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Biomedical subjects

P Albertazzi

Publications and source records attributed to P Albertazzi.

14 recordsLinked to original sources

Oestrogen and selective oestrogen receptor modulators (SERMs): current roles in the prevention and treatment of osteoporosis.

Post-menopausal oestrogen replacement therapy (HRT) is the agent of choice for restraint of post-menopausal bone loss. In numerous observational, and in a few intervention studies, it has been shown to reduce osteoporotic fractures. However, in order to be effective treatment has to be carried on long term. This is a task not easily achieved due to poor patient adherence. The majority of patients stop treatment after a few months. Fear of breast cancer and refusal to tolerate resumption of cyclic withdrawal bleeding are the principal objections. Newer and more user-friendly forms of treatment are needed. Ideally, these should have an efficacy similar to oestrogen on the central nervous system, cardiovascular system and bone, without adverse effects on the breast and uterus. With this in mind, Selective oestrogen Receptor Modulators (SERMs) have been developed. In this chapter we review how effective modern pharmacology has been in achieving an improved design of hormonal replacement for the post-menopausal women, and the place that it has obtained today alongside both older and newer forms of treatment.

Estrogen Replacement Therapy↗

Exploration of cyclical changes in memory and mood in postmenopausal women taking sequential combined oestrogen and progestogen preparations.

OBJECTIVE: To investigate the effect of progesterone on cognitive function, mood, sleep quality and libido when added to oestrogen in sequential combined hormonal replacement therapy regimens. DESIGN: Observational study over three hormonal replacement therapy cycles. SETTING: Menopause Centre of Ospedale Maternità, Bologna, Italy. POPULATION: Twenty-three postmenopausal women with an average of 70 months of amenorrhoea (range 12 to 234 months) on different sequential combined hormonal replacement therapy regimen for an average of 15 months (range 3-48) months. METHODS: Psychological testing for memory, mood, sleep quality and libido during the oestrogen only part of the cycle compared with the oestrogen-progestogen part of the cycle. RESULTS: Twenty women completed the six visits of the trial. The addition of progestogens to oestrogen appeared to benefit memory (P < 0.01) but worsened mood (P < 0.005). There was no evidence of change in other parameters such as sleep quality or libido. CONCLUSION: The addition of progestogens improved memory above what was obtained with oestrogen alone. This effect did not depend on an improvement of mood since the latter worsened during the progestogenic phase of an hormonal replacement therapy cycle. Progestogen added to oestrogen did not significantly influence sleep or libido.

Affect↗

The life and times of the estrogen receptors: an interim report.

The estrogens profoundly influence the growth, differentiation and function of the organs of the reproductive system such as the breast, uterus and ovary, but also have an effect on the non-reproductive tissues of the skeletal, cardiovascular and central nervous systems. Formerly, only one estrogen receptor (ER) was thought to mediate all functions. Now termed ER alpha, this agent was known to reside in the nucleus, to be activated by ligand and to direct the expression of target genes. A second oestrogen receptor (ER beta) has been identified, and estrogen influence has been further clarified through demonstration of actions which operate via membrane receptors and non-genomic pathways. This review summarizes our growing understanding of receptor structure, mechanism of action and tissue distribution, together with the implication of these data for the development and clinical delivery of estrogen replacement regimens.

Drug Delivery Systems↗

The effect of tibolone versus continuous combined norethisterone acetate and oestradiol on memory, libido and mood of postmenopausal women: a pilot study.

OBJECTIVE: Several studies have shown a positive effect of oestrogen on memory, mood and well-being but these data are controversial and focus particularly on the effect of oestrogen alone. In this pilot study we have investigated the effect of a continuous combination of norethisterone acetate 1 mg and oestradiol valerate 2 mg (Kliogest) versus tibolone (Livial) on memory, sexuality and mood. METHODS: Twenty-two postmenopausal women, age range 51-57, were randomised to a 6 months single blind interventional study treatment with either continuous combined oestradiol plus norethisterone acetate, or tibolone. Computerised psychological test of memory, mood and libido were administered both before and at the end of the 6 months treatment. RESULTS: Fourteen patients completed the study; eight on Livial and six on Kliogest. Recognition memory was improved by Kliogest but not by Livial (P<0.05) while either drug equally improved both the reaction time (P<0.01) and accuracy of performance (P<0.001) of categorical semantic memory. Both the treatments improved libido significantly (P<0.05), while the mood did not change with either. CONCLUSION: The results suggest that both these forms of hormonal replacement therapy improve the efficiency of memory performance and libido. However, a combination of oestradiol and norethisterone acetate seems to be marginally more effective on improving cognitive processes.

Affect↗

Pyoderma gangrenosum of the cervix.

BACKGROUND: Ulcerated cervical lesions are common findings in gynecology, but pyoderma gangrenosum presenting solely as a cervical ulcer is unusual. CASE: A 33-year-old nulligravida presented with postcoital bleeding and an extensive ulcerated lesion of the cervix that showed nonspecific inflammation on biopsy. After 6 months of topical steroid treatment, the lesion resolved completely. CONCLUSION: Pyoderma gangrenosum should be suspected in nonspecific cervical ulcers, especially those that worsen after surgical resection or ablation and then respond to steroid treatment.

Adult↗

Plasma lipoproteins in soy-treated postmenopausal women: a double-blind, placebo-controlled trial.

BACKGROUND AND AIM: Postmenopausal modification of the lipid profile plays a major role in the risk of ischemic heart disease. Lifestyle counseling and estrogen replacement therapy have all been proposed as first-line measures, but there is no agreement on the best way to treat climacteric dyslipidemia. Soybean-based diet seems particularly attractive in this context, given its cholesterol lowering potential, its hypothetical anticancerous effects and possible modification of climacteric symptoms. METHODS AND RESULTS: We evaluated the effect of 60 g isolated soy protein (ISP) daily on the lipid profile of 104 postmenopausal women (53.3 +/- 3.3 years) in a double-blind, parallel, placebo-controlled (caseinate) trial, as part of a broader assessment of the effect of ISP on climacteric symptomatology. Serum total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides, apo A-I, apo B and lipoprotein (a) were determined before and after a 12-week diet modification. Seventy-seven women completed the trial. Both soy and placebo determined a significant reduction in total cholesterol (-0.42 +/- 0.79 and -0.40 +/- 0.57 mmol/L) and LDL-cholesterol (-0.35 +/- 0.72 and -0.31 +/- 0.54 mmol/L), but only soy had a significant lowering effect on apo B and the LDL-cholesterol/HDL-cholesterol ratio (-6% and -8% from baseline respectively); lipoprotein (a) plasma levels were not significantly changed by either treatment. Forty-four women were dyslipidemic at baseline; those with increased LDL concentrations showed a somewhat greater improvement in their lipoprotein profile (LDL-cholesterol and apo B reduction) with soy rather than placebo. No further information emerged when the subjects were divided into three apo E phenotypes. CONCLUSIONS: We conclude that diet supplementation with 60 g ISP is slightly better than caseinate in favorably modifying the lipoprotein metabolism of postmenopausal women; this effect is more evident in hypercholesterolemic subjects.

Caseins↗

Dietary soy supplementation and phytoestrogen levels.

OBJECTIVE: To investigate the relationship between levels of phytoestrogens in blood and urine and symptom control in postmenopausal women whose diets were supplemented with soy containing high levels of phytoestrogen. METHODS: Phytoestrogen levels in blood and urine were correlated with the number of hot flushes and vaginal maturation indices in 104 postmenopausal women whose diets were supplemented with 60 g of soy powder daily for 3 months in a double-masked, parallel, placebo-controlled trial. The effect of soy supplementation on menopausal symptoms in this study population was reported previously. RESULTS: Serum levels of genistin, daidzin, and equol were significantly higher in women after soy diet supplementation (+756%, +593%, +1008%, and 57% respectively). The concentration of enterolactone in the soy group was increased by 57% compared with baseline, but the difference with placebo was not statistically significant. The increase in phytoestrogen levels in the soy group in blood or urine did not correlate with fewer hot flushes. Vaginal maturation indices did not change in the soy group. CONCLUSION: Phytoestrogen levels increased in women who consumed soy supplement, but that does not fully explain climacteric symptom reduction. It is possible that other types of yet unknown phytoestrogens or components in soy other than phytoestrogen influence hot flushes.

Climacteric↗

Tibolone: a review.

Tibolone appears to be at least as efficacious as other forms of hormonal replacement therapy (HRT) on climacteric symptoms. It does not cause withdrawal bleeding when used in women with at least 1 year of amenorrhea. It is, therefore, not indicated in perimenopause because it may cause irregular bleeding. The androgenic action of tibolone may have a two-fold benefit: on the one hand, it may help depression and libido more than other forms of HRT, while, on the other hand, it may improve some lipid parameters such as Lp(a), and triglycerides. However, this androgenic action, may also be responsible for the reduction of HDL cholesterol, that may thus reduce the beneficial effect of tibolone on lipids. It is estimated that only 30% of cardiovascular risk protection of HRT is due to improvement of classical lipids parameters while a great role is played by the direct effect of estrogen on vessels. Tibolone, as well as estrogen, has been shown to induce peripheral vasodilatation and also has a direct effect on vascular reactivity thus increasing peripheral blood flow with no changes in blood pressure or cardiac output. Tibolone seems to exert a similar effect as other forms of HRT on markers of bone metabolism and bone mass, but no data is yet available on fracture prevention.

Anabolic Agents↗

The effect of dietary soy supplementation on hot flushes.

OBJECTIVE: To assess the effect of daily dietary supplementation of soy protein isolate powder on hot flushes in postmenopausal women. METHODS: We carried out a double-blind, parallel, multicenter, randomized placebo-controlled trial of 104 postmenopausal women. Fifty-one patients (age range 48-61 years) took 60 g of products containing 40 g of isolated soy protein [corrected] daily and 53 patients (age range 45-62 years) took 60 g of placebo (casein) daily. The study lasted 12 weeks. Using analysis of covariance, we analyzed changes from baseline in mean number of moderate to severe hot flushes (including night sweats) during treatment. RESULTS: Soy was significantly superior to placebo (P < .01 in reducing the mean number of hot flushes per 24 hours after 4, 8, and 12 weeks of treatment. In particular, women taking soy had a 26% reduction in the mean number of hot flushes by week 3 and a 33% reduction by week 4 (P < .001 by the Wilcoxon exact test). By the end of the 12th week, patients taking soy had a 45% reduction in their daily hot flushes versus a 30% reduction obtained with the placebo (P < .01). The overall rates of adverse effects were similar for soy and casein-placebo. Twenty-five patients dropped out of the study: 11 in the soy group and 14 in the placebo group. Gastrointestinal side effects were the most common cause of premature withdrawal from the study (seven patients in each group). CONCLUSION: Soy protein isolate added daily to the diet substantially reduced the frequency of hot flushes in climacteric women.

Cohort Studies↗

Sequential addition of low dose of medrogestone or medroxyprogesterone acetate to transdermal estradiol: a pilot study on their influence on the endometrium.

We evaluated bleeding pattern and endometrium following the administration of two of the most common types of progestogens used in hormone replacement therapy, medroxyprogesterone acetate (MPA) and medrogestone acetate. Twenty eight patients in spontaneous menopause were randomly allocated to two groups. Group 1 (n = 14) received 5 mg/day of of MPA and group 2 (n = 14) received 5 mg/day of medrogestone: both the progestogens were sequentially added for the last 12 days of a 21-day period of transdermal estradiol administration (50 micrograms per day). A 7-day treatment-free period completed the cycle. The study treatments were administered for 6 cycles. The endomtria were checked for their thickness by transvaginal ultrasound before starting treatment and at 6th treatment cycle (days 6-10 of the estrogen-only phase and during the period between days 8 and 12 of the progestogen addition). Endometrial biopsies were performed before starting treatment only in the patients with a positive progesterone challenge test and in all the patients at the end of the study during the addition of the progestogen. The bleeding pattern was closely monitored. MPA is accompanied by a thick endometrium with full secretory transformation in all cases. On the contrary, the same dose of medrogestone induced a consistent decrease of estrogen primed endometrium with only 4 cases of full secretory transformation. Four medrogestone-treated patients dropped out due to unscheduled bleeding. A low dose of medrogestone added to transdermal estradiol induced incomplete transformation of endometrium and oligo-amenorrhea more frequently than MPA, but it increased the chances of irregular bleeding. MPA fully transformed the endometrium: periods were thus heavier but regular. None of the patients in either group had endometrial hyperplasia.

Administration, Cutaneous↗

Trazodone: a non-hormonal alternative for neurovegetative climacteric symptoms.

Hormone replacement therapy (HRT) is the treatment of choice for neurovegetative climacteric symptoms. In some women, however, HRT may either be contraindicated, or the patients themselves may prefer a non-hormonal form of treatment. Trazodone is a drug that acts a weak, but specific, inhibitor of the uptake of 3H-serotonin and is generally used for its antidepressant effects. In this study we have observed the efficacy of oral Trazodone (75 mg/day) in the treatment of the climacteric symptoms in 25 menopausal patients recruited at the Menopause Clinic of Ferrara University Hospital. The symptoms were scored from 0 to 3 according to presence and intensity. The patients were all complaining of climacteric neurovegetative symptoms (average symptom score 2.43). Symptoms scores were recorded before starting treatment and then again after 3 months. The appeared to be particularly effective on the intensity of anxiety (OR: 0.08, CI: 0-0.080), insomnia (OR: 0.15, CI: 0.02-0.71), and irritability (OR: 0.29, CI: 0.04-1.48). The intensity of hot flushes appeared reduced but was not statistically significant (OR: 0.52, CI: 0.08-1.87). However, the average total score of symptoms appearing in the Kupperman scale was reduced (-14%) after treatment. Trazodone should be kept in mind as a possible alternative to HRT. This drug can be particularly useful for those patients whose climacteric symptoms have a marked connotation of anxiety rather than for hot flushes or when HRT are contraindicated.

Anti-Anxiety Agents↗

The menopausal transition: a dynamic approach to the pathogenesis of neurovegetative complaints.

In our cross-sectional study we investigated the separate influence of three main factors, namely menopausal and estrogen status, and chronological age, on ten neurovegetative climacteric complaints reported in the scale of Kupperman et al. A multivariate statistical analysis was performed by a multivariate statistical approach on 1161 untreated women seen at the Menopause Center of the Ferrara University Hospital. Ninety women (age range, 41-54 years) were premenopausal; 492 women (age range, 38-55 years) were perimenopausal with irregular periods or amenorrhea for less than 12 months; 468 women (age range, 41-69 years) had a spontaneous menopause (age range, 37-66 years); 111 had had hysterectomy with bilateral ovariectomy while still regularly menstruating. Serum estrone was used as the indicator of the patients' estrogen status. A clear positive trend was demonstrated between menopausal status and the prevalence of depression, hot flushes, insomnia and joint pain. However, only the prevalence of hot flushes amongst these four symptoms was significantly related with the climacteric estrogen decline (beta = -0.006, P = 0.001). Moreover, menopausal status appeared to influence the intensity of fatigue, hot flushes, insomnia and paresthesia. Age was found to significantly (P = 0.053) co-vary only with the intensity of the hot flushes, with a positive relation (beta = 0.092, r = 0.104, P = 0.003), whereas estrone values did not significantly co-vary with any symptom. Furthermore, while neurovegetative symptoms are largely present also in the absence of hot flushes, when these latter are present, they exacerbate both the intensity and the prevalence of all the other symptoms.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗