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LH and FSH Levels for Samples Collected From Premature Neonates Born Between 24 and 29 Weeks' Gestation
Source publication
Establishing pediatric reference intervals has always been challenging, with most ranges used in pediatric laboratories developed over many years. The clinical interpretation of gonadotropins is important in the context of ambiguous genitalia. The aim of this study was to develop reference intervals for luteinizing hormone and follicle-stimulating...
Contexts in source publication
Context 1
... results obtained from the 43 male samples dem- onstrated a range of LH results from 0.1 to 13.4 IU/L (median: 1.7 IU/L; n 39) and a range of FSH results from 0.3 to 4.6 IU/L (median: 1.2 IU/L; n 29; Table 1). Of the 10 LH results 4 IU/L, 5 were collected at 0 days of age (cord blood samples), 3 were collected at 1 day of age, 1 from 7 days of age, and 1 from a 14-day- old infant. ...
Context 2
... equivalent rise is not evident for FSH with the ratio for these 10 samples all 2.0 ( Fig 1). Therefore, because of the higher levels evident in cord blood samples, the results from cord blood and 1-day- old infants were separated and compared with the results from samples of older infants (4 -43 days of age; Table 1). ...
Context 3
... the obvious difference in LH and FSH concen- trations between the 2 sets of results, the ratios of LH/FSH were consistent between the cord day-1 and day-4 to -43 groups ( Table 1). The ratio of LH/FSH was calculated (n 25) and showed a median ratio of 2.3 with the ratio rang- ing from 0.3 to 3.9 with 2 high outliers demonstrated on the box-and-whisker plot (Fig 3). ...
Citations
... The highest elevation of LH was observed by the end of first month in both groups; with the magnitude being greater in PT infants (12.7 µIU/mg vs 5 µIU/mg). An earlier Australian study established reference ranges for serum LH and serum FSH in premature newborns till 43 days after birth [10]. The mean LH levels were higher in PT infants in the present study in comparison to the earlier study [10]. ...
... An earlier Australian study established reference ranges for serum LH and serum FSH in premature newborns till 43 days after birth [10]. The mean LH levels were higher in PT infants in the present study in comparison to the earlier study [10]. Different ethnicity and assays may be the reason for this discrepancy. ...
... However, from first to third month, PT infants had significantly higher FSH levels. The mean FSH levels observed at first month were significantly higher in PT males in this study as compare to another study (5 µIU/ mg vs 1.1 µIU/mg) [10]. There was a steady decline in FSH levels among FT infants reaching pre-pubertal values by six months (i.e. ...
To study the differences in the timing and magnitude of postnatal urinary gonadotropins and testosterone secretion during minipuberty in Indian preterm (PT) and full-term (FT) male infants.
This prospective observational study included 30 PT and 60 FT male infants. Urinary luteinizing hormone (LH), follicular stimulating hormone (FSH), and testosterone, and stretched penile length (SPL) and testicular volume (TV) were measured on day 7, first month, second month, fourth month and at six months of age.
The highest elevation of mean (SD) urinary LH was observed in PT infants in comparison to FT infants [12.6 (1.4) vs 4.9 (0.6) µIU/mg, respectively; P < 0.001] in the first month. FSH levels were lower in PT than FT infants on day 7 (P < 0.001). Testosterone was significantly elevated in PT than FT infants [70.8 (5.6) vs 44.6 (3.2) ng/mg; P < 0.001] with a greater mean percentage increase in SPL (P < 0.001) and TV (P < 0.001) by the first month.
Indian PT male infants showed a greater increase in urinary LH and testosterone, with a faster increase in SPL and TV.
... Based on recent longitudinal studies using urinary gonadotropins (uGns), preterm (PT) birth does not seem to influence the onset of postnatal HPG axis activation, as gonadotropin levels begin to rise with the same timing in full-term (FT) and PT infants (1). Moreover, minipuberty in PT babies seems to be stronger and prolonged with uncertain significance and effects (30,31,32) but data are still not univocal. ...
... The influence of prematurity on sexual hormone levels has been investigated by few studies, mainly cross-sectional and with slightly different findings (30,31,32). Only one study with a longitudinal design (7) found higher uLH and uT levels in PT boys, as well as an increase in T levels in all neonates with a peak at one month and a positive correlation with penile growth. ...
Objective:
The postnatal activation of the hypothalamic-pituitary-gonadal(HPG) axis is usually known as "minipuberty". There are still open questions on its biological activity and significance depending on sex, gestational age(GA) and birth weight(BW) with few longitudinal data.
Methods:
Single-centre longitudinal study to quantify urinary FSH(uFSH), LH(uLH) and testosterone(uTs) in male neonates. 46 neonates were enrolled and sorted into 3 subgroups: 23 full-term boys appropriate for GA(FT AGA), 11 full-term boys with BW≤3 rd centile(FT SGA), and 12 preterm(PT) boys≤33 weeks of GA. Urinary hormones were measured with electrochemiluminescence immunoassay and correlated to simultaneous auxological parameters, linear growth and external genitalia at scheduled time-points.
Results:
PT boys display a pulsatile pattern of urinary gonadotropins(uGns) with higher levels of uLH and a gradual increase of uTs. Testicular descent starts from 29-32weeks with the peak of uTs. During the first 12-months post term age(PTA), FT AGA boys display a better linear growth(p<0.05). PT show higher uGns levels until 3-months PTA. Considering chronological age, PT babies in the first 90 days of life have higher uLH levels than FT AGA with a peak at 7 and 30 days(p<0.001) and higher uTs levels. Correlation analysis between penile growth of all neonates and uTs is significant(p=0.04) but not when subgrouping.
Conclusions:
This study provides valuable information on the postnatal HPG axis activation in term and preterm infants. Minipuberty may involve an early window of opportunity to evaluate the HPG axis functionality. Further studies with a long-term follow-up are needed with a special focus on possible consequences of GA and BW.
... A blood sample was taken from each patient at approximately 10 weeks of age to evaluate FSH and LH from the serum samples of all patients and to evaluate 17-beta estradiol (E2) and testosterone levels, respectively, from the serum samples of female and male patients. Results: It was found that minipuberty occurred in the case group patients, with no significant differences reported from the control group and with hormonal serum levels comparable to healthy infants of the control group (FSH 4.14 mUI/ml ± 5.81 SD vs. 3.45 mUI/ml ± 3.48 SD; LH 1.41 mUI/ml ±1.29 SD vs. 2.04 mUI/ml ±1.76 SD; testosterone in males 0.79 ng/ml ± 0.43 SD vs. 0.56 ng/ml ± 0.43 SD; 17-beta estradiol in females 28.90 pg/ml ± 16.71 SD vs. 23.66 pg/ml ± 21.29 SD). ...
... Data from the literature revealed that the surge in FSH and LH levels was higher and prolonged in preterm infants than in fullterm infants, especially in females (21)(22)(23). Kuiri-Hänninen et al. compared full-term and preterm males by measuring urinary gonadotropin levels and testosterone levels in serial urine samples and comparing the results with testicular and penile growth. The trends in LH and testosterone secretion levels were found to be significantly higher in preterm than in full-term infants (12). ...
... The trends in LH and testosterone secretion levels were found to be significantly higher in preterm than in full-term infants (12). A study by Greaves et al., which analyzed LH and FSH levels in a population of 82 premature infants born under a 30-week gestation, reported that prematurity was related to significantly high gonadotropin levels in girls (LH levels from 0.1 to 13.4 IU/L and FSH levels from 0.3 to 4.6 IU/L in male preterms vs. LH levels from 0.2 to 54.4 IU/L and FSH levels from 1.2 to 167.0 IU/L in female preterms) (23). These hormonal patterns may reflect an immaturity of the negative feedback system in the HPG axis, and the highest levels of FSH in preterm females may be attributed to immature ovaries that do not seem to be capable of producing estrogen of sufficient quantity that will inhibit the secretion of gonadotropin. ...
IntroductionThe aim of our single-center case–control study is to evaluate whether minipuberty occurs in patients with hypoxic ischemic encephalopathy (HIE) who underwent therapeutic hypothermia (TH). We intend to conduct this evaluation by confronting the values of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) and the values of testosterone in males and estradiol in females between newborns with HIE and in subsequent TH and healthy controls.Methods
We enrolled 40 patients (age: 56–179 days; 23 males), of whom 20 met the inclusion criteria for the case group and who underwent TH. A blood sample was taken from each patient at approximately 10 weeks of age to evaluate FSH and LH from the serum samples of all patients and to evaluate 17-beta estradiol (E2) and testosterone levels, respectively, from the serum samples of female and male patients.ResultsIt was found that minipuberty occurred in the case group patients, with no significant differences reported from the control group and with hormonal serum levels comparable to healthy infants of the control group (FSH 4.14 mUI/ml ± 5.81 SD vs. 3.45 mUI/ml ± 3.48 SD; LH 1.41 mUI/ml ±1.29 SD vs. 2.04 mUI/ml ±1.76 SD; testosterone in males 0.79 ng/ml ± 0.43 SD vs. 0.56 ng/ml ± 0.43 SD; 17-beta estradiol in females 28.90 pg/ml ± 16.71 SD vs. 23.66 pg/ml ± 21.29 SD).DiscussionThe results of the present study may pave the way for further research and the evaluation of more possible advantages of TH.
... Circulating FSH concentrations in female fetuses are high at mid-gestation, then decrease to low levels at birth, but transiently increase again during postnatal pituitary activation 27 . In premature girls, extremely high postnatal levels of FSH have been described, indicating an alteration in pituitary-ovarian function in infancy 27,28 . ...
One of the most common malformations of the central nervous system is related to embryonic neural tube alterations. We hypothesized that anencephaly affects the development of the uterus during the human second trimester of pregnancy. The objective of this study was to study the biometric parameters of the uterus in fetuses with anencephaly and compare them with normocephalic fetuses at that important. In our study, 34 female fetuses were analyzed, 22 normal and 12 anencephalic, aged between 12 and 22 weeks post-conception (WPC). After dissection of the pelvis and individualization of the genital tract, we evaluated the length and width of the uterus using the Image J software. We compared the means statistically using the Wilcoxon-Mann–Whitney test and performed linear regression. We identify significant differences between the uterus length (mm)/weight (g) × 100 (p = 0.0046) and uterus width (mm)/weight (g) × 100 (p = 0.0013) when we compared the control with the anencephalic group. The linear regression analysis indicated that 80% significance was found in the correlations in normocephalic fetuses (12.9 to 22.6 WPC) and 40% significance in anencephalic fetuses (12.3 to 18.6 WPC). The measurements of the uterus were greater in anencephalic group but there are no difference in the uterine width and length growth curves during the period studied. Further studies are required to support the hypothesis suggesting that anencephaly may affect uterine development during the human fetal period.
... Still, HPG axis activation in the extremely premature infants is increased and prolonged, resulting in higher sex steroid hormone concentrations in preterm babies [2]. Reference data based on serum measured in 82 preterm babies for LH and FSH showed higher levels of gonadotropins in preterm infants than in full-term infants [9]. This was confirmed in a study that showed that estradiol levels were significantly higher in preterm than in full-term girls. ...
Introduction. Minipuberty occurs during the first months of life after the activation of the hypothalamic-pituitary-gonadal axis which causes an increase in gonadotropic and sex hormones. Usually, it does not induce clinically evident physical changes. Studies have shown that minipuberty in extremely premature infants is more pronounced and lasts longer, leading to higher levels of sex hormones induce climically evident in physical changes. Case Report. We present two extremely premature female infants, born at 25 weeks of gestation, with clinically evident physical changes during minipuberty. The first infant presented with vaginal bleeding at the age of 4 months, corrected age of 2 weeks. The vaginal bleeding lasted for two days and stopped spontaneously. The infant also had small glandular breast buds of 1 cm bilaterally, swelling in the pubic region, swollen vulva and clitoris. The second infant presented with swelling in the genital region, suprapubic area and the anterior part of thighs, at the age of 4 months, corrected age of 2 weeks. Both infants had ovarian cysts. In both cases, laboratory tests were consistent with minipuberty. The described changes disappeared gradually and spontaneously. Conclusion. In order to avoid unnecessary testing, clinicians should be aware of possible physical changes during minipuberty in extremely premature infants. Clinical monitoring of these infants is recommended until regression of newly developed physical characteristics.
... Afterwards, the FSH concentrations gradually decrease within 4 months to the prepubertal range, while FSH level remains elevated in females until 3-4 years of age [36,37]. Elevated LH levels were detected in the preterm population [38,39]. Based on our findings, breast milk produced for preterm infants has higher LH concentration compared to term milk. ...
... As found by previous investigators [38,39], we found elevated levels of LH in the breast milk of mothers who delivered prematurely compared to term milk. Movsas and coworkers observed that elevated plasma LH is associated with the development of retinopathy of prematurity in female preterm infants but not male infants [39]. ...
Hormones are important biological regulators, controlling development and physiological processes throughout life. We investigated pituitary hormones such as follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL) and total protein levels during the first 6 months of lactation. Breast milk samples were collected every fourth week of lactation from mothers who gave birth to preterm (n = 14) or term (n = 16) infants. Donor milk is suggested when own mother’s milk is not available; therefore, we collected breast milk samples before and after Holder pasteurization (HoP) from the Breast Milk Collection Center of Pécs, Hungary. Three infant formulas prepared in the Neonatal Intensive Care Unit of the University of Pécs were tested at three different time points. Our aim was to examine the hormone content of own mother’s milk and donor milk. There were no significant changes over time in the concentrations of any hormone. Preterm milk had higher PRL (28.2 ± 2.5 vs 19.3 ± 2.3 ng/mL) and LH (36.3 ± 8.8 vs 15.9 ± 4.1 mIU/L) concentrations than term milk during the first 6 months of lactation. Total protein and FSH concentrations did not differ between preterm and term breast milk. Holder pasteurization decreased the PRL concentration (30.4 ± 1.8 vs 14.4 ± 0.6 ng/mL) and did not affect gonadotropin levels of donor milk. Infant formulas have higher total protein content than breast milk but do not contain detectable levels of pituitary hormones. Differences were detected in the content of pituitary hormones produced for preterm and term infants. Divergence between feeding options offers opportunities for improvement of nutritional guidelines for both hospital and home feeding practices.
... Moreover, this hormonal surge might be even stronger and more prolonged than in FT infants (40,41). However, these data are not univocal (40)(41)(42) in either the amplitude or the duration between different sexes. Immaturity of the hypothalamic feedback has been suggested as a possible mechanism for this strong and prolonged activation, although its biological significance is still not completely understood. ...
Hypothalamic-pituitary-gonadal (HPG) axis activation occurs three times in life: the first is during fetal life, and has a crucial role in sex determination, the second time is during the first postnatal months of life, and the third is with the onset of puberty. These windows of activation recall the three windows of the “Developmental Origin of Health and Disease” (DOHaD) paradigm and may play a substantial role in several aspects of human development, such as growth, behavior, and neurodevelopment. From the second trimester of pregnancy there is a peak in gonadotropin levels, followed by a decrease toward term and complete suppression at birth. This is due to the negative feedback of placental estrogens. Studies have shown that in this prenatal HPG axis activation, gonadotropin levels display a sex-related pattern which plays a crucial role in sex differentiation of internal and external genitalia. Soon after birth, there is a new increase in LH, FSH, and sex hormone concentrations, both in males and females, due to HPG re-activation. This postnatal activation is known as “minipuberty.” The HPG axis activity in infancy demonstrates a pulsatile pattern with hormone levels similar to those of true puberty. We review the studies on the changes of these hormones in infancy and their influence on several aspects of future development, from linear growth to fertility and neurobehavior.
... 3,4 On the other hand, in preterm babies, immaturity of HPG axis and sudden decrease in levels of placental sex steroid results in disrupted negative feedback mechanism, increased gonadotropin levels, ovarian hyperstimulation causing cysts and very high levels of E 2 which altogether result in POHS. 5 Since it is not seen in all preterm babies, it is postulated that other mechanisms play a role in POHS pathogenesis. In ovarian hyperstimulation syndrome (OHSS) seen in adult females and characterized by ovarian follicular cysts, generalized edema and increased levels of gonadotropins and E 2 ; three mechanisms are held responsible: gestational spontaneous OHSS which is the result of increased placental production of endogenous hCG, iatrogenic OHSS caused as a complication of drugs used for in vitro fertilization and OHSS caused by increased hCG/LH sensitivity because of FSH receptor mutation. ...
... 15,16 This is explained by decreased sensitivity of peripheral E 2 receptors as a result of immature gonadal axis. 5,15,16 In our case, stage 2 thelarche, increased size of uterus and increased endometrium thickness were detected. These different clinical presentations support the idea that sensitivity of peripheral E 2 receptors can vary among people. ...
Background:
Preterm ovarian hyperstimulation syndrome (POHS) is an uncommon disorder characterized by prematurity, hypogastric and upper leg swelling, high serum estradiol and gonadotropin levels, and ovarian cysts. Immaturity of the gonadal axis is accepted as the cause. But still, other etiological factors are suspected.
Case:
A preterm baby who was born at 24 gestational weeks was referred to our clinic for ambiguous genitalia on day 118 of life. Labia majora and clitoris was edematous. Clitoris length was 1.5 cm. On laboratory evaluation: 17OH-Progesterone: 1.84 ng/ml, dehydroepiandrosterone sulphate (DHEA-S): 139 μg/dl, total testosterone (T.T): 88 ng/dl, luteinizing hormone (LH): 22.5 mIU/l, Follicle stimulating hormone (FSH): 15.7 mIU/l, estradiol (E2): 447 pg/ml. Karyotype analysis was 46, XX. There was a 25x14x12 mm ovarian cyst detected on ultrasound. On follow-up, E2 levels and cyst size increased, and there was 4 mm pericardial effusion on echocardiography at the time.
Conclusion:
In this paper, we present a case with POHS and to discuss possible pathophysiological mechanisms and treatment. This is the first case of POHS developing pericardial effusion.
... Data on hormonal changes in minipuberty in preterm babies are scarce. Reference data based on serum measurements in 82 preterm babies for LH and FSH (measured by immunochemiluminometric assay [ICMA]) showed higher values for gonadotropins in preterm infants than in full-term infants, and higher LH and FSH values in preterm girls than in preterm boys [20]. This was confirmed by a study based on serial urinary measurements (using time-resolved immunofluorometric assay [TR-IFMA]) [21]. ...
Minipuberty describes the transient sex-specific activation of the hypothalamic-pituitary-gonadal (HPG) axis during the first 6 months of life in boys and during the first 2 years in girls. It leads to a rise of luteinizing hormone, follicle-stimulating hormone, estradiol, and testosterone. The existence of minipuberty has been known for >40 years, but we still do not fully understand why it takes place. Current thinking suggests that it is an essential imprinting period for different body functions. Firstly, minipuberty plays an important role in genital organ development; testosterone influences penile growth, the number of Sertoli cells, and spermatogenesis. Secondly, it seems to influence the infant's body composition; testosterone likely has an imprinting effect on BMI and body weight of boys and growth velocity in the first 6 months of life. Thirdly, it affects cognitive functions; testosterone has an impact on language organization in the infant brain and estradiol affects laryngeal sound production and baby babbling. There are inconsistent findings concerning the impact of minipuberty on sex-specific playing behavior. Minipuberty is an interesting field of research, and further studies in this area will teach us more about this exciting period of human development.
... Based on prior reports of high LH in preterm infants, 34 we were not surprised to find high LH levels in our study population. However, we had expected to find higher LH levels in the no-ROP group compared to the NP-ROP group. ...
Background:
Human chorionic gonadotropin (hCG) and luteinizing hormone (LH) are pro-angiogenic gonadotropic hormones, which classically target the reproductive organs. However, hCG, LH, and their shared CG/LH receptor are also present in the human eye. The possibility that a deficiency of these hormones may be involved in the pathogenesis of retinopathy of prematurity (ROP) during its early non-proliferative phase has not been explored.
Methods:
We conducted a cross-sectional study of Michigan-born preterm infants utilizing dried blood spots. We analyzed hCG and LH blood levels at 1 week and 4 weeks of age from 113 study participants (60 without ROP; 53 with non-proliferative ROP). We utilized electrochemiluminescence assays on the Mesoscale Discovery platform.
Results:
Similar levels of hCG are found in preterm infants at both 1 week and 4 weeks after birth. Preterm infants with non-proliferative ROP, after adjusting for sex and gestational age, have 2.42 [95% CI: 1.08-5.40] times the odds of having low hCG at fourth week of age.
Conclusions:
We found that hCG is present postnatally in preterm infants and that a deficiency of hCG at 4 weeks of age is potentially associated with non-proliferative ROP. This provides novel evidence to suggest that hCG may participate in human retinal angiogenesis.
