found in samples taken during early (13-20 weeks, 8.5 +/- 5.1 (SD) nmol/l, n = 10) and late (36-37 weeks, 8.7 +/- 3.0 nmol/l, n = 28) pregnancy. In comparison with pregnancy serum SHBG levels (390 +/- 140 nmol/l, n = 5), amniotic fluid SHBG was not enriched in relation to the relative concentrations of total proteins, albumin or transferrin. Amniotic fluid is therefore not a better source for the purification of SHBG than pregnancy serum. There were no differences in amniotic fluid SHBG levels with respect to fetal sex, but positive correlations were observed between SHBG binding capacities and testosterone concentrations in amniotic fluid from both male (r = 0.68, P less than 0.001) and female (r = 0.53, P less than 0.05) fetuses. It is suggested that SHBG may sequester free testosterone in amniotic fluid, and that measurements of SHBG in amniotic fluid may help to more accurately identify fetal sex in cases where borderline amniotic fluid testosterone concentrations are found.

Amniotic Fluid↗
PubMed1983

Male pseudohermaphroditism due to deficiency of testicular 17-ketosteroid reductase.

A 12.9 year-old girl, genotypically 46, XY, and considered to have a testicular feminization syndrome, developed signs of virilization and gynaecomastia. Very high androstenedione concentrations (10-fold the mean of the reference interval in boys) in relation to low normal testosterone in peripheral serum indicated a 17-ketosteroid reductase deficiency. In addition to androstenedione, the basal peripheral levels of 17-hydroxyprogesterone and estrone were increased, being 5- and 3-fold the mean of the reference interval, respectively, whereas pregnenolone, progesterone, dehydroepiandrosterone, 5 alpha-dihydrotestosterone and estradiol concentrations were within pubertal stage-appropriate reference intervals. The total spermatic vein serum steroid concentrations were about 5-fold the mean in old men, and androstenedione, estrone and dehydroepiandrosterone were particularly elevated, whereas estradiol was normal and testosterone subnormal by a factor of 1/8. In the testis tissue, the concentration of androstenedione was extremely high, whereas that of testosterone tended to be relatively low. Our patient was obviously producing testicular steroids at her maximal rate, because no response to hCG administration was observed. This state was associated with a high-normal circulating LH concentration. The concentration of testicular LH/hCG receptors was only one-fifth of that seen in old men, which may have resulted from receptor down-regulation associated with a high degree of stimulation.

17-Hydroxysteroid Dehydrogenases↗
PubMed1983

Early menarche, a risk factor for breast cancer, indicates early onset of ovulatory cycles.

The associations between age at menarche and the hormonal patterns of adolescent menstrual cycles were investigated to obtain information as to why early menarche is an important risk factor for breast cancer. An initial group of 200 schoolgirls, 7-17 yr old, was investigated longitudinally 3 times at 1.5-yr intervals. A serum progesterone concentration in the latter part of the cycle exceeding 6.4 nmol/liter (2.0 ng/ml) was considered to signify an ovulatory cycle, and a concentration less than 1.6 nmol/liter (0.5 ng/ml) an anovulatory cycle. The frequency of ovulation depended significantly on both the time since menarche and the age at menarche (P less than 0.001 for both variables). Early menarche was associated with early onset of ovulatory cycles. The times from menarche until 50% of the cycles were ovulatory were about 1, 3, and 4.5 yr when the ages at menarche were less than 12.0, 12.0-12.9, and more than or equal to 13.0 yr, respectively. Girls with a menarcheal age below 12.0 yr had higher serum estradiol but lower testosterone and dehydroepiandrosterone concentrations than subjects with later menarche. The estradiol to dehydroepiandrosterone ratio was already higher before menarche in subjects who displayed early menarche during follow-up. These findings show that the increase in adrenal androgen secretion was mainly related to chronological age and was not affected by the time of menarche. The demonstration of early ovulation after early menarche is in conflict with the estrogen-window hypothesis suggesting a longer duration of anovulatory cycles to explain the increased risk of breast cancer after early menarche. Other theories should therefore be considered, among them the following: 1) high serum progesterone concentration in association with normal or high serum estradiol at puberty increases the risk, 2) only the early and relatively high estrogen concentrations are important, or 3) the estrogen to androgen ratio is the critical factor, with androgens having a protective effect.

Adolescent↗