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Biomedical subjects

Andrea Riccardo Genazzani

Publications and source records attributed to Andrea Riccardo Genazzani.

At least 19 recordsLinked to original sources
PubMed2006

Estrogen, cognition and female ageing.

Starting from fetal life, estrogens are crucial in determining central gender dimorphism, and an estrogen-induced synaptic plasticity is well evident during puberty and seasonal changes as well as during the ovarian cycle. Estrogens act on the central nervous system (CNS) both through genomic mechanisms, modulating synthesis, release and metabolism of neurotransmitters, neuropeptides and neurosteroids, and through non-genomic mechanisms, influencing electrical excitability, synaptic function and morphological features. Therefore, estrogen's neuroactive effects are multifaceted and encompass a system that ranges from the chemical to the biochemical to the genomic mechanisms, protecting against a wide range of neurotoxic insults. Clinical evidences show that, during the climacteric period, estrogen withdrawal in the limbic system gives rise to modifications in mood, behaviour and cognition and that estrogen administration is able to improve mood and cognitive efficiency in post-menopause. Many biological mechanisms support the hypothesis that estrogens might protect against Alzheimer's disease (AD) by influencing neurotransmission, increasing cerebral blood flow, modulating growth proteins associated with axonal elongation and blunting the neurotoxic effects of beta-amyloid. On the contrary, clinical studies of estrogen replacement therapy (ERT) and cognitive function have reported controversial results, indicating a lack of efficacy of estrogens on cognition in post-menopausal women aged >or=65 years. These findings suggest the presence of a critical period for HRT-related neuroprotection and underlie the potential importance of early initiation of therapy for cognitive benefit. In this review, we shall first describe the multiple effects of steroids in the nervous system, which may be significant in the ageing process. A critical update of HRT use in women and a discussion of possible prospectives for steroid use are subsequently proposed.

Aging↗
PubMed2006

Old and new perspectives in the management of high-risk, locally advanced or recurrent, and metastatic vulvar cancer.

During the last decades there has been a continuing evolution in the surgical approach of squamous cell carcinoma of the vulva that has been traditionally treated with radical vulvectomy and bilateral inguinal-femoral lymphadenectomy. Patients with T1 tumour are usually treated with radical local excision, if the lesion is unifocal and the remainder of the vulva is normal. Patients with T1a disease have no risk of groin metastases and do not need lymphadenectomy, whereas those with T1b disease need ipsilateral inguinal-femoral lymphadenectomy if the lesion is lateral, and bilateral lymphadenectomy if the lesion is midline. Modifications of the surgical technique of deep femoral lymphadenectomy and the mapping of sentinel node can offer new interesting therapeutic perspectives. Postoperative adjuvant pelvic and groin irradiation is warranted for patients with two or more or macroscopically involved groin nodes. Locally advanced squamous cell carcinoma of the vulva has been long surgically treated with en-block radical vulvectomy and bilateral inguinal-femoral lymphadenectomy plus partial resection of urethra, vagina or anum, or by exenteration, with severe postsurgical complications, poor quality of life, and unsatisfactory survival rates. 5-Fluorouracil [5-FU] or 5-FU- and cisplatin-based chemotherapy concurrent with irradiation followed by tailored surgery represents an attractive therapeutic option for advanced disease, planned to avoid such ultra-radical surgical procedures and, hopefully, to improve patient outcome. Chemotherapy has also been used in neoadjuvant setting, with contrasting and generally unsatisfactory results, and in palliative treatment of patients with distant metastases. Surgery is the primary treatment also for vulvar malignancies other than squamous cell carcinoma, whereas the clinical usefulness of adjuvant irradiation or chemotherapy is still to be defined. Primary chemoradiation can be also used for advanced carcinoma of the Bartholin gland or for advanced adenocarcinoma associated with extramammary Paget's disease. The drugs used for chemotherapy of metastatic melanomas or sarcomas of the vulva are the same employed for the melanomas or sarcomas developed in other sites.

Combined Modality Therapy↗
PubMed2006

Progesterone and medroxyprogesterone acetate effects on central and peripheral allopregnanolone and beta-endorphin levels.

The increased use of hormonal therapies has led to the study of the properties of different progestin molecules and their effects on the central nervous system. The central and peripheral levels of neurosteroid allopregnanolone and the opioid peptide beta-endorphin (beta-END) are regulated by estrogens. The aim of the present study was to investigate the effects of a 2-week oral treatment with micronized progesterone or medroxyprogesterone acetate (MPA) alone or in addition to estradiol valerate (E2V) on central and peripheral allopregnanolone and beta-END levels in ovariectomized (OVX) female rats. Thirteen groups of Wistar OVX rats received one of the following treatments: oral progesterone (2, 4 or 8 mg/kg/day); oral MPA (0.05, 0.1 or 0.2 mg/kg/day); E2V (0.05 mg/kg/day); E2V + progesterone (0.05 mg/kg/day + 2, 4 or 8 mg/kg/day), or E2V + MPA (0.05 mg/kg/day + 0.05, 0.1 or 0.2 mg/kg/day) for 14 days. One group of fertile and one group of OVX rats were used as controls. The concentration of allopregnanolone was assessed in the frontal and parietal lobes, hypothalamus, hippocampus, anterior pituitary, adrenals and serum, while the beta-END content was assessed in the frontal and parietal lobes, hypothalamus, hippocampus, anterior and neurointermediate pituitary, and plasma. E2V administration reverted the ovariectomy-induced reduction in allopregnanolone and beta-END. Progesterone and MPA increased allopregnanolone levels in all tissues except in the adrenal gland. The combined administration of progesterone or MPA and E2V determined a further increase in allopregnanolone levels with respect to E2V alone except in the adrenal gland and hippocampus only after MPA treatment. Progesterone did not affect beta-END levels in the frontal and parietal lobes, hippocampus and anterior pituitary, while it caused an increase plasma, hypothalamic and neurointermediate pituitary beta-END levels. MPA only affected beta-END levels in the hippocampus and in the neurointermediate lobe. The combined administration of progesterone or MPA and E2V did not alter the effect of estradiol or it determined a further dose-dependent increase in beta-END levels. In conclusion, this study demonstrates that progesterone and MPA have a similar but not identical effect on central and peripheral allopregnanolone and beta-END levels. Their association with an estrogenic compound does not interfere with the positive effects produced by estrogen on allopregnanolone and beta-END brain content.

Administration, Oral↗
PubMed2006

Old and new perspectives in the pharmacological treatment of advanced or recurrent endometrial cancer: Hormonal therapy, chemotherapy and molecularly targeted therapies.

Hormonal therapy and chemotherapy play a major role in the management of advanced or recurrent endometrial cancer. Progesterone therapy obtains overall response rates ranging from 11% to 25% in patients with endometrioid-type tumours, and oral medroxyprogesterone acetate 200mg daily appears to be a reasonable therapeutic option for those lesions that are well differentiated and/or have a high progesterone receptor (PgR) content. However, the activity of progestins is often compromised by the down-regulation of PgR within the target tissues, and therefore therapeutic strategies designed to enhance PgR expression are warranted. Little data are currently available about the new aromatase inhibitors and selective estrogen receptor modulators. As for chemotherapy, the combination of doxorubicin [DOX]+cisplatin [CDDP] achieves overall response rates ranging from 34% to 60%, and the addition of paclitaxel (TAX) seems to improve response rates, progression-free survival and overall survival, but to worsen toxicity profile. A phase III study is currently comparing TAX+DOX+CDDP versus the less toxic combination of TAX+carboplatin. Chemotherapy is active against both endometrioid-type carcinoma and uterine serous papillary carcinoma. However, this latter endometrial malignancy is less chemosensitive than the histologically similar high-grade serous ovarian carcinoma. Interesting fields of research are represented by investigational agents directed against specific intracellular signal transduction pathways involved in the proliferation, invasiveness and metastatic spread of endometrial cancer. Mammalian target of the rapamycin (mTOR) inhibitors, epidermal growth factor receptor inhibitors (gefitinib, erlotinib, lapatinib, the monoclonal antibody cetuximab), imatinib, the monoclonal antibody trastuzumab, and the Clostridium perfrigens enterotoxin are currently under evaluation as molecularly targeted therapies for endometrial cancer. Further investigations addressed to better understand the signal transduction pathways that are disregulated in endometrial carcinogenesis could identify novel biological targets suitable for tailored therapies.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2006

Effect of raloxifene on cardiovascular adverse events in postmenopausal women with osteoporosis.

The impact of selective estrogen receptor modulators on cardiovascular disease outcomes in postmenopausal women remains unclear. This analysis assessed the effect of raloxifene on the incidence of cardiovascular adverse events in postmenopausal women followed for < or =8 years as participants in a 4-year osteoporosis treatment trial and a subsequent 4-year follow-up trial. The Continuing Outcomes Relevant to Evista (CORE) trial, designed to determine the effect of raloxifene on the incidence of invasive breast cancer, was a 4-year follow-up study to the 4-year Multiple Outcomes of Raloxifene Evaluation (MORE) osteoporosis treatment trial. Of the 7,705 participants originally enrolled in MORE, 4,011 were enrolled in CORE and thus participated in both trials (MORE-CORE participants). The incidence of serious cardiovascular (i.e., coronary and cerebrovascular) adverse events during 8 years, confirmed by external adjudication in the 2 trials, was compared between treatment groups using Cox proportional hazards models. The 8-year incidence of serious cardiovascular adverse events did not differ significantly between the raloxifene (5.5%) and placebo (4.7%) groups (hazard ratio [HR] 1.16, 95% confidence interval [CI] 0.86 to 1.56). Similar results were obtained when coronary (HR 1.22, 95% CI 0.82 to 1.83) or cerebrovascular (HR 1.19, 95% CI 0.78 to 1.84) events were analyzed separately, and when cardiovascular events were analyzed in the 459 MORE-CORE participants who were at increased risk of cardiovascular events by previously established criteria (HR 1.03, 95% CI 0.58 to 1.82). In conclusion, we found no evidence of a beneficial or harmful effect of raloxifene on the incidence of cardiovascular events overall, or coronary or cerebrovascular events, in postmenopausal osteoporotic women at relatively low risk of cardiovascular events.

Aged↗
PubMed2006

Effect of climacteric transition and hormone replacement therapy on body weight and body fat distribution.

In the present study we evaluated the effects of climacteric modifications on body weight and fat distribution. From women attending a menopause clinic we selected 2175 untreated, normal healthy women who were divided into three groups: premenopausal (n = 540), perimenopausal (n = 750) and postmenopausal (n = 885), and compared them with 354 postmenopausal women receiving different forms of hormone replacement therapy (HRT). The total body fat tissue mass and distribution were analyzed using dual-energy X-ray absorptiometry. Body weight and body mass index (BMI) were significantly higher in perimenopausal and postmenopausal than in premenopausal women. Mean total body fat and fat as a percentage of soft tissue were significantly (p < 0.05) higher in the perimenopausal and postmenopausal groups than in the premenopausal group. Fat tissue and regional fat tissue as a percentage of total fat tissue were higher in the trunk (p < 0.0001) and arms (p < 0.0001) in perimenopausal and postmenopausal than in premenopausal women. In postmenopausal women, leg fat tissue was significantly (p < 0.05) lower than in premenopausal and perimenopausal groups. Total body and leg lean tissue were significantly lower (p < 0.05) in postmenopausal than in premenopausal and perimenopausal women. In age-matched women with similar BMI, total body fat as a percentage of soft tissue was significantly (p < 0.001) higher in the perimenopausal and postmenopausal groups than in the premenopausal group. As for body fat distribution, fat as a percentage of total fat tissue was significantly higher in the trunk (p < 0.0001) region in perimenopausal and postmenopausal women compared with the premenopausal group. In the legs, fat as a percentage of total fat tissue was significantly higher (p < 0.05) in the premenopausal than in the postmenopausal group. In the arms a slight but not significant (p < 0.18) difference was shown in fat distribution between the three untreated groups. In age-matched HRT-treated postmenopausal women, the fat tissue was similar to that in the premenopausal group. The present results confirm that endocrine changes during the menopausal transition, rather than the aging process, are related to changes in body weight and fat distribution. Perimenopausal and postmenopausal women show a shift to a central, android fat distribution that can be counteracted by HRT.

Adult↗
PubMed2006

Vascular endothelial growth factor and basic fibroblast growth factor in polycystic ovary syndrome during controlled ovarian hyperstimulation.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a common endocrine disorder that causes anovulation and consequent subfertility. It is well established that increased ovarian mass, supported by new blood vessel proliferation in stroma and theca, is a key feature of PCOS. Recent studies suggest a role for angiogenetic factors in this phenomenon. AIM: To evaluate of levels of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in serum and follicular fluid of PCOS patients during a controlled ovarian hyperstimulation. METHODS: In 52 patients undergoing in vitro fertilization treatments, 26 PCOS patients and 26 controls, serum VEGF and bFGF levels were assessed before starting administration of follicle-stimulating hormone (FSH) (day 0), on the day of administration of human chorionic gonadotropin (hCG) and on the day of oocyte retrieval. Follicular fluid levels of the two growth factors were detected on the day of oocyte retrieval. RESULTS: PCOS patients showed higher serum VEGF levels than controls before starting FSH administration, on the day of hCG administration and on the day of oocyte retrieval. Serum VEGF levels showed a rise after hCG administration only in the PCOS patients. In addition, serum bFGF levels were higher in PCOS patients than in controls on the day of hCG administration and the day of oocyte retrieval. Furthermore, on the day of hCG administration, serum bFGF levels were directly correlated to the amount of FSH previously administered (p < 0.0001). In follicular fluid, higher VEGF and bFGF levels were found in PCOS patients than in controls. Furthermore, follicular-fluid bFGF concentrations were inversely correlated with the percentage of mature oocytes collected (p < 0.05). CONCLUSIONS: The present study revealed elevated levels of VEGF and bFGF in serum and follicular fluid in PCOS patients compared with controls. bFGF seems to be an FSH-dependent growth factor and its levels in follicular fluid are inversely correlated with the percentage of mature oocytes collected.

Case-Control Studies↗
PubMed2006

Activation of nitric oxide synthesis in human endothelial cells using nomegestrol acetate.

OBJECTIVE: Recent clinical trials indicate that synthetic progestins may be unexpectedly relevant for the development of cardiovascular disease. The aim of this study was to establish whether nomegestrol acetate induces signaling events in human endothelial cells that differ from those of other progestins, such as natural progesterone or medroxyprogesterone acetate. METHODS: We used human endothelial cells to study the action of nomegestrol acetate (either alone or in the presence of estradiol [E2]) on the synthesis of nitric oxide (NO) and on the activity or expression of endothelial nitric oxide synthase (eNOS). We compared the effects of nomegestrol acetate with those of progesterone or medroxyprogesterone acetate. In addition, we characterized the signaling events recruited by these compounds. RESULTS: Progesterone and nomegestrol acetate increase NO synthesis by transcriptional and nontranscriptional mechanisms, whereas medroxyprogesterone acetate lacks such effects. When used together with physiological E2 concentrations, progesterone and nomegestrol acetate do not interfere with (or even enhance) E2 effects, whereas medroxyprogesterone acetate impairs E2 signaling. A marked difference in the recruitment of mitogen-activated protein kinase and phosphatidylinositol-3 kinase explains the divergent effects of the three gestagens. CONCLUSION: Our findings show significant differences in the signal transduction pathways recruited by progesterone, nomegestrol acetate, and medroxyprogesterone acetate in human endothelial cells that may have relevant clinical implications.

Cells, Cultured↗
PubMed2005

Longitudinal evaluation of perimenopausal bone loss: effects of different low dose oral contraceptive preparations on bone mineral density.

OBJECTIVES: To evaluate the pattern of mineral density in eumenorrhoic and oligomenorrhoic perimenopausal women, and assess the effects of different low dose oral contraceptives (OC) on bone metabolism and spine bone density. METHODS: Spine bone density was evaluated in a longitudinal 2-year follow-up, randomized, unblinded, uncontrolled clinical trial conducted in healthy, normally menstruating perimenopausal women, perimenopausal oligomenorrhoic women and in perimenopausal oligomenorrhoic women treated with an oral contraceptive containing 20 microg ethinyl estradiol plus 0.15 mg desogestrel, 0.100 mg levonorgestrel, 0.75 mg of gestodene (n=15 in each group). The results were analyzed by factorial or repeated measures analysis of variance, as appropriate. RESULTS: During the observation period, in normal menstruating women there were no changes in menstrual cycle, plasma FSH and estradiol levels, and spine bone density. In oligomenorrhoic untreated women an increase in cycle length, with a concomitant decrease in plasma estradiol and an increase in plasma FSH levels were evidenced (p<0.05). In this group a significant decrease in bone density (p<0.05) occurred. In OC-treated women, a significant (p<0.05) increase in bone density was observed, with no differences among different groups. CONCLUSION: Different progestins used in OC preparations do not modify the bone sparing effect of perimenopausal OC administration avoiding the decrease in bone density.

Adult↗
PubMed2005

New evidence regarding hormone replacement therapies is urgently required transdermal postmenopausal hormone therapy differs from oral hormone therapy in risks and benefits.

Controversies about the safety of different postmenopausal hormone therapies (HTs) started 30 years ago and reached a peak in 2003 after the publication of the results from the Women Health Initiative (WHI) trial and the Million Women Study (MWS) [Writing group for the women's health initiative investigations. Risks and benefits of estrogen plus progestin in healthy postmenopausal women. JAMA 2002;288:321-33; Million women study collaborators. Breast cancer and hormone-replacement therapy in the million women study. Lancet 2003;362:419-27]. The single HT formulation used in the WHI trial for non hysterectomized women-an association of oral conjugated equine estrogens (CEE-0.625 mg/day) and a synthetic progestin, medroxyprogesterone acetate (MPA-2.5 mg/day)-increases the risks of venous thromboembolism, cardiovascular disease, stroke and breast cancer. The MWS, an observational study, showed an increased breast cancer risk in users of estrogens combined with either medroxyprogesterone acetate (MPA), norethisterone, or norgestrel. It is unclear and questionable to what extent these results might be extrapolated to other HRT regimens, that differ in their doses, compositions and administration routes, and that were not assessed in the WHI trial and the MWS. Significant results were achieved with the publication of the WHI estrogen-only arm study [Anderson GL, Limacher M, Assaf AR, et al. Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: the Women's Health Initiative randomized controlled trial. JAMA 2004;291:1701-1712] in which hormone therapy was reserved to women who had carried out hysterectomy. What emerged from this study will allow us to have some important argument to develop.

Administration, Cutaneous↗
PubMed2005

Consolidation and maintenance treatments for patients with advanced epithelial ovarian cancer in complete response after first-line chemotherapy: a review of the literature.

Most patients with advanced epithelial ovarian cancer experience objective responses to paclitaxel/platinum-based chemotherapy, but responses are generally short-lived and the clinical outcome is still unsatisfactory. Therefore, the strategy to consolidate and to prolong the duration of response is very attractive. Different consolidation or maintenance treatments have been attempted, such as whole abdomen radiotherapy, intraperitoneal chromic phosphate, radioimmunotherapy, intraperitoneal chemotherapy, high-dose chemotherapy with haematopoietic support, prolonged administration of the first-line regimen, second-line single-agent chemotherapy, and biological agents. Clinical studies have given conflicting, inconclusive, and generally disappointing results. A recent US randomised trial appeared to show that the prolonged administration of single-agent paclitaxel (175 mg/m2 every 3 weeks) significantly improved the progression-free survival of complete responders to paclitaxel/platinum-based chemotherapy. Alternative less toxic, and probably more effective schedules of administration of chemotherapy (i.e. weekly paclitaxel) might assure a better balance between quality of life and anti-tumor activity in patients previously exposed to chemotherapy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2005

Effect of dehydroepiandrosterone on central and peripheral levels of allopregnanolone and beta-endorphin.

OBJECTIVE: To evaluate the effects of dehydroepiandrosterone (DHEA) oral administration on neuroendocrine function by investigating the modulation exerted by DHEA administration on allopregnanolone and beta-endorphin (beta-EP) central and peripheral levels in ovariectomized rats. DESIGN: Prospective study. SETTING(S): Experimental research environment. ANIMAL(S): Female Wistar rats (n = 48). INTERVENTION(S): Forty rats were ovariectomized and received an oral treatment with either placebo or 0.5, 1, or 2 mg/kg/day of DHEA. After euthanization, beta-EP levels were measured in hippocampus, hypothalamus, anterior pituitary, neurointermediate pituitary, and plasma. Allopregnanolone and DHEAS levels were measured in hippocampus, hypothalamus, anterior pituitary, adrenal glands, and serum. Serum E(2) concentration was also measured. MAIN OUTCOME MEASURE(S): Dehydroepiandrosterone sulfate ester (DHEAS), E(2), beta-EP, and allopregnanolone levels. RESULT(S): Dehydroepiandrosterone administration increased DHEAS content in all organs and serum, except for anterior pituitary, where no significant changes occurred. DHEA administration in ovariectomized animals did not significantly increase E(2) circulating levels. DHEA administration induced an increase in allopregnanolone and beta-EP content in hippocampus, hypothalamus, and anterior pituitary and in serum or plasma. CONCLUSION(S): Dehydroepiandrosterone administration in ovariectomized animals increased allopregnanolone and beta-EP central and peripheral levels, which suggests that this compound may play a role as a neuroendocrine mediator, possibly substantiating the beneficial effects of postmenopausal DHEA therapy on the central nervous system.

Adjuvants, Immunologic↗
PubMed2005

Endocrinology of menopausal transition and its brain implications.

The central nervous system is one of the main target tissues for sex steroid hormones, which act on both through genomic mechanisms, modulating synthesis, release, and metabolism of many neuropeptides and neurotransmitters, and through non-genomic mechanisms, influencing electrical excitability, synaptic function, morphological features, and neuron-glia interactions. During the climacteric period, sex steroid deficiency causes many neuroendocrine changes. At the hypothalamic level, estrogen withdrawal gives rise to vasomotor symptoms, to eating behavior disorders, and altered blood pressure control. On the other hand, at the limbic level, the changes in serotoninergic, noradrenergic, and opioidergic tones contribute to the modifications in mood, behavior, and nociception. Hormone replacement therapy (HRT) positively affects climateric depression throughout a direct effect on neural activity and on the modulation of adrenergic and serotoninergic tones and may modulate the decrease in cognitive efficiency observed in climaterium. The identification of the brain as a de novo source of neurosteroids, suggests that the modifications in mood and cognitive performances occurring in postmenopausal women may also be related to a change in the levels of neurosteroids. These findings open new perspectives in the study of the effects of sex steroids on the central nervous system and on the possible use of alternative and/or auxiliary HRT.

Brain↗
PubMed2005

Polycystic ovary syndrome and gynecological cancers: is there a link?

Polycystic ovary syndrome [PCOS] is the most common endocrinopathy of women in reproductive age. An association between PCOS and type-1 endometrial cancer has often been reported in the literature. The prolonged anovulation with consequent continued secretion of estrogen unopposed by progesterone may enhance the development and growth of this malignancy, particularly in young women. Hypersecretion of luteinizing hormone [LH], chronic hyperinsulinemia and increased serum insulin-like growth factor [IGF]-I levels may represent risk factors for endometrial cancer. However, data available in the literature do not allow a meta-analysis to be carried out to calculate an estimate of the relative risk of endometrial cancer in women with PCOS. Anecdotal cases of low-grade endometrial stromal sarcoma and carcinosarcoma have been reported in association with prolonged unopposed estrogen stimulation, and in particular with PCOS. A few studies have addressed the possibility of an association between PCOS and epithelial ovarian cancer risk, and the results are conflicting but generally reassuring, and similarly the few available data appear to exclude a strong association between PCOS and breast cancer.

Breast Neoplasms↗
PubMed2005

Breast cancer and sex steroids: critical review of epidemiological, experimental and clinical investigations on etiopathogenesis, chemoprevention and endocrine treatment of breast cancer.

There is strong epidemiological, experimental and clinical evidence that the etiology of breast cancer is closely related to long-term exposure of breast epithelium to sex steroid hormones. Estrogens can enhance the development of breast cancer by stimulating cell proliferation rate and thereby increasing the number of errors occurring during DNA replication, as well as by causing DNA damage via their genotoxic metabolites produced during oxidation reactions. Anti-estrogenic drugs, including tamoxifen, raloxifene and anastrozole, have been tested with promising results in the chemoprevention of breast cancer in high-risk women. As for the use of exogenous sex-steroids in the gynecological practice, data about breast cancer risk associated with oral contraception are reassuring, and available data on oral hormone replacement therapy (HRT) use for not more than 5 years have failed to detect a significant increase in the risk of developing a breast cancer. Long-term HRT administration increases the incidence of this tumor slightly, with a relative risk ranging from 1 to 2 depending on hormone preparation. Estrogens alone, even if taken for long periods of time, seem to be safer than estrogen/progestin combinations. New administration routes and novel hormone regimens are currently under evaluation, and these new HRT modalities could have different impact on breast cancer risk because of their metabolic and pharmacodynamic effects.

Breast Neoplasms↗
PubMed2005

Therapeutic strategies for ovulation induction in infertile women with polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is a heterogeneous disorder characterized by hirsutism, obesity, hyperandrogenism and insulin resistance. The syndrome is often accompanied by infertility because of anovulation. Many approaches have been proposed to solve this problem, with the most commonly used therapies being ovarian drilling and pharmacological ovulation induction. Ovarian drilling is a procedure in which a laser fiber or electro-surgical needle punctures the ovary four to ten times. Side-effects are rare and often related to surgery itself. Pharmacological strategies include administration of metformin and insulin-sensitizing agents, clomiphene citrate (CC), gonadotropins and aromatase inhibitors. Metformin appears valuable in increasing ovulation rate, menstrual cyclicity and pregnancy rate. CC is an oral estrogen antagonist that raises circulating concentrations of follicle-stimulating hormone (FSH) and induces follicular growth in most women with PCOS and anovulation. Failure to respond is associated with high body mass index and high androgen levels. Aromatase inhibitors mimic the central reduction of negative feedback through which CC works. Ovulation induction with recombinant FSH has proved successful, but treatment requires skill and experience to avoid multiple pregnancies and ovarian hyperstimulation syndrome. The hypothetical deleterious effects of the high luteinizing hormone concentrations observed in PCOS patients seem to be related to the concomitant hyperinsulinemia (and/or insulin resistance). A thorough understanding of the syndrome and a careful assessment of each patient are the mainstays for choosing an appropriate treatment regimen.

Anovulation↗
PubMed2004

Serum tumor markers in the management of ovarian, endometrial and cervical cancer.

CA 125 is the most reliable serum marker for ovarian carcinoma. Whereas its role in the screening of the malignancy is controversial, serum CA 125 assay is very useful for both the differential diagnosis of ovarian masses, particularly in postmenopause, and the monitoring of the response to chemotherapy and follow-up of patients with histologically proven ovarian carcinoma. Tumor-associated antigens other than CA 125, such as CA 19.9, CA 15.3 and TAG.72, firstly identified in gastro-intestinal or breast malignancies, have been detected also in tissue and serum samples from patients with ovarian carcinoma. In particular CA19.9 offers the advantage of high sensitivity for mucinous histotype, which often fails to express CA 125. Serum CA 125 correlates with the clinical course of disease better than the other antigens, and in patients with positive CA 125 assay at diagnosis the concomitant evaluation of CA 19.9 or CA 72.4 or CA 15.3 does not offer any additional benefit for monitoring ovarian carcinoma. Conversely, the serial measurements of these other antigens may represent an interesting biochemical tool for the management of patients with negative CA 125 assay. Serum alphaFP and betaHCG are very useful in the preoperative evaluation and management of nondysgerminomatous ovarian germ cell tumors, whereas elevated serum inhibin levels can be detected in patients with granulosa cell tumors of the ovary. As for endometrial carcinoma, preoperative serum CA 125 levels correlate with stage, depth of myometrial invasion, histologic grade, cervical invasion, peritoneal cytology, lymph node status and clinical outcome. Moreover, serial CA 125 assay is a good indicator of disease activity and a useful biochemical tool for post-treatment surveillance of patients with endometrial carcinoma. SCC is the most reliable serum marker for squamous cell cervical carcinoma, and in patients with this malignancy pretreatment SCC levels are related to tumor stage, tumor size, depth of cervical invasion, lymph-vascular space involvement, lymph node status and clinical outcome. Serial SCC measurements parallel the response to radiotherapy and chemotherapy as well as the clinical course of disease after the completion of treatment. Serum CYFRA 21.1 seems to be less sensitive than serum SCC for squamous cell cervical carcinoma. Elevated CA 125 levels can be often detected in patients with cervical adenocarcinoma. The future for tumor marker research is represented by the emerging technologies of transcriptional profiling and proteomics.

Animals↗