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Biomedical subjects

D Apter

Publications and source records attributed to D Apter.

At least 37 records · Page 2Linked to original sources
PubMed1993

Development of children and adolescents: physiological, pathophysiological, and therapeutic aspects.

Luteinizing hormone (LH) secretion is pulsatile with nocturnal augmentation even in prepubertal children, though at very low concentrations. With puberty wake-time, LH concentration increases 100-fold. Rising estradiol levels transiently increase growth hormone (GH) concentrations, which in turn leads to increases in insulin-like growth factor (IGF)-I, insulin resistance, and physiological hyper-insulinemia. In addition to estrogens, GH-IGF are important in accretion of bone mineral density (BMD) in puberty, and hypofunction may cause permanent low bone density. Growth hormone treatment of girls with Turner syndrome increases final height.

Adolescent↗
PubMed1990

Pharmacokinetics of 3-keto-desogestrel and ethinylestradiol released from different types of contraceptive vaginal rings.

Pharmacokinetics of 3-keto-desogestrel and ethinylestradiol released from contraceptive vaginal rings (CVRs) with different release rates (75/15, 100/15 and 150/15 micrograms 3-keto-desogestrel/ethinylestradiol daily) were investigated in two studies in young healthy female volunteers. As reference, an oral preparation containing 150 micrograms desogestrel and 30 micrograms ethinylestradiol (MarvelonR tablets) was also administered to the volunteers. To assess the disposition parameters of 3-keto-desogestrel and ethinylestradiol, some of the volunteers were additionally given an i.v. preparation containing 150 micrograms 3-keto-desogestrel and 30 micrograms ethinylestradiol. Serum levels obtained with CVRs showed an initial increase during the first three days, followed by a plateau decreasing only slightly during the remainder of the treatment period. Mean plateau levels (+/- s.d.) of 3-keto-desogestrel were 2.3 +/- 0.9, 2.8 +/- 1.1 and 3.8 +/- 1.1 pmol/ml for CVR 75/15, 100/15 and 150/15, respectively. Mean plateau levels of ethinylestradiol were 184 +/- 75, 262 +/- 102 and 233 +/- 102 pmol/l, respectively. The in vivo release rates of 3-keto-desogestrel and ethinylestradiol from the CVRs were in good agreement with the in vitro release rates. For both steroids the bioavailability from the CVRs was approximately 1.2 times higher than that from the tablets. The 3-keto-desogestrel serum levels were found directly proportional to the release rates within the range studied (75-150 micrograms/day). For ethinylesteradiol the intra-individual variation in steady-state levels was too large to draw pertinent conclusions.

Administration, Oral↗
PubMed1990

Clinical performance and endocrine profiles of contraceptive vaginal rings releasing 3-keto-desogestrel and ethinylestradiol.

The clinical performance and endocrine profiles of contraceptive vaginal rings (CVR) with an in vitro daily release rate of 15 micrograms of ethinylestradiol combined with 75, 100 or 150 micrograms 3-keto-desogestrel were evaluated. Two studies were performed; one with 11 volunteers, consisting of a control cycle, a cycle with an oral preparation (Marvelon), followed by two CVR treatment cycles, and a second study with 12 volunteers, having the same design but one CVR treatment cycle. A dose-response relationship was seen in the endocrine and clinical performance of the CVR. With CVR 75/15, ovulation occurred in two subjects, and increases in serum estradiol concentrations were seen in two additional subjects. With CVR 100/15, slight estradiol increases were seen in four subjects, but progesterone remained low. With CVR 150/15, both estradiol and progesterone serum concentrations remained low. With CVR 75/15 extra bleeding was common, but with CVR 150/15 this did not occur. No major side effects occurred, and no abnormal Papanicolaou smears or histological findings of the endometrium were found. All volunteers completed all cycles, and the three-week CVR use was generally well accepted. In conclusion, the release rate of CVR 75/15 was insufficient. A vaginal ring with a daily release rate between 100 and 150 micrograms of 3-keto-desogestrel in combination with 15 micrograms of ethinylestradiol seems suitable for contraceptive purposes, and will be further tested in larger clinical studies.

Adult↗
PubMed1990

Serum CA 125 levels during the menstrual cycle.

Serum concentrations of CA 125 were measured in different phases of the menstrual cycle in 16 women with ovulatory and 12 women with anovulatory cycles. CA 125 levels were significantly elevated during menstruation in both groups. In women with anovulatory cycles, but not in those with ovulatory cycles, CA 125 levels were already increased in the premenstrual phase. A negative correlation was found between serum CA 125 and progesterone concentrations in the premenstrual phase of the cycle. We suggest that premenstrual elevation of serum CA 125 in women with anovulatory cycles is related to premature endometrial vascular changes which are the result of the low serum progesterone concentration leading to insufficient endometrial control. Thus the effect of progesterone seems to be indirect rather than a direct effect on CA 125 synthesis. When the CA 125 assay is used for diagnosis of cancer, sampling should not be done immediately before or during menstruation because the physiological elevation of the CA 125 levels may give false positive results.

Adolescent↗
PubMed1990

Endocrine determinants of fertility: serum androgen concentrations during follow-up of adolescents into the third decade of life.

We have completed a 13-yr longitudinal study of endocrine features in females originally aged 7-17 yr and report now factors related to fertility in these women, mainly serum testosterone (T) and androstenedione (A) concentrations in relation to becoming pregnant. Longitudinal regression analysis, corrected for the effect of age, showed that current serum T and A concentrations are correlated with those measured 12 yr earlier (T: r = 0.47, P less than 0.01; A: r = 0.57, P less than 0.001). Age-adjusted serum T and A concentrations before any pregnancies were higher in women who subsequently had no pregnancies than in those who had been pregnant (T: never pregnant, mean +/- SEM, 1.10 +/- 0.06 nmol/L, pregnant 0.81 +/- 0.07 nmol/L, P = 0.004; A: never pregnant 4.00 +/- 0.28 nmol/L, pregnant 2.98 +/- 0.33 nmol/L, P = 0.03). Serum androgen concentrations were not related to variables reflecting sexual behavior and the use of oral contraception. The data therefore show that adolescent serum androgen concentrations are preserved into adulthood and are reflected in fertility patterns during the third decade of life. Higher serum androgen concentrations are associated with lower fertility. Together with our previous findings, these data demonstrate that endocrine characteristics formed during puberty seem to persist at least until 30 yr of age.

Adolescent↗
PubMed1989

Some endocrine characteristics of early menarche, a risk factor for breast cancer, are preserved into adulthood.

Early menarche is a risk factor for breast cancer. In a longitudinal manner, we have investigated the endocrine features of girls with early menarche. This study extends our investigations to the third decade of life in a cohort of girls followed up for 13 years. The group studied comprised 44 women, 20-31 years of age. Eleven women had had their menarche before 12.0 years, 14 women at 12.0-12.9 years and 19 women at 13.0 years or more. The women who had had early menarche had higher serum oestradiol concentrations during the follicular phase of the menstrual cycle than the women who had had their menarche later. The serum oestradiol concentrations increased rapidly at the beginning of cycle in these "early menarche" women. If there is a threshold which serum oestradiol concentrations must exceed to increase the risk of breast cancer, then these women have more days at risk than other women. In addition, the serum SHBG (sex-hormone-binding globulin) concentration was about 30% lower in the follicular-phase specimens of the women who had had their menarche before 12.0 years compared with those who had had their menarche at 13.0 years. Our data therefore indicate that women with early menarche are subject to a high degree of oestrogen stimulation at least until approximately 30 years of age. Our findings may have important consequences for the design of intervention programs for breast cancer prevention.

Age Factors↗
PubMed1989

Pulsatility of serum-luteinizing hormone during hyperstimulation with clomiphene citrate and human menopausal gonadotropin for in vitro fertilization.

The pulsatile pattern of gonadotropin secretion regulates follicular growth and corpus luteum function in normal cycles, but the role of endogenous gonadotropin pulses in hyperstimulated cycles is unclear. We studied pulsatility of serum-luteinizing hormone (LH) in the late follicular and midluteal phases in four women after hyperstimulation with clomiphene citrate, human menopausal gonadotropin, and human chorionic gonadotropin, and in five women with normal untreated cycles. In the late follicular phase, the number, interval, amplitude, and area of LH pulses did not show significant differences between hyperstimulated and control cycles. In the midluteal phase, the long-lasting (greater than 90 minutes) LH pulses typical for the normal luteal phase, were not found after hyperstimulation. As the length of the luteal phase in these cases was normal, the significance of this finding remained obscure.

Clomiphene↗
PubMed1989

Endogenous steroids in the pathophysiology of breast cancer.

The search for major endocrine abnormalities as causes for breast cancer has not been successful, whether it has been directed at patients with this disease or at different groups or populations at risk. An early-onset, long-lasting ovulatory cycle function seems to be prevalent in different risk categories for breast cancer. Women with early menarche, compared with those with late menarche, are additionally characterized as having higher circulating estradiol and lower sex-hormone-binding globulin concentrations. A number of additional findings point to estradiol as a central agent in the development of breast cancer, and cyclic progesterone secretion does not seem to have a clearly opposing action.

Androgens↗
PubMed1989

Serum luteinizing hormone concentrations increase 100-fold in females from 7 years to adulthood, as measured by time-resolved immunofluorometric assay.

The increases in serum immunoreactive (RIA) LH and FSH concentrations during puberty are small and of limited value in the evaluation of pubertal development. We, therefore, used highly sensitive time-resolved immunofluorometric assays to evaluate the changes in LH and FSH during female puberty. The sensitivity of the LH assay was 0.02 IU/L, and that of the FSH assay was 0.01 IU/L. Fifty normal premenarcheal girls, 7-12 yr old, 15 postmenarcheal girls, 16 to 17 yr old, and 15 adult women, 24-29 yr old, were studied. In postmenarcheal women, the blood samples were taken on cycle days 4-7. Serum estradiol concentrations were measured by RIA, and pubertal stages were graded. Serum LH levels in prepubertal girls were very low; the mean concentration was 0.05 IU/L. All girls less than 10 yr of age had serum LH concentrations below 0.2 IU/L, while FSH levels varied from 0.3-2.0 IU/L. The earliest significant changes in serum LH, FSH, and estradiol levels took place simultaneously at 9-10 yr of age. The increase in serum FSH was gradual, but the increase in serum LH was sudden and very steep, coinciding with the increase in serum estradiol and the onset of physical puberty. The increase in the mean LH concentrations between the 7-yr-old and the adult group was 116-fold, that for estradiol was 12-fold, and that for FSH was 6.7-fold. These results suggest that the increase in serum LH is important at the onset of puberty, and LH concentrations are a sensitive indicator of pubertal development.

Adolescent↗
PubMed1987

Plasma beta-endorphin, beta-lipotropin and corticotropin in polycystic ovarian disease.

In 9 women with polycystic ovarian disease (PCOD) and in 11 control subjects at the follicular phase of the normal cycle, blood samples were collected at 15-min intervals during a 2 h period of bed rest for the assay of beta-endorphin, beta-lipotropin, corticotropin, cortisol and prolactin. During the study period, the plasma levels of these hormones decreased more significantly in the PCOD than in the control group, suggesting that the PCOD patients had a more significant stress response to the puncture of the vein than the control subjects. The second hour of the study period was considered to represent resting levels of hormones. The mean resting levels (+/- S.E.) of the hormones between the PCOD and control groups, respectively, were as follows: beta-E, 2.0 +/- 0.4 vs. 1.1 +/- 0.1 pmol/l, p less than 0.05; beta-LPH, 3.4 +/- 0.6 vs. 2.1 +/- 0.5 pmol/l, N.S.; corticotropin, 2.0 +/- 0.3 vs. 1.1 +/- 0.5 pmol/l, p less than 0.05; cortisol, 176 +/- 24 vs. 128 +/- 16, N.S.; and prolactin; 3.9 +/- 0.6 vs. 5.6 +/- 1.2 ng/ml, N.S. These results confirm the previous findings on increased circulating levels of beta-E in PCOD. A concomitant increase of the plasma level of corticotropin suggests that the basal secretion of both beta-E and corticotropin from the anterior pituitary gland is increased in women with PCOD.

Adrenocorticotropic Hormone↗
PubMed1987

Follicular growth in relation to serum hormonal patterns in adolescent compared with adult menstrual cycles.

The purpose of this study was to clarify the endocrine regulation of the adolescent menstrual cycle, especially the relationships between ovarian follicular development, luteal phase progesterone secretion, and function of the hypothalamic-pituitary unit. One menstrual cycle of each of 17 women who were 15 and 16 years of age and 12 women who were 25 to 35 years of age was characterized by ultrasonography and hormone measurements. In both groups there was a close correlation between follicle size and serum estradiol concentrations. In the adolescents, follicle development was slower, and an eventual ovulation took place from a smaller follicle than in the older group. The immediate preovulatory follicle size correlated with the maximal serum progesterone concentration during the luteal phase. Late follicular development in adolescents may be related to the slow increase of serum follicle-stimulating hormone concentrations early in the cycle.

Adolescent↗
PubMed1986

Plasma immunoreactive beta-endorphin in exercise-associated amenorrhea.

During 2 hours of bed rest, plasma samples were taken at 15-minute intervals from nine women with exercise-associated amenorrhea and in 11 control women in the follicular phase of a normal menstrual cycle. Concentrations of immunoreactive beta-endorphin, cortisol, prolactin, luteinizing hormone, follicle-stimulating hormone, and estradiol were determined. During the first hour, cortisol levels decreased significantly in both groups and reached a plateau during the second hour, which period was considered to represent resting levels of the hormones. The amenorrhea group showed higher mean (+/- SE) resting levels of immunoreactive beta-endorphin (11.0 +/- 0.8 versus 8.3 +/- 0.6 pg/ml, p less than 0.05) and cortisol (274 +/- 35 versus 134 +/- 14 nmol/L, p less than 0.001) and lower mean resting levels of prolactin (2.4 +/- 0.3 versus 5.7 +/- 1.1 ng/ml, p less than 0.01), luteinizing hormone (4.0 +/- 0.7 versus 10.5 +/- 1.8 IU/L, p less than 0.01), and estradiol (0.09 +/- 0.01 versus 0.19 +/- 0.07 nmol/L, p less than 0.05) than the control group. These results suggest that exercise increases basal endorphin secretion in amenorrheic women and support the theory that increased opioid activity may be involved in the pathophysiology of exercise-associated amenorrhea.

Adolescent↗
PubMed1986

Serum levels of placental protein 14 reflect ovulation in nonconceptional menstrual cycles.

Placental protein 14 (PP14), originally isolated from the human placenta and its adjacent membranes, was detected in the serum of nonpregnant women. The levels were measured by radioimmunoassay in 218 serum samples from 19 women throughout the menstrual cycle. In 13 women with a normal ovulatory cycle, the levels showed consistent variation. They were highest (up to 172 ng/ml) in the late secretory phase and remained high for the first days of the next cycle. Low concentrations were found from the midproliferative to the early luteal phase of the cycle. No similar variation was seen in anovulatory cycles of six other women. Compared with ovulatory cycles, anovulatory cycles exhibited lower PP14 levels in the latter part of the cycle (P less than 0.001) and in the beginning of the next cycle (P less than 0.01). In ovulatory cycles, the sustained elevation of serum PP14 concentration over the following period may be explained by the fairly long half-life (42 hours) of PP14 in serum: once the level has increased, it declines slowly. These results suggest that PP14 measurement may become a novel means to distinguish between ovulatory and anovulatory cycles even after the onset of the next period.

Adolescent↗
PubMed1985

Premenarcheal endocrine changes in relation to age at menarche.

Pubertal development preceding menarche in normal girls having menarche at a relatively early age (11.3-12.9 years) was compared with the development of girls having menarche later (13.0-14.9 years of age). Eighty-four premenarcheal girls, 7.3-14.3 years old, were examined and their age at menarche was recorded during this longitudinal study. Girls with early menarche had a larger increase in serum oestradiol at about 10 years of chronological age, and after that age the concentrations remained higher than in girls having later menarche. Serum FSH concentrations tended to be slightly higher at the onset of puberty in the former group, even before differences in serum oestradiol concentrations were observed. Pubertal development was faster in girls having early menarche, as indicated by the significantly shorter time from both breast and public hair stage 2 to menarche. This rapid sequence can be related to the higher oestradiol levels. A dissociation between gonadarche and adrenarche was evident. The oestradiol/dehydroepiandrosterone (DHEA) ratio was higher in girls developing early menarche. Around the onset of puberty (9.0-11.5 years of age) there was a complete lack of correlation between serum DHEA concentrations and age at menarche, whereas serum FSH and oestradiol concentrations displayed strong correlations with age at menarche. The present data support the view that girls with early menarche have a more profound decrease in the sensitivity of the hypothalamic-pituitary unit to the negative feed-back of circulating steroids.

Adolescent↗
PubMed1985

Kinetics of the steroidogenic response to single versus repeated doses of human chorionic gonadotropin in boys in prepuberty and early puberty.

There is accumulating evidence that in adult men excessive amounts of gonadotropins induce testicular desensitization to further gonadotropin stimulus. We evaluated the effects of endogenous gonadotropins and of repeated doses of exogenous human chorionic gonadotropin (hCG) on steroidogenesis by studying prepubertal and pubertal boys. The boys received either two intramuscular injections of hCG 4 days apart (protocol I) or four injections at 3- to 4-day-intervals (protocol II). In protocol I, serum testosterone, 17 alpha-hydroxyprogesterone, and estradiol were measured basally and for 6 days after the second injection, and in protocol II, before each injection and 4 days after the last injection. In the prepubertal-boys, serum testosterone increased from very low basal levels to 10.3 (protocol I) and 8.3 nmol/liter (protocol II). In protocol I the increase after the first injection was 64-fold and in protocol II there was an increase after each injection to a final level 144-fold of the basal. No significant changes were seen in the estradiol levels. In the pubertal boys at genital stage G2, the serum testosterone levels increased after the first two injections, but at genital stage G3, the levels increased only after the first injection. Maximal testosterone increases were 27- and 8-fold, respectively. In pubertal boys estradiol levels increased progressively throughout the stimulation. The major testosterone response ws seen after the first dose of hCG and repeated doses, at least in the pubertal boys, increased estradiol but not testosterone levels, thus causing an estrogen-mediated 17,20-lyase block. We therefore suggest that a single-dose hCG test deserves further evaluation for diagnostic use.

17-alpha-Hydroxyprogesterone↗
PubMed1984

Endocrine characteristics of adolescent menstrual cycles: impact of early menarche.

An initial group of 200 girls, 7-17 years old, was investigated longitudinally 4 times at 1.5-, 1.5- and 5-year intervals. The present study gives information of the impact of early menarche, a risk factor for breast cancer, on some physical and endocrine characteristics in these subjects. The frequency of ovulation depended significantly on both the time since menarche and the age at menarche. Early menarche was associated with early onset of ovulatory cycles. Even in early puberty, before menarche, the subjects who displayed early menarche during follow-up had higher serum FSH and estradiol concentrations than the girls whose menarche took place after the age of 13.0 years. Adrenal androgen secretion (dehydroepiandrosterone) was not influenced by age at menarche but it increased, as expected, on the basis of chronological age. The group with early menarche was characterized by high circulating estradiol concentrations also after menarche, even in the oldest subjects so far studied, 17-25 years of chronological age. At these ages, the differences in the frequencies of ovulatory cycles were disappearing between the groups formed on the basis of age at menarche. The present findings in pre- and postmenarcheal subjects suggest that the increased risk of breast cancer associated with early menarche is created over several years of exposure to high-level estrogen stimulus.

Adolescent↗