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Biomedical subjects

D Apter

Publications and source records attributed to D Apter.

At least 19 recordsLinked to original sources
PubMed2001

Efficacy, tolerability and acceptability of a novel contraceptive vaginal ring releasing etonogestrel and ethinyl oestradiol.

A novel contraceptive vaginal ring releasing etonogestrel 120 microg and ethinyl oestradiol 15 microg daily over a period of 3 weeks was tested. Each ring was used for one cycle, comprising 3 weeks of ring use followed by a 1 week ring-free period. This 1 year, multicentre study assessed the contraceptive efficacy, cycle control, tolerability and acceptability of the contraceptive. Altogether, 1145 women were exposed to the vaginal ring for 12,109 cycles (928 woman-years). Six pregnancies occurred during treatment, giving a Pearl Index of 0.65 (95% confidence interval 0.24--1.41). Cycle control was very good, since irregular bleeding was rare (2.6--6.4% of evaluable cycles) and withdrawal bleeding (mean duration 4.7--5.3 days) occurred in 97.9--99.4% of evaluable cycles. Compliance to the prescribed regimen was high with criteria being fulfilled in 90.8% of cycles. The ring was well tolerated. The majority of women considered this new contraceptive method easy to use, and it offers an effective, convenient, well-accepted and novel method for hormonal contraception.

Cervix Uteri↗
PubMed2000

The decrease in luteinizing hormone secretion in response to weight reduction is inversely related to the severity of insulin resistance in overweight women.

Controversial effects of weight reduction on gonadotropin secretion in obesity have been reported. As a result of pulsatility, single serum samples or frequent sampling studies are somewhat limited with regard to monitoring LH and FSH concentrations. We studied follicular phase nocturnal urinary (nu) LH and FSH secretion and glucose metabolism (150-min euglycemic hyperinsulinemic clamp) during 1 menstrual cycle/30-day period before and after weight reduction in 10 severely overweight infertility patients (age, 29 +/- 3.1 yr; body mass index, 37.1 +/- 3.3 kg/m2; +/-SEM). A 6-week very low calorie diet was followed by a 4-week normocaloric period. The urinary LH and FSH results reported represent samples taken 12 to 2 days before the LH surge, or 10 consecutive samples in the case of amenorrhea. We observed a decrease of 8% (P < 0.001) in percent body fat mass and a 5% (P < 0.005) reduction in waist to hip ratio. Mean nu-LH decreased by 45% [6.06 +/- 1.05 (+/-SEM) to 3.22 +/- 0.71 IU/L], whereas mean nu-FSH remained unchanged. Insulin-stimulated glucose uptake increased by 41% (P < 0.01), which was accounted for by a significant increase in nonoxidative glucose disposal (P = 0.003). Serum sex hormone-binding globulin concentrations increased by 39% (P < 0.01), and insulin-like growth factor (IGF)-binding protein-1 (IGFBP-1) levels increased by 46% (P < 0.05). Fasting serum insulin concentrations decreased by 38%, those of leptin by 37%, those of androstenedione by 32%, those of testosterone by 20% (all P < 0.01), and those of dehydroepiandrosterone sulfate by 13% (P < 0.05). The percent change in nu-LH correlated negatively with glucose uptake (r = -0.76; P < 0.01) and the increase in serum sex hormone-binding globulin (r = -0.85; P < 0.005) and positively with the percent change in waist to hip ratio (r = 0.79; P < 0.01). The absolute nu-LH levels after weight reduction correlated significantly with fasting insulin concentrations (r = 0.88; P < 0.001) and negatively with glucose uptake (r = -0.67; P < 0.05). No significant relationships were found between absolute levels or changes in nu-LH concentrations and leptin, IGF-I, IGFBP-3, or IGFBP-1 concentrations. Our findings suggest that weight reduction with a very low calorie diet results in a decrease in nu-LH concentrations, a reduction in the LH/FSH ratio, and FSH predominance favoring folliculogenesis. The decrease in LH concentrations is inversely related to the severity of insulin resistance. It is possible that the decrease in LH secretion with weight reduction is more dependent on the absolute levels of insulin sensitivity than on the degree of general adiposity.

Adult↗
PubMed1999

Serum and follicular fluid leptin during in vitro fertilization: relationship among leptin increase, body fat mass, and reduced ovarian response.

The satiety factor leptin is expressed in several reproductive tissues, but its role in the control of reproductive physiology is not well understood. We studied leptin concentrations in the sera and follicle fluids of 52 women [body fat mass percentage (BFM%) range, 19.6-38.8%] undergoing pituitary down-regulation and ovarian hyperstimulation for in vitro fertilization (IVF) treatment. Fasting serum samples were collected 1) at maximal suppression before the initiation of gonadotropin treatment, 2) at maximal ovarian hyperstimulation, 3) at the time of oocyte retrieval, and 4) 16 days later when all subjects were under exogenous luteal support using 600 mg progesterone daily. Follicular fluid (FF) was obtained at oocyte retrieval from two representative preovulatory follicles in both ovaries. During ovarian hyperstimulation there was a significant 60% increase in serum leptin concentrations from 10.9 +/- 1.1 (SEM) to 15.7 +/- 1.5 ng/mL (P < 0.01) between suppression and maximal hyperstimulation, demonstrating that the ovarian functional state can affect serum leptin concentrations. A serum leptin increase of 22-198% during ovarian hyperstimulation was evident in 43 subjects, whereas in 9, leptin concentrations remained unchanged. A positive correlation between leptin change and BFM% (r = 0.55; P < 0.0005) was observed in the 43 leptin responders. The follicular fluid leptin level was similar to that in serum. In separate linear regression analysis, BFM% contributed to 59-64%, body mass index to 46-56%, and weight to 46-55% (all P < 0.001) of the variability in leptin concentrations at the 4 time points. The 20-fold increase in serum estradiol concentrations during IVF was not significantly correlated with changes in leptin concentrations. On the contrary, the relative serum leptin increase was negatively associated with the ovarian response to hyperstimulation, as revealed by the numbers of follicles (b = -0.28; r2 = 8.1%; P < 0.05) and oocytes retrieved (b = -0.39; r2 = 15.2%; P < 0.01). This relationship was further reflected in a positive correlation between the percent increases in leptin and FSH concentrations (r = 0.39; P < 0.01). The significant relationship of high leptin and reduced ovarian response was also maintained when the cumulative dose of FSH was used as a covariable. Reduced ovarian response was not a function of body mass index, BFM%, basal leptin levels, or insulin concentrations. Fasting serum insulin concentrations remained unchanged in response to IVF, but were positively correlated to serum leptin concentrations at all four time points. Our data suggest that leptin production may be influenced by the ovarian functional state. During IVF a high relative leptin increase is associated with adiposity and a reduced ovarian response. These observations support the possibility that high leptin concentrations might reduce ovarian responsiveness to gonadotropins. Hence, leptin might explain in part why obese individuals require higher amounts of gonadotropins than lean subjects to achieve ovarian hyperstimulation.

Adipose Tissue↗
PubMed1998

Possible mechanisms mediating an association between physical activity and breast cancer.

The epidemiologic, methodologic, and biologic evidence that physical activity may be related inversely to breast cancer risk was the focus of a recent workshop. This article presents the workshop summary on biologic mechanisms that may mediate this association between physical activity and breast cancer. There is some evidence that physical activity may reduce breast cancer risk, although the exact biologic pathways have not been determined. Among the potential mechanisms discussed at the workshop were reductions in endogenous steroid exposure, alterations in menstrual cycle patterns, delay of age at menarche, increased energy expenditure and reduction in body weight, changes in insulin-like and other growth factors, and enhancement of natural immune mechanisms. Although physical activity may prove to be a modifiable risk factor for breast cancer, further mechanistically oriented research is necessary to both verify whether this is the case and to clarify the details of this association so that public health recommendations can be developed.

Breast Neoplasms↗
PubMed1998

How possible is the prevention of polycystic ovary syndrome development in adolescent patients with early onset of hyperandrogenism.

The polycystic ovary syndrome has a pubertal onset, with menstrual cycle irregularities and infertility in adulthood, as well as general health hazards such as increased risk for diabetes mellitus and myocardial infarction. Thus, prevention would be important. But as specific etiological factors are not known, nor is specific intervention. In order to use long-term intervention programs in children and adolescents, particularly rigid criteria must be used regarding proven safety and efficacy. In obese subjects, weight loss is very important, having beneficial effects on most aspects of the syndrome, such as subjective symptoms, infertility, hyperinsulinemia and related metabolic aberrations, and long-term health risks. Well controlled, long-term follow-up studies are needed on the role of prepubertal hyperandrogenism, hyperinsulinemia, gonadotropins, and ovarian morphological aspects in the development of PCOS, and possibilities of prevention.

Adolescent↗
PubMed1997

Development of the hypothalamic-pituitary-ovarian axis.

The onset of puberty is a centrally driven process, the detailed mechanisms of which are not known. It is translated into an increased activity of the hypothalamic GnRH pulse generator. This in turn is seen as increased pituitary pulsatile secretion of LH and FSH. LH pulses are observed even in midchildhood, particularly after the onset of sleep. Onset of puberty is associated with a greater increase in LH pulse amplitude than frequency and a much greater increase in LH and FSH. A progressive increase in daytime pulsatility occurs, with a gradual reduction of sleep-entrained amplification. Prepubertal FSH concentrations are relatively high in girls, and continous ovarian follicular growth and atresia take place, with estradiol concentrations being higher than in boys. Only after the steep early pubertal increase in LH, ovarian steroidogenesis is activated, with increases in androgen and estrogen secretion. Under further FSH stimulation, follicular growth and maturation proceed. The first menstrual cycles are mostly anovulatory for 1 to 2 years. Luteal phase insufficiency is common the first five years after menarche.

Female↗
PubMed1997

First-void urine testing for Chlamydia trachomatis by polymerase chain reaction in asymptomatic women.

BACKGROUND: Because Chlamydia trachomatis infections are usually asymptomatic or minimally symptomatic, diagnosis is often delayed. GOAL: To perform a comparative study of first-void urine (FVU) polymerase chain reaction (PCR) testing and endocervical swab antigen testing in the diagnosis of C. trachomatis infection among asymptomatic women. STUDY DESIGN: The study population consisted of 1,090 unselected women attending a family planning clinic or a university student health clinic. Calculations of test performances were based on an expanded reference standard including enzyme immunoassay (EIA) or PCR tests confirmed by direct fluorescence antibody (DFA) test or major outer membrane protein PCR test, respectively. RESULTS: The overall prevalence of C. trachomatis infection was 5.6%. After resolution of discrepant specimens, FVU PCR detected 85% (52/61) and endocervical swab EIA/DFA 90% (55/61) of confirmed positive cases. CONCLUSIONS: These results indicate that the FVU PCR test is an accurate, noninvasive screening method and can replace endocervical swab EIA in the detection of C. trachomatis infection in low-prevalence populations.

Chlamydia Infections↗
PubMed1996

Circulating levels of follistatin from puberty to menopause.

OBJECTIVE: To determine the changes in circulating levels of follistatin, a binding protein for activin and inhibin, through the reproductive life cycle in women. DESIGN: An open, prospective descriptive study. SETTING: An academic endocrine research unit. PATIENTS: Prepubertal (n = 10), midpubertal (n = 7), and postpubertal (n = 25) (early adolescent) girls, normal cycling adult women (n = 8), postmenopausal women (n = 17), and men (n = 13) were studied. INTERVENTIONS: Normal cycling women were given Nal-Glu GnRH antagonist for 3 days in the follicular phase of the cycle. MAIN OUTCOME MEASURE: Serum concentrations of follistatin determined in a heterologous RIA. RESULTS: Mean follistatin levels did not change during puberty but were higher in adult and postmenopausal women. Levels of immunoreactive follistatin in men were lower than levels found in normal cycling women and postmenopausal women. Daily immunoreactive follistatin levels during the menstrual cycle remained constant and did not change significantly after ovarian suppression with GnRH antagonist. CONCLUSION: Because dynamic changes of serum immunoreactive follistatin do not occur during ovarian activation (puberty), suppression, and age-related ovarian failure, the increase in immunoreactive follistatin levels in adult and postmenopausal women may implicate sources of follistatin other than the ovary.

Adolescent↗
PubMed1996

Hormonal events during female puberty in relation to breast cancer risk.

The time from puberty to the first pregnancy is particularly important for breast cancer risk, with early menarche increasing the risk of breast cancer. The onset of puberty is elicited by an increase in gonadotropin secretion, that can be modified by metabolic factors. Girls going to have an early menarche, have an earlier and greater increase of follicle stimulating hormone and oestradiol. After menarche, girls having had menarche before 12 years of age have a more rapid onset of ovulatory menstrual cycles, than girls having later menarche. Significantly higher serum oestradiol and lower sex hormone binding globulin concentrations are seen in women having had early menarche, and the differences still remain at 20-30 years of age. Thus, early menarche is associated with increased oestrogen and progesterone secretion, that might induce a higher degree of breast epithelial proliferation. Further research is required concerning the possible role of physical exercise and nutrition in modifying breast cancer risk.

Adolescent↗
PubMed1995

Metabolic features of polycystic ovary syndrome are found in adolescent girls with hyperandrogenism.

Recently, we reported that hyperandrogenism in adolescent girls is accompanied by augmented LH pulsatility and elevated LH/FSH ratio with increased ovarian volume. Together with higher concentrations of 17-hydroxyprogesterone, androstenedione, testosterone, and estrone that are ovarian in origin, these neuroendocrine features are identical to those seen in adult women with polycystic ovary syndrome. In the present study, we report the metabolic characteristics of these hyperandrogenic adolescent girls. The GH insulin-like growth factor I (IGF-I)-binding protein (BP)-3 axis, insulin sensitivity, and insulin-IGFBP-1/insulin sex hormone binding globulin axes were evaluated in 13 adolescent girls (ages 11-18 yr) with mild to moderate signs of hyperandrogenism (HA) and 28 age-matched normal girls. Insulin sensitivity was assessed by a frequent-sample iv glucose tolerance test (ivGTT, 0.3 g/kg). Twenty-four hour blood samples were obtained at 10-min intervals and were used to determine GH pulsatility (20-min samples), IGFBP-3 levels (0800-0900 h), and fluctuations of insulin, IGFBP-1, and IGF-I (hourly samples) during feeding and fasting phases of the day. In addition, GH responses to GHRH stimulation (1 microgram/kg) were assessed. Fasting insulin concentrations, but not plasma glucose levels, were significantly elevated in the HA group compared with those in the normal group (256 +/- 35 vs. 103 +/- 24 pmol/L, P = 0.0008), as were insulin responses to ivGTT and meals (P < 0.01) and 24-h mean insulin concentrations (P < 0.01). Thus, hyperinsulinemia with normal fasting glucose levels in HA girls may reflect insulin resistance, as suggested by the increased ratio of insulin and glucose (P < 0.001). All measures of insulin were correlated with body mass index (BMI); however, insulin remained significantly higher in the HA group after correcting for BMI, suggesting that decreased insulin sensitivity was related to other factors in addition to BMI. Twenty-four hour IGFBP-1 concentrations showed a diurnal pattern with an inverse relationship to insulin, and 24-h mean concentrations were lower in the HA group (0.35 +/- 0.13 vs. 0.76 +/- 0.09 micrograms/L, P = 0.02). Reduced sex hormone binding globulin levels were also inversely related to insulin levels (P = 0.0007). In contrast, GH pulsatile characteristics and IGF-I/IGFBP-3 levels, as well as GH responses to GHRH, were similar between the groups.(ABSTRACT TRUNCATED AT 400 WORDS)

17-alpha-Hydroxyprogesterone↗
PubMed1994

Accelerated 24-hour luteinizing hormone pulsatile activity in adolescent girls with ovarian hyperandrogenism: relevance to the developmental phase of polycystic ovarian syndrome.

A study was initiated to delineate the neuroendocrine characteristics of hyperandrogenic adolescent girls with the aim of discerning features that may relate to the pubertal onset of the polycystic ovarian syndrome. Thirteen 11- to 18-yr-old girls with mild to moderate signs of hyperandrogenism (HA) and increased ovarian volume and 28 age-matched normal girls were recruited for the study. LH pulsatility and FSH levels were analyzed based on serum concentrations measured with sensitive immunofluorometric assays in samples taken at 10-min intervals for 24 h under basal conditions, GnRH antagonist (Nal-Glu) suppression, and dexamethasone suppression. Adrenal and ovarian contributions to serum cortisol, dehydroepiandrosterone, androstenedione, testosterone (T), estrone (E1), estradiol (hourly), 17-hydroxypregnenolone, and 17-hydroxyprogesterone (17PO) concentrations were compared during basal and suppression conditions and after gonadotropin and adrenal stimulations by bolus GnRH (10 micrograms) and CRF (1 microgram/kg). The progression from sleep-augmented pulsatile LH secretion to higher LH levels during wake than sleep observed during normal pubertal development occurred 2 yr earlier in the HA group. The number of LH pulses was significantly higher in the HA group during both sleep and waking, whereas pulse amplitude was higher only during the awake time. Thus, mean LH was 2.0-fold higher during the awake time and only 1.6-fold higher during sleep in the HA group compared to the normal group. The elevation of FSH in HA was small relative to that of LH, resulting in an increased LH/FSH ratio (P < 0.008). The HA group had higher concentrations of 17PO (1.8-fold), androstenedione (1.9-fold), T (2.4-fold), and E1 (1.7-fold) than the normal group (all P < 0.001), with no alteration in circadian rhythm. These elevated steroid levels were significantly correlated with LH levels in the basal state and decreased in proportion to the change in LH during Nal-Glu suppression. During adrenal suppression with dexamethasone, concentrations of cortisol, dehydroepiandrosterone, and 17-hydroxypregnenolone decreased in both groups (P < 0.001), but significant suppression of 17PO, T, and E1 occurred only in the normal girls, indicating the ovarian origin of the increased levels of these steroids with enhanced expression of 17 alpha-hydroxylase activity in HA girls.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1993

Gonadotrophin releasing hormone pulse generator activity before and during sexual maturation in girls: new insights.

The activity of the gonadotrophin releasing hormone (GnRH) pulse generator during pubertal transition was investigated in 40 healthy girls 7-18 years of age. Ten were pre-pubertal, seven were in early puberty, and 23 were post-menarcheal. Serum concentrations of luteinizing hormone (LH) and follicle stimulating hormone (FSH) were measured with immunofluorimetric assays, which have a sensitivity approximately 100-fold that of radioimmunoassay, in samples taken at 10-min intervals for 24 h during basal conditions, during Nal-Glu antagonist suppression, and in response to GnRH stimulation (10 micrograms). Serum levels of androstenedione, testosterone and oestradiol were measured by radioimmunoassay. Our data show that the GnRH pulse generator is functionally active in prepubertal girls with selective expression of LH and FSH pulses after the onset of sleep. The onset of puberty is associated with a greater increase in LH pulse amplitude than frequency. These overall changes are punctuated by a switch of wake/sleep activities of GnRH pulse generator with a progressive increase in day-time pulsatility and a gradual reduction of sleep-entrained amplification. While LH pulsatility appears to be highly GnRH dependent at all ages, a remarkable decrease in the predominance of GnRH regulation of FSH pulsatility occurs in conjunction with ovarian activation.

Adolescent↗
PubMed1993

Life-long physical activity and cancer risk among Finnish female teachers.

This cohort study on Finnish female teachers of physical education (PE) and languages (L) was performed as an attempt to evaluate the importance of physical activity as a risk determinant of cancer, PE representing a physically active and L a less active subcohort. All the PE and L teachers graduating from 1920 onwards were obtained from four registers compiled from 1958-73 supplemented by an extension cohort drawn from the union membership register 1984-91 (in total 1,499 PE and 8,619 L teachers). Results of a questionnaire to representative samples of L and PE teachers did not reveal any major intergroup differences in social status, general health status, nutrition, maturation history, reproductive history, consumption of alcohol, smoking, or diet. However, the PE teachers reported higher life-long physical activity values than the L teachers. During the follow-up period 1967-91, the number of cancer cases totalled 108 for the PE and 513 for the L teachers. Expected numbers of cancer cases were calculated on the basis of national incidence figures, and the standardized incidence ratios (SIRs) were defined as ratios of observed and expected numbers of cases. The SIR for total cancers was 1.1 for the PE and 1.2 for the L teachers. In both teacher groups the SIRs for cancers of the breast, endometrium, ovary and colon were similarly elevated and the SIR for cervical cancer was reduced. There was an increased SIR for lung cancer (1.4) and skin melanoma (2.0) in the PE but not in the L teachers (0.5 and 0.9, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Activities of Daily Living↗
PubMed1993

Ultrasensitive new immunoassays for gonadotropins in the evaluation of puberty.

The increased sensitivity and specificity of new immunometric gonadotropin assays make them particularly useful to study the ontogenesis of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) secretion in normal and abnormal puberty. The results show that the gonadotropin-releasing hormone pulse generator is functionally active even in prepubertal children with selective occurrence of LH and FSH pulses after the onset of sleep. The onset of puberty is associated with a major increase in pulse amplitude and a small increase in pulse frequency, expressed as a progressive increase in day-time pulsatility, and a gradual reduction of sleep-entrained amplification. Daytime gonadotropin measurements may better distinguish pubertal stages than nighttime sampling because of less overlapping. As the changes are greater with the sensitive assays, the diagnosis of pubertal disturbances is improved. It is easier to differentiate constitutionally delayed puberty and hypogonadotropic hypogonadism, but biologically overlapping phenomena cannot be separated by even sensitive assays. The augmentation of LH secretion after onset of sleep might be missing in hypogonadotropic hypogonadism and is proposed as a new, somewhat complicated, diagnostic approach. As serum concentrations of FSH in prepubertal children are much higher than those of LH, the measurement of FSH in this age group is particularly useful, and lower-than-normal levels can be found in gonadotropin-releasing hormone-independent precocious puberty as well as in pituitary defects.

Adolescent↗
PubMed1993

Gonadotropin-releasing hormone pulse generator activity during pubertal transition in girls: pulsatile and diurnal patterns of circulating gonadotropins.

To delineate the activity of the GnRH pulse generator during pubertal transition, 40 healthy girls 7-18 yr of age were studied. Ten were prepubertal (PP), 7 were in early puberty (EP), and 23 were in late puberty (LP, all postmenarcheal). Serum concentrations of LH and FSH were measured with immunofluorometric assays, which have a sensitivity about 100-fold that of RIA, in samples taken at 10-min intervals for 24 h during basal conditions, during Nal-Glu antagonist suppression, and in response to GnRH stimulation (10 micrograms). Serum levels of androstenedione, testosterone, and estradiol were measured with RIA. A pulsatile pattern of LH and FSH secretion was found in girls of all ages. PP girls had irregular LH pulses with low amplitudes during the daytime, but increased amplitude LH and FSH pulses were evident within 1 h after sleep-onset. Older PP girls had more regular and higher amplitude pulses throughout sleep than younger PP girls. The sleep-related LH and FSH pulses in PP girls were abolished with Nal-Glu GnRH antagonist treatment, reflecting endogenous GnRH pulse activities. The PP group had the most pronounced amplification of LH secretion with sleep yielding a sleep-wake ratio of 4, which decreased to 2 in the EP group and to 1 in the LP group. The emergence of regular daytime LH pulses along with a further amplification of pulsatile activity during sleep was closely related to the onset of breast development. By the age of 16 yr, an LH secretory pattern characteristic of adult women in the early follicular phase, i.e. a decrease in LH concentration during sleep, was established. Mean 24-h LH concentrations increased 40-fold from PP to LP consequent to a 9-fold increase in pulse amplitude and a 4-fold increase in pulse number (both P < 0.0001). Mean FSH concentrations (24 h), which were 20-fold higher than corresponding LH concentrations in the PP group, increased only 3-fold from the PP to the LP group. FSH pulse secretion appears to be predominantly GnRH dependent in PP girls in contrast to girls after ovarian activation, as indicated by the increased FSH responses to both GnRH antagonist suppression and GnRH stimulation in the PP as compared to the EP and LP groups. We conclude that the GnRH pulse generator is functionally active in prepubertal girls with selective expression of LH and FSH pulses after the onset of sleep. The onset of puberty is associated with a greater increase in LH pulse amplitude than frequency.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
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↗