Costantino Di Carlo

Effects of postmenopausal hypoestrogenism on skin collagen

OBJECTIVE The aim of our study was to evaluate the effect of aging and postmenopausal hypoestrogenism on skin collagen content. METHODS Thirty-two women (mean age 48.78 +/- 9.86; year +/- S.D., range 28-68), 14 in premenopause and 18 in postmenopause, underwent skin biopsies performed during laparotomic operation. The amount of collagen type I, III and type III/type I ratio was evaluated by immunohistochemistry and computerised image analysis, and was related to age and years of postmenopause. RESULTS In the postmenopausal patients, a significant (P < 0.01) decrease of percentage of skin collagen type I, type III and type III/type I ratio was observed in comparison to premenopausal women. The percentages of collagen type I, type III and type III/I ratio of all patients studied was significantly (P < 0.01) correlated with chronological age (r = 0.88, 0.89 and 0.61, respectively). Considering only postmenopausal subjects, the correlation with chronological age was significant (P < 0.01) for collagen type I and type III of postmenopausal women (r = 0.59, r = 0.64, respectively), but not for the type III/I ratio (r = 0.37, P = 0.131). The percentages of collagen type I, type III and type III/I ratio of postmenopausal women showed a significant (P < 0.01) inverse correlation with years of postmenopause (r = 0.76, 0.73 and 0.73, respectively). CONCLUSIONS Our data suggest that the decrease of skin collagen is an estrogen-related phenomenon.

MATERNAL SERUM AND UMBILICAL CORD BLOOD LEPTIN CONCENTRATIONS WITH FETAL GROWTH RESTRICTION

OBJECTIVE To ascertain whether fetal growth restriction is associated with alterations of leptin concentrations in umbilical cord blood and maternal serum. METHODS Maternal serum and umbilical cord blood leptin concentrations were determined by immunoradiometric assay at term in 43 women with uncomplicated singleton pregnancies (group A) and in 27 women with singleton pregnancies complicated by fetal growth restriction (group B), all with normal pregravid body mass index (BMI). RESULTS Maternal serum leptin concentrations were significantly higher in group B compared with group A (45.0 ng/mL [range 34.2–54.9] versus 29.0 ng/mL [range 24.7–33.3]; P < .01). Umbilical cord blood leptin levels were significantly lower in group B compared with group A (8.4 ng/mL [range 3.6–13.2] versus 13.1 ng/mL [9.7–16.5]; P < .01). Maternal serum leptin levels were not significantly correlated with maternal BMI or with neonatal birth weight in either group. Umbilical cord blood leptin concentrations were significantly correlated with neonatal birth weight in both groups. CONCLUSION Growth restricted fetuses at term show umbilical cord blood leptin concentrations significantly lower than those in normal fetuses, suggesting that fetal adipose tissue is a major source of leptin. Maternal serum leptin concentrations are higher in the presence of a growth restricted fetus. This increase might be due to an intrinsic placental mechanism, by which small placentas produce more leptin as a compensatory mechanism, or to early hypoxia.

Is it possible to run a successful ovulation induction program based solely on ultrasound monitoring? The importance of endometrial measurements

OBJECTIVE To attempt the monitoring of ovulation induction solely with ultrasound (US). DESIGN Using serial US measurements to monitor ovulation induction using human menopausal gonadotropin and human chorionic gonadotropin (hCG), in comparison with estradiol (E2) concentrations that became available at the end of each cycle. SETTING Specialist Reproductive Endocrine Unit. PATIENTS, PARTICIPANTS Twenty hypogonadotropic and 29 ultrasonically diagnosed polycystic ovary patients. MAIN OUTCOME MEASURE Follicular growth, uterine measurements, endometrial thickness, and serum E2 concentrations. RESULTS Follicular growth, uterine measurements, and endometrial thickness correlated strongly with E2 concentrations (P less than 0.0001). The endometrium on the day of hCG administration was significantly thicker (P less than 0.01) in the conception (n = 27) compared with the nonconception cycles (n = 87), whereas no significant difference were observed in serum E2 concentrations. No pregnancy was observed when hCG had been administered when the endometrial thickness was less than or equal to 7 mm. Midluteal endometrial thickness of greater than or equal to 11 mm was found to be a good prognostic factor for detecting early pregnancy (P less than 0.008). CONCLUSIONS Serial US examinations used alone have proven to be safe and highly efficient. It also has a unique ability to detect pregnancy in the midluteal phase.

Metalloproteinases, vascular endothelial growth factor, and angiopoietin 1 and 2 in eutopic and ectopic endometrium

OBJECTIVE To evaluate the expression of vascular endothelial growth factor (VEGF), angiopoietin 1 and 2 (ANGPT1/ANGPT2), and matrix metalloproteinases 1, 2, and 9 (MMP-1, MMP-2, MMP-9) in eutopic and ectopic endometrium. DESIGN Experimental retrospective study. SETTING University hospital. PATIENT(S) Eutopic and ectopic endometrium samples from 30 women with endometriosis and endometrium biopsy samples from 30 healthy women. INTERVENTION(S) Biopsies of ovarian endometriomas and eutopic endometrium. MAIN OUTCOME MEASURE(S) Immunohistochemical staining to evaluate the expression of VEGF, ANGPT1, ANGPT2, MMP-1, MMP-2, and MMP-9, and real-time polymerase chain reaction analysis to quantify mRNA expression. RESULT(S) Patients with endometriosis had higher levels of angiogenic factors and metalloproteinases in endometriotic cysts than in eutopic endometrium. These substances were also overexpressed in eutopic endometrium of patients with endometriosis when compared with normal controls. CONCLUSION(S) Overexpression of angiogenic factors and metalloproteinases may be the characteristic feature of endometrium with greater potential to transform into endometriotic lesions in the peritoneal cavity. Structural and/or functional differences of eutopic endometrium could have a role in the pathogenesis of endometriosis secondary to the backward passage of endometrial cells into the peritoneal cavity. Whether these local factors may induce, promote, and/or regulate this transformation remains to be determined.

Hormonal contraception and bone metabolism: a systematic review

BACKGROUND Although a large amount of studies in the literature evaluated the effects of hormonal contraception on bone, many questions remained still unclear, such as the effect of these therapies on fracture risk. STUDY DESIGN We performed a systematic search of the published studies from January 1975 through January 2012 on the effects of hormonal contraceptives on bone metabolism. We analyzed the overall effect on bone mineral density (BMD) and on fracture risk of combined oral contraceptives (COCs), progestogen-only contraceptives, transdermal contraceptives and vaginal ring. RESULTS COC therapy does not seem to exert any significant effect on BMD in the general population. In adolescents, the effects of COCs on BMD seem to be mainly determined by estrogen dose. The use of COCs in perimenopausal women seems to reduce bone demineralization and may significantly increase BMD even at a 20-mcg dose. Use of depot medroxyprogesterone acetate is associated with a decrease in BMD, although this decrease seems to be partially reversible after discontinuation. Data on other progestogen-only contraceptives, transdermal patch and vaginal ring are still limited, although it seems that these contraceptive methods do not exert any influence on BMD. CONCLUSIONS Hormonal contraceptives do not seem to exert any significant effect on bone in the general population. However, other randomized controlled trials are needed to evaluate the effects on fracture risk since the data available are derived from studies having the effects on BMD as the primary end point, and BMD may not accurately reflect the real fracture risk.

Use of leuprolide acetate plus tibolone in the treatment of severe premenstrual syndrome

OBJECTIVE To evaluate the effectiveness of GnRH agonist (GnRH-a) plus tibolone in the treatment of severe premenstrual syndrome (PMS). DESIGN Prospective, double-blind, placebo-controlled clinical trial. SETTING Department of Obstetrics and Gynecology, University of Naples Federico II, Naples, Italy. PATIENT(S); Thirty patients affected by severe PMS, aged 23-29 years (mean age +/- SD, 25.3 +/- 2.9 years). INTERVENTION(S) Treatment for two cycles with leuprolide acetate depot (3.75 mg IM for 28 days) in association with tibolone (2.5 mg/d orally) or placebo (1 tablet per day orally). MAIN OUTCOME MEASURE(S) The mean severity of each symptom and sign of PMS was evaluated using a visual analog scale during the last 7 days of each treatment cycle in comparison with the last 7 days of the cycle before treatment. RESULT(S) Mean scores for each of the adverse psychological/physical and positive psychological symptoms were significantly improved during treatment. No statistically significant difference was detected between patients treated with tibolone and placebo. A significantly lower number of hot flushes per day was observed in groups treated with GnRH-a and tibolone in comparison with GnRH-a and placebo. CONCLUSION(S) Tibolone administered in association with GnRH-a does not reduce the therapeutic effect of GnRH-a in women affected by PMS. Tibolone used in association with GnRH-a may provide long-term medical treatment for women with PMS.

Menstrual status and serum leptin levels in anorectic and in menstruating women with low body mass indexes.

OBJECTIVE To evaluate serum leptin levels in anorectic women, menstruating women with low body mass indexes (BMI) and normally menstruating women with normal BMI. DESIGN Prospective study. SETTING University clinics. PATIENT(S) Fourteen amenorrheic patients with anorexia nervosa (group A), 11 menstruating women with a BMI <18 kg/m(2) (group B), and 20 normal controls. MAIN OUTCOME MEASURE(S) Determination of BMI, caloric intake, total fat mass, ovarian volume, and serum leptin, insulin-like growth factor I, FSH, LH, E(2), PRL, and TSH levels. INTERVENTION(S) None. RESULT(S) Mean BMI and fat mass were similar in groups A and B and significantly higher in controls. Mean caloric intake was significantly lower in group A than in group B and controls. Median serum leptin levels were significantly lower in group A than in group B and controls, and significantly lower in group B than in controls. Median serum insulin-like growth factor I levels were significantly lower in group A than in group B and controls. Binary segmentation analysis of groups A and B showed that LH was the most relevant variable in differentiating the two groups, followed by leptin. CONCLUSION(S) A threshold of leptin levels exist above which, even in the presence of low body mass indexes, the menstrual function is preserved.

Effectiveness of short-term administration of tibolone plus gonadotropin-releasing hormone analogue on the surgical outcome of laparoscopic myomectomy.

OBJECTIVE To evaluate whether administration of tibolone changes the effectiveness of GnRH analogue administered before laparoscopic myomectomy. DESIGN Prospective, randomized, open, placebo-controlled clinical trial. SETTING Department of Gynecology and Obstetrics, University of Naples Federico II, Naples, Italy. PATIENT(S) 66 women with symptomatic uterine leiomyomas. INTERVENTION(S) Treatment for 2 months with leuprolide acetate and iron tablets, plus tibolone (group A) or placebo tablets (group B); or with leuprolide acetate and iron tablets (group C). MAIN OUTCOME MEASURE(S) Laparoscopic myomectomy at the end of treatment. Operative time and blood loss during surgery were recorded. Uterine volume, volume and number of uterine leiomyomas, volume and echogenicity of the largest uterine leiomyomas, hematologic data, and myoma-related symptoms were evaluated at baseline and 1 week before and after surgery. RESULT(S) Uterine and leiomyomata volume and myoma-related symptoms were significantly reduced and hematologic variables improved significantly in groups A and B, compared with baseline values and with group C. Operative time and blood loss were significantly less in groups A and B than in group C. After surgery, hematologic variables were significantly worse in group C compared with groups A and B. During the study no significant difference was detected between groups A and B. CONCLUSIONS Administration of tibolone administration in patients treated with GnRH analogue before laparoscopic myomectomy does not change the effectiveness of the analogue administered alone.

Effects of estrogen-progestin therapy on serum levels of RANKL, osteoprotegerin, osteocalcin, leptin, and ghrelin in postmenopausal women.

Objective: The aim of this study was to evaluate the effects of estrogen-progestin therapy on serum levels of receptor-activating nuclear factor &kgr;&bgr; ligand (RANKL), osteoprotegerin, osteocalcin, leptin, and ghrelin in a cross-sectional study of 99 healthy postmenopausal women conducted at the Menopause Clinic of our department. Design: In this cross-sectional, observational study, 99 participants were divided into two groups. Group A was composed of 77 postmenopausal women who had never received estrogen-progestin therapy, and group B was composed of 22 postmenopausal women who had received transdermal 17&bgr;-estradiol at a dose of 50 &mgr;g/day in a continuous regimen for at least 24 months and nomegestrol at a dose of 5 mg/day for 12 days/month in a sequential regimen. All participants underwent blood sampling in the morning and quantitative ultrasound bone-densitometry measurement of the proximal phalanges of the dominant hand. Results: T score and amplitude-dependent speed of sound were significantly higher in group B than in group A. No significant differences in RANKL, osteoprotegerin, and osteocalcin were observed between the two groups. Serum leptin levels were significantly lower in group B than in group A, whereas ghrelin was significantly higher in group B than in group A. Conclusions: The data gathered in this preliminary study indicate that estrogen-progestin therapy may protect against postmenopausal bone loss, but this protective effect does not seem to be exerted through action on the RANK-RANKL-osteoprotegerin system. Similarly, although several reports suggest that leptin and ghrelin are involved in bone metabolism, we could not detect any important correlation of these two hormones with bone metabolism or bone status in treated and untreated postmenopausal women. Because of the limited number of treated participants and the study design, the results of this preliminary study must be confirmed in larger, prospective, longitudinal studies.

Effects of the contraceptive patch and the vaginal ring on bone metabolism and bone mineral density: a prospective, controlled, randomized study

BACKGROUND This study was conducted to compare the effects of the combined contraceptive vaginal ring releasing 15 mcg of ethinylestradiol (EE) and 120 mcg of etonorgestrel daily with the effects of the contraceptive patch, a transdermal system that delivers a daily dose of 20 mcg of EE and 150 mcg of norelgestromin on bone turnover and bone mineral density (BMD) in young fertile women. STUDY DESIGN On the basis of a randomized, computer-generated list, 40 women desiring contraception were assigned to a 12-month treatment with a patch delivering a daily dose of 20 mcg of EE and 150 mcg of norelgestromin (Evra, Janssen-Cilag, Italy) (Group A, n=20) or to a 12-month treatment with a vaginal ring releasing a daily dose of 15 mcg of EE and 120 mcg of etonorgestrel (NuvaRing, Organon, Italy) (Group B, n=20). Twenty patients underwent no treatment and were used as healthy controls (Group C, n=20). At 3, 6, 9 and 12 months, serum and urinary calcium, osteocalcin and urinary pyridinoline (PYD) and deoxypyridinoline (D-PYD) levels were measured. At baseline and after 12 months, lumbar BMD was determined by dual-energy X-ray absorptiometry. RESULTS In Groups A and B, urinary PYD and D-PYD at 6, 9 and 12 months were significantly reduced in comparison with basal values and Group C values (p<.05). In Groups A and B, serum calcium levels were significantly increased after 6 months. No significant difference was detected between Group A and Group B in urinary levels of PYD and D-PYD, in calcium levels and in osteocalcin levels. At 12 months, no significant difference was detected in spinal BMD values between the three groups and in comparison with basal values. CONCLUSION Both contraceptive systems exert a similar positive influence on bone turnover in young postadolescent women.