Eugenia Fonseca

Hormone replacement therapy increases ACTH/dehydroepiandrosterone sulfate in menopause

OBJECTIVE To demonstrate that hypoestrogenism in menopause is in part responsible for the decrease in circulating dehydroepiandrosterone sulfate (DHEA-S) and ACTH levels. To test this hypothesis, 25 postmenopausal women aged 47-60 years, were given orally conjugated equine estrogen (CEE) to study the effect on circulating DHEA-S, cortisol and ACTH. DESIGN A prospective, non-blinded study was performed. Hormonal levels were analyzed before and after three cycles of CEE 0.625 mg/day for 21 days followed each by chlormadinone acetate for 5 days. RESULTS Low baseline levels of DHEA-S increased significantly after HRT (1.71+/-0.75 to 3.3+/-1.5 micromol/l, (P<0.001). ACTH levels augmented moderately from 3.26+/-1.4 to 4.7+/-1.8 pmol/l (P<0.05) and cortisol from 350.4+/-118 to 450.8+/-144 nmol/l (P<0.01). A positive correlation was obtained between 17 beta-estradiol and ACTH (r=0.48), estradiol and cortisol (r=0.52) as well as estradiol and DHEA-S (r=0.60). In addition, the correlation was highly significant (P<0.001) between ACTH and DHEA-S at the term of HRT. CONCLUSION HRT increased DHEA-S, ACTH and cortisol concentrations, which may suggest that this therapy may exert a stimulatory effect on the pituitary gland when baseline hypoestrogenism is present, but further studies are required to clarify the mechanism underlying this process.

Low-dose conjugated equine estrogens elevate circulating neurotransmitters and improve the psychological well-being of menopausal women

OBJECTIVE To assess the effect of low-dose conjugated equine estrogens (E) on circulating neurotransmitters and the efficacy for the treatment of psychological symptoms. DESIGN Controlled comparative clinical study. SETTING Endocrine Research Unit, Instituto Mexicano del Seguro Social, Mexico. PATIENT(S) Thirty postmenopausal women received conjugated equine E. Ten women acted as a comparison group. INTERVENTION(S) Conjugated equine E, 0.312 mg/day, for 21 days per cycle during six cycles and added chlormadinone acetate, 2 mg/day, for the last 5 days of each cycle. Green scale for climateric women and Blatt-Kupperman Menopausal Index were used for measuring psychological well-being. MAIN OUTCOME MEASURE(S) Serum levels of dopamine (DA), noradrenaline, serotonin, and beta-endorphin were quantified by specific assays at baseline and at the end of treatment. RESULT(S) Low baseline levels of DA, serotonin, and beta-endorphin increased significantly (P<.001) from 181.9 +/- 47.8 pg/mL to 202.9 +/- 32.8 pg/mL (mean +/- SD); from 206.4 +/- 94.2 ng/mL to 279.2 +/- 67.9 ng/mL; from 11.2 +/- 1.8 pmol/L to 13.8 +/- 2.4 pmol/L, respectively, after conjugated equine E. In parallel, augmented baseline noradrenaline levels diminished significantly (P<.05) from 30.2 +/- 4.7 ng/mL to 24.0 +/- 4.7 ng/mL. All neurotransmitter levels had a significant correlation with 17beta-E(2) concentrations at the end of the study. Alleviation of psychological symptoms was observed in all but eight treated women. CONCLUSION(S) Low-dose conjugated equine E associated with periodic administration of chlormadinone acetate elicited favorable changes in neurotransmitters and relieved psychological symptoms.

Elevation of activity of creatine phosphokinase (CK) and its isoenzymes in the newborn is associated with fetal asphyxia and risk at birth

OBJECTIVE To investigate the relationship of creatine phosphokinase and its isoenzymes with fetal asphyxia and risk at birth. METHODS Thirty-five pregnant women with high-risk pregnancy were studied. RESULTS In 21 patients, fetal distress was diagnosed by interpretation of the fetal heart rate tracing (FHR). The remaining 14 women, having normal fetal cardiotocography, were considered as the control group. Total CK and its isoenzymes activity was measured in cord sera and 24 h after birth in peripheral blood. Abnormal FHR patterns correlate well with elevated enzyme activities. Total CK and its isoenzymes (CK-MM, CK-MB, and CK-BB) exhibited higher values in asphyxiated infants as compared to normal neonates. Electrocardiographic ischemia occurred in seven newborns who had elevated CK-MB and CK-BB levels, both at birth and within 24 h postpartum. Chromatographic study showed in normal neonates that the predominant isoenzyme was CK-MM, whereas CK-BB activity was negligible. In the newborns with abnormal FHR, CK-MB and CK-BB were increased with predominance of CK-MB. CONCLUSIONS Antepartum fetal distress is associated with release of CK-BB, and particularly CK-MB; therefore, these biochemical markers may indicate either brain or myocardial damage.

Feasibility of suppressing and reinitiating lactation in women with premature infants

4 puerperal women (19-33 years of age) who had vaginal deliveries after pregnancies of 34-39 weeks and delivered infants weighing between 1300-2500 gm were treated with 2.5 mg bromocriptine orally 3 times a day from the 1st through the 8th postdelivery days. The infants were under intensive care during this period. None of the patients nursed their infants. Blood samples were obtained during the nonnursing period and assayed for serum prolactin (hPRL) by radioimmunoassay. From Day 8 to 12 postpartum a dose of 20 mg of thyrotropin-releasing hormone (TRH) was administered 4 times a day. Breast-feeding was initiated at the 14th postdelivery day. Serum hPRL levels were suppressed by bromocriptine. Patients were without breast engorgement or milk flow. A bolus dose of 250 mcg TRH exhibited milk flow after TRH injection. Milk production was reinitiated in all the mothers are persisted for the following 4 weeks. These results suggest that the administration of TRH could have some therapeutic value in women for whom it is necessary to suppress and reinitiate lactation.

Usefulness of insulin-like growth factor binding protein-3 levels to determine acromegaly activity and effectiveness of transsphenoidal pituitary surgery.

BACKGROUND Several series reported in the literature concerning the results of the treatment of acromegaly have been difficult to evaluate because the indicators are inaccurate. METHODS We investigated the usefulness of insulin-like growth factor binding protein-3 (IGFBP) levels to determine disease activity after surgical treatment of acromegaly in 13 patients with confirmed somatotroph adenoma. RESULTS Before surgery, all 13 non-treated patients had elevated serum levels of IGFBP-3 as well as total and free IGF-I. In addition, there was no overlap with the normal controls (p < 0.001). IGFBP-3 levels correlated significantly (0.91, p < 0.001) with GH suppressibility by glucose after surgery. CONCLUSIONS These data confirm that IGFBP-3 is a better indicator of acromegalic activity than either total or free IGF-I. There was a high correlation with GH suppressibility by glucose after surgery; both free and total IGF-I could be considered sensitive markers only for diagnosis of active acromegaly but not for efficacy of surgery.

Distribution of growth hormone isoforms in sera from women with normal ovarian function, galactorrhea, and normoprolactinemia *

OBJECTIVE To demonstrate if GH concentrations and molecular heterogeneity of GH correlates with the presence of galactorrhea in normoprolactinemic women with normal ovarian function. DESIGN Aliquots of sera from women with normal ovarian function and normoprolactinemic galactorrhea were subjected to gel filtration chromatography, and the fractions were assayed for GH by the use of radioimmunoassay. Molecular weight of isoforms was calculated on a calibration curve obtained with molecular markers. The molecular variants were characterized on the basis of elution volume, molecular weight (MW), and partition coefficient. RESULTS Basal serum GH levels were moderately elevated in all six normoprolactinemic women exhibiting galactorrhea. Chromatographic study of sera from these normoprolactinemic women showed the predominance of 40 to 50 kd molecular forms of GH as well as some very low MW GH isoforms. This pattern was different from that obtained in sera from normal women without galactorrhea who presented a predominance of heavier (> 60 kd) isoforms eluted before the GH labeled standard. The monomeric forms were present in less proportion but there was no significant difference as compared with galactorrheic group. CONCLUSIONS Our investigation demonstrated elevated GH basal serum levels is normoprolactinemic women with galactorrhea, and chromatography in gel showed a low proportion of the large MW GH variants associated with a higher proportion of the dimeric forms and very low MW forms of GH. This is different from normal women without galactorrhea who had a predominance of heavier MW GH variants and lesser proportion of < 16 kd isoforms. It is concluded that an increased GH secretion may be responsible for abnormal lactation despite normal PRL levels in some women with normal ovarian function.

Gastrin levels in mothers and neonates at delivery in various perinatal conditions

Background. This study was designed to assess the variations of gastrin (Ga) serum levels in mothers and newborns at birth in some perinatal disorders.

Hypergastrinemia of Newborns and Infants During Breast-Feeding

Objective: We determined gastrin concentrations in newborns and their mothers both before and during lactation. Methods: Twenty-five women who had uncomplicated pregnancies with normal vaginal delivery of healthy infants at tem participated in the study. Twelve preterm neonates with low birth weight (LBW) were also studied. Gastrin levels were determined by radioimmunoassay in amniotic fluid and in serum of both the neonates and their mothers at birth and during breast-feeding. Serum levels of gastrin and prolactin (PRL) were measured in the mothers before and after tactile self-stimulation of the breast. Results: In normal newborns, gastrin levels in cord sera were significantly higher than levels in maternal blood and amniotic fluid at birth. However, gastrin cord sera in LBW newborns was lower than in the normal neonates. Nursing resulted in an increment of serum gastrin levels in the infants and mothers; this rise was similar in the 3 postpartum weeks tested. Tactile stimulus of the mothers nipple resulted in increases of both gastrin and PRL. Conclusions: Newborns at term show significantly higher gastrin levels than do LBW neonates, which may indicate differences in development of the gastrointestinal system. Breast-feeding induced gastrin secretion in both mothers and infatns, confirming the presence of an active vagal reflex. In addition, tactile stimulation of the nipple increased gastrin and PRL levels in the mothers. Our data suggest that lBW neonates have deficient production of gastrin, which in turn may indicate an undeveloped gastrointestinal system. An early enteral feeding triggers the postnatal increase in concentrations of gut hormones.

Distribution of follicle-stimulating hormone and luteinizing hormone isoforms in sera from women with primary ovarian failure compared with that of normal reproductive and postmenopausal women**Supported in part by grant P219CCOL880122 from the Consejo Nacional de Ciencia y Tecnología de México, Mexico, D.F., México.

OBJECTIVE To demonstrate if molecular heterogeneity of gonadotropins correlates with the type of primary gonadal failure. DESIGN AND METHODS Aliquots of sera from women with hypogonadism were subjected to gel filtration chromatography to be assayed for follicle-stimulating hormone (FSH) and luteinizing hormone (LH) by the use of radioimmunoassay. Molecular weight (MW) of isoforms was calculated on a calibration curve obtained with molecular markers. The molecular variants were characterized on the basis of elution volume, MW, and partition coefficient. RESULTS Chromatographic profile of sera from four women with natural menopause exhibited two FSH peaks of immunoreactivity and a heavier LH isoform. This pattern was different from that obtained in sera from women of reproductive age who presented a single peak that eluted after the corresponding standard. In six cases of idiopathic premature menopause and three more with gonadotropin-resistant ovary, the chromatographic profile showed a marked and remarkable molecular heterogeneity, particularly LH, and this was more apparent in women with resistant ovary. CONCLUSIONS Our investigation confirms the relationship between the gonadotropin heterogeneity with the gonadal failure. The duration of the ovarian failure may influence the molecular proportion of gonadotropins and the predominance of heavier MW isohormones.