Rosita Gallo

Ultrasonographic bone characteristics during normal pregnancy: Longitudinal and cross-sectional evaluation

OBJECTIVE We evaluated the pattern of bone density during pregnancy by radiation-free ultrasonographic densitometry. STUDY DESIGN In a longitudinal study we measured bone mineral density in a group of 10 normal primiparous women, from the fourteenth to the thirty-eighth weeks of pregnancy. In a cross-sectional study bone mineral density was determined in a group of 85 normal primiparous women, in different weeks of pregnancy. RESULTS In the longitudinal study ultrasonographic bone density was stable in the first part of pregnancy, whereas a significant (p < 0.05) decrease was evidenced during the third trimester. A negative correlation between bone density and weeks of pregnancy (p < 0.0001) was evidenced in the cross-sectional study. CONCLUSION During physiologic pregnancy the calcium mobilization from the maternal bone stores to accomplish the fetal needs can cause a significant decrease in maternal bone density in the last trimester of gestation.

Menopause and the central nervous system: intervention options.

The central nervous system is an important target for sex steroid hormones. During the climateric period the rapid decline of gonadal steroids causes neuroendocrine changes in different areas of the brain. The failure of gonadal hormone production brings specific symptoms due to the central nervous system derangement. At the hypotalamic level estrogen withdrawal gives rise to vasomotor symptoms, eating behavior disorders and altered blood pressure control. Psychological disturbances such as depression, anxiety, irritability and mood fluctuation are related to estrogen-induced changes in the lymbic system. The hypothesis of specific neuroanatomical and neurophysiological effects of estrogen on the brain may also explain the correlation between estrogen deficiency and cognitive disturbances such as Alzheimers type dementia (AD). The increasing interest in the influence of sex steroids on brain function has focused attention on hormonal replacement therapy. Clinical and epidemiological studies have demonstrated that estrogen therapy exerts a positive effect on vasomotor instability and improves psychological disturbances. The positive effects of estrogen on mood are probably related to its stimulatory action on adrenergic and serotoninergic tone. Estrogen may influence the cognitive function through different biological actions. Estrogen administration increases total cerebral and cerebellar blood flow, cerebral glucose administration and improves cholinergic tone, a key neurotransmitter in learning and memory. The evidence suggests that hormone replacement therapy may reduce the relative risk of developing AD. Progestagens and androgen may also have a role in the control of mood disorders. At present, few data are available regarding the influence that selective estrogen receptor modulators, a new class of compounds, can exert on the brain.

Corticotropin-Releasing Factor-Binding Protein: Origins and Possible Functions

Corticotropin-releasing hormone-binding protein (CRFBP) is a 37-kD protein of 322 amino acids, containing one putative N-glycosylation site and 11 cysteines, 10 of which remain in the mature molecule (298 amino acids) and result essential for the action. CRFBP protein gene has been cloned and mapped to the distal region of chromosome 13 and loci5q in the mouse and human genomes. CRFBP is the only example of a neuropeptide-binding protein. It is produced in human and rat brain, and in human liver and placenta. In brain, the central distribution of CRFBP shares some regional overlap with CRF receptor-bindings sites. Additionally, in hypothalamic and limbic structures, CRFBP has been identified in association with CRF-expressing cell groups. CRFBP has been also demonstrated in the human placenta and related membranes. Indeed, amniotic epithelium, chorionic cytotrophoblast, and maternal decidua also show intense positive CRFBP mRNA signals. Circulating CRFBP levels in healthy nonpregnant individuals show the same range values as in maternal plasma collected during the first and second trimesters of pregnancy. A rise in CRFBP levels at 30-35 weeks of pregnancy with a dramatic decrease at 38-40 weeks have been shown. At postpartum, CRFBP levels in maternal plasma reach the nonpregnant concentrations. Recombinant and native CRFBP neutralize the ACTH-releasing activity of human CRF in cultured pituitary or placental cells and, additionally, may block the activity of CRF on human pregnant endometrium prostaglandin release and on human myometrium contractility in vitro. These findings suggest that CRFBP may play a role in modulating the functions of CRF in human pregnancy.

Cyclic-combined Conjugated Estrogens and Dydrogesterone in the Treatment of Postmenopausal Syndrome

We report the data concerning postmenopausal women treated either with a calcium supplement (500 mg/day, group l, n = 13) or with cyclic conjugated estrogens (0.625 mg/day) and dydrogesterone (5 mg/day) for 21 days with a 7-day free interval (n = 27, group 2) for 24 months. Withdrawal bleeding was regular, starting 1–2 days after the last treatment day and defined as light or mild. No sign of endometrial hyperstimulation was found by hysteroscopy and endometrial biopsy performed after 24 months of treatment. In group 1, constant levels of both urinary excretion of hydroxyproline and plasma osteo-calcin were observed, along with a significant (p < 0.05) decrease in vertebral bone mineral density. In group 2, both urinary excretion of hydroxyproline and plasma osteocalcin levels were significantly (p < 0.05) decreased and vertebral bone density showed a slight but significant (p < 0.05) increase. In group 1, a significant (p < 0.05) increase in serum low-density lipoprotein (LDL)-cholesterol levels was observed, whereas no modification in total cholesterol, high-density lipoprotein (HDL)-cholesterol and triglycerides was found. In group 2, total cholesterol and LDL-cholesterol levels significantly (p < 0.05) decreased, whereas triglycerides levels were stable throughout the study. In this group, HDL-cholesterol levels showed a significant (p < 0.05) increase. In conclusion, the regimen for cyclic combined estrogen-progestogen therapy attenuates bleeding disturbances and results in a low dropout rate. Thus, the clinical and metabolic actions, as well as the protective effects on the endometrium, make this treatment of potential interest. Further studies are required to confirm the long-term beneficial effects of this formula on cardiovascular protection and fracture rate.

Hormonal Replacement Therapy, Cognitive Disturbances, and Alzheimer’s Disease

Sex steroid hormones modulate the synthesis and release of neurotransmitters and neuropeptides through the binding with specific receptors in the central nervous system (CNS). In the last ten years, several epidemiological and clinical studies have shown an impairment of psychological and cognitive functions in postmenopausal women. The withdrawal of ovarian steroid production and neuroendocrine modifications have been directly related to an alteration of the cognitive function. Clinical studies have shown that hormone replacement therapy (HRT), especially that of estrogen, plays an important role in enhancing and maintaining short-term memory and abstract reasoning in postmenopausal women, whereas the performance of nontreated postmenopausal women decreases. The most severe decline of cognitive functions occur in Alzheimer’s disease (AD) patients. The incidence of AD is higher in women than in age-matched men and the cognitive function impairment is more pronounced in women than in men. An impairment of the cholinergic neuroendocrine system is involved in the pathogenesis of cognitive disturbances and of AD due to a reduction of choline acetyltransferase activity. Cholinergic pathway modifications occur in postmenopausal women with the cessation of ovarian activity. Experimental and clinical trials suggest that estrogen reverses the decrease of choline acetyltransferase in postmenopausal women, enhances cognitive functions, and may prevent the incidence of AD. Recent studies have demonstrated that glial cells and neurons are able to synthesize neuroactive steroids, starting from cholesterol, as well as metabolizing steroid hormones originating in the adrenal gland. Neurosteroids are active in modulating stress adaptive responses and memory.

Changes of Activin A Secretion in Gestational Diseases

Among the various tissues producing inhibin, activin, and follistatin, the gestational intrauterine tissues—placenta, decidua, and fetal membranes-have a major interest. A possible functional involvement of these proteins in reproductive physiology has been suggested. Inhibin and activin act within the human placenta through a cell-to-cell communication (paracrine) or within the same cells (autocrine), locally modulating placental hormonogenesis, cell-mediated immune function, and growth and differentiation of embryo and fetus. In addition, inhibin and activin may also enter the maternal and fetal circulation and have an endocrine effect in the physiology of pregnancy. The changes of activin and inhibin concentration in gestational biological fluids (maternal serum, umbilical cord serum, and amniotic fluid) thus reflect the changes of placental inhibin and activin synthesis and secretion.