Non-alcoholic fatty liver disease is associated with insulin resistance and lipid accumulation product in women with polycystic ovary syndrome.

STUDY QUESTION: What are the most relevant factors associated with non-alcoholic fatty liver disease (NAFLD) in women with polycystic ovary syndrome (PCOS)? SUMMARY ANSWER: Insulin resistance (IR) and lipid accumulation product (LAP) are independently associated with NAFLD in PCOS. WHAT IS KNOWN ALREADY: Obesity and IR are frequently present in both women with PCOS and subjects having NAFLD. The coexistence of PCOS and NAFLD might synergistically increase the risk for both type 2 diabetes (T2DM) and cardiovascular disease (CVD). LAP, calculated from waist circumference (WC) and triglycerides (TGs) concentrations [(WC-58) × TGs], has been shown to represent an integrated marker of cardiometabolic risk in women with PCOS. STUDY DESIGN, SIZE, DURATION: This cross-sectional study included 600 Caucasian women diagnosed with PCOS by the Rotterdam criteria between May 2008 and May 2013. PARTICIPANTS, SETTINGS, METHODS: The study was done at the university hospitals in Belgrade, Serbia and Thessaloniki, Greece. All subjects underwent anthropometric measurements and analyses of fasting blood glucose, insulin, lipids, total testosterone and SHBG, as well as liver tests (transaminases, γ-glutamyltransaminase, total bilirubin and alkaline phosphatase). Calculations for a NAFLD liver fat score (NAFLD-LFS) (with, accordingly, determination of metabolic syndrome and testing for T2DM) as well as homeostasis model assessment of IR (HOMA-IR), LAP as a marker of visceral adiposity, and free androgen index (FAI) were performed. We evaluated the prevance of NAFLD and analyzed associations of the above variables with NAFLD. MAIN RESULTS AND THE ROLE OF CHANCE: NAFLD was more prevalent in patients with PCOS than in controls (50.6 versus 34.0%, respectively). Women with PCOS had higher readings for WC, LAP, insulin and HOMA-IR, total cholesterol and TGs than controls (P < 0.001). In PCOS women, the NAFLD-LFS significantly (P < 0.001) correlated with WC, BMI, glucose, HOMA-IR, TGs, LAP and FAI. In multivariate logistic regression, HOMA-IR and LAP were independently associated with NAFLD (P ≤ 0.001). LIMITATIONS, REASONS FOR CAUTION: A possible weakness of the study may be the absence of structural confirmation of liver status. Hovewer, liver biopsy is invasive, difficult to perform in large populations and carries some risk of complications while magnetic resonance spectroscopy does not provide any information regarding the presence of fibrosis and is not routinely available. Another possible limitation could be the measurement of total testosterone by radioimmunoassay, which can be inaccurate when determining low levels of testosterone. Finally, fewer controls than subjects in the study group could have affected the significance of the results. WIDER IMPLICATIONS OF THE FINDINGS: There is a debate on the most accurate clinical method for diagnosing liver disease as an early predictor of T2DM and CVD in general population and in PCOS women. There current study provided data on this issue from a cohort of Caucasian women with PCOS. STUDY FUNDING/COMPETING INTERESTS: The study was supported by a research grant by the Serbian Ministry of Science and Education (grant nos 41009 and 175032). All authors have no competing interests.

Gene variants associated with age at menopause are also associated with polycystic ovary syndrome, gonadotrophins and ovarian volume.

STUDY QUESTION: Is there a relationship between the genetic risk for polycystic ovary syndrome (PCOS) and genetic variants that influence timing of menopause? SUMMARY ANSWER: The genetic risk score, which sums the contribution of variants at all menopause loci, was associated with PCOS. WHAT IS ALREADY KNOWN: Ovarian parameters and anti-Mullerian hormone levels suggest that women with PCOS should have a later age at menopause. STUDY DESIGN, SIZE, DURATION: The study was a case-control examination of genetic variants associated with age at menopause in a discovery cohort of women with PCOS (n = 485) and controls (n = 407) from Boston recruited from 2003 to 2012. Replication was performed in women from Greece (cases, n = 884 and controls, n = 311). PARTICIPANTS/MATERIALS, SETTINGS, METHODS: PCOS was defined by the National Institutes of Health criteria in Boston and Greece (n = 783), with additional subjects fulfilling the Rotterdam criteria (hyperandrogenism, polycystic ovary morphology and regular menses) in Greece (n = 101). Controls in Boston and Greece had regular menstrual cycles and no hyperandrogenism. Allele frequencies for variants previously associated with age at menopause were examined in PCOS cases and controls, along with the relationship to quantitative traits. MAIN RESULTS AND ROLE OF CHANCE: The variant rs11668344-G was associated with decreased risk of PCOS (odds ratio: 0.77 [0.59-0.93]; P = 0.004). There was a strong relationship between the late menopause allele rs12294104-T and increased LH levels (ß ± SE; 0.26 ± 0.06; P = 5.2 × 10(-5)) and the LH:FSH ratio (0.28 ± 0.06; P = 2.7 × 10(-6)). The minor allele at rs10852344-T was associated with smaller ovarian volume (-0.16 ± 0.05; P = 0.0012). A genetic risk score calculated from 16 independent variants associated with age at menopause was also associated with PCOS (P < 0.02), LH and the LH:FSH ratio (both P < 0.05). LIMITATIONS, REASONS FOR CAUTION: The variant rs11668344 was not associated with PCOS in the Greek cohort, but results exhibited the same direction of effect as the Boston cohort. However, it is possible that the individual association was a false positive in the Boston cohort. WIDER IMPLICATIONS OF THE FINDINGS: The study demonstrates that gene variants known to influence age at menopause are also associated with risk for PCOS. Further, our data suggest that the relationship between age at menopause and PCOS may be explained, at least in part, by effects on LH levels and follicle number. The data point to opposing influences of the genetic variants on both menopausal age and PCOS. STUDY FUNDING/COMPETING INTERESTS: The project was supported by award number R01HD065029 from the Eunice Kennedy Shriver National Institute of Child Health & Human Development, award number 1 UL1 RR025758, Harvard Clinical and Translational Science Center, from the National Center for Research Resources and award 1-10-CT-57 from the American Diabetes Association. C.K.W. is a consultant for Takeda Pharmaceuticals. TRIAL REGISTRATION NUMBER: NCT00166569.

Han Chinese polycystic ovary syndrome risk variants in women of European ancestry: relationship to FSH levels and glucose tolerance.

STUDY QUESTION: Are PCOS risk variants identified in women of Han Chinese ethnicity also associated with risk of PCOS or the phenotypic features of PCOS in European women? SUMMARY ANSWER: One variant, rs2268361-T, in the intron of FSHR was associated with PCOS and lower FSH levels, while another variant rs705702-G near the RAB5B and SUOX genes was associated with insulin and glucose levels after oral glucose testing in women with PCOS of European ethnicity. WHAT IS KNOWN ALREADY: Three of the eleven variants associated with PCOS in the Han Chinese genome-wide association studies were also associated with PCOS in at least one European population when corrected for multiple testing (DENND1A, THADA and YAP1). However, additional replication is needed to establish the importance of these variants in European women and to determine the relationship to PCOS phenotypic traits. STUDY DESIGN, SIZE, DURATION: The study was a case-control examination in a discovery cohort of women with PCOS (n = 485) and controls (n = 407) from Boston (Boston 1). Replication was performed in women from Greece (cases n = 884 and controls n = 311) and an additional cohort from Boston (Boston electronic medical record (EMR); n = 350 cases and n = 1258 controls). PARTICIPANTS/MATERIALS, SETTINGS, METHODS: Women had PCOS defined by the National Institutes of Health criteria in Boston 1 and Greece (n = 783), with additional subjects fulfilling the Rotterdam criteria (hyperandrogenism, polycystic ovary morphology and regular menses) in Greece (n = 101). Controls in Boston and Greece had regular menstrual cycles and no hyperandrogenism. The second cohort from Boston was defined using the EMR and natural language processing. Allele frequencies for variants associated with PCOS in Han Chinese women were examined in PCOS cases and controls, along with the relationship to quantitative traits. MAIN RESULTS AND THE ROLE OF CHANCE: A variant rs2268361-T in an intron of FSHR was associated with PCOS (0.84 [0.76-0.93], OR [95% CI]; P = 0.002). The rs2268361-T was associated with lower FSH levels (-0.15 ± 0.05; P = 0.0029). A variant rs705702-G near RAB5B and SUOX was associated with insulin (-0.16 ± 0.05, P = 0.0029) and glucose levels (-0.20 ± 0.05, P = 0.0002) 120 min after an oral glucose test. LIMITATIONS, REASONS FOR CAUTION: The study was large and contained replication cohorts, but was limited by a small number of controls in the Greek cohort and a small number of cases in the second Boston cohort. The second Boston group was identified using electronic medical record review, but was validated for the cardinal features of PCOS. WIDER IMPLICATIONS OF THE FINDINGS: This study demonstrates a cross-ethnic PCOS risk locus in FSHR in women of European ancestry with PCOS. The variant may influence FSH receptor responsiveness as suggested by the associated change in FSH levels. The relationship between a variant near RAB5B and SUOX and glucose stimulated insulin and glucose levels suggests an influence of one of these genes on glucose tolerance, but the absence of a relationship with PCOS points to potential differences in the international PCOS patient populations. STUDY FUNDING/COMPETING INTERESTS: The project was supported by Award Number R01HD065029 from the Eunice Kennedy Shriver National Institute Of Child Health & Human Development, Award Number 1 UL1 RR025758, Harvard Clinical and Translational Science Center, from the National Center for Research Resources, award 1-10-CT-57 from the American Diabetes Association and the Partners Healthcare Center for Personalized Genetics Project Grant. C.K.W. is a consultant for Takeda Pharmaceuticals. TRIAL REGISTRATION NUMBER: NCT00166569.

CYP21A2 mutations in women with polycystic ovary syndrome (PCOS).

The question of the contribution of CYP21A2 heterozygosity to the development of polycystic ovary syndrome (PCOS) has repeatedly been raised in the literature. The available data, however, do not offer a satisfactory answer. The discrepancy must be attributed, primarily, to the small number of subjects in the various studies, the type of selected phenotype, and the number of searched mutations. The aim of the study was to define the contribution of CYP21A2 heterozygous mutations to the pathogenesis of PCOS. We searched for 14 molecular defects of the CYP21A2 gene in 197 PCOS women, employing allele specific PCR. Androgen levels were determined at baseline by appropriate methodology in the follicular phase. PCOS women with 17-hydroxyprogesterone (17OHP) basal values >2 ng/ml and/or post-ACTH >10 ng/ml were excluded. Appropriate controls were included. The frequency of the CYP21A2 heterozygous mutations in PCOS women and in controls was 7.6% and 5.9%, respectively [p-value (PCOS vs. controls): 0.663]. Homozygosity for CYP21A2 gene defects was not detected. In conclusion, the contribution of CYP21A2 heterozygous mutations to the pathogenesis of PCOS is not substantiated by our data. Moreover, 17-hydroxyprogesterone values of < 10 ng/ml post-ACTH exclude homozygosity of CYP21A2 mutations.

The influence of obesity on androstenedione to testosterone ratio in women with polycystic ovary syndrome (PCOS) and hyperandrogenemia.

The aim of the present study was to evaluate the impact of obesity and insulin resistance on testosterone formation from androstenedione and its contribution to biochemical hyperandrogenemia in all different phenotypic subgroups of PCOS patients. The case-control study included 1087 PCOS women and 206 regularly menstruating, ovulatory controls. The main clinical measurements included anthropometric and basal hormonal characteristics and evaluation of hyperandrogenic and insulin resistance-related features. The results were the following: In PCOS women with biochemical hyperandrogenemia, obesity significantly lowers serum A levels and increases T to A ratio. These findings were not present in PCOS women with clinical hypeandrogenemia and in normal ovulatory controls.

Insulin resistance, androgens, and lipids are gradually improved in an age-dependent manner in lean women with polycystic ovary syndrome: insights from a large Caucasian cohort.

PURPOSE: Polycystic ovary syndrome (PCOS), considered a lifelong condition, manifests mainly as a cluster of hyperandrogenic symptoms during the early reproductive years, with the affected woman gradually developing an adverse cardiometabolic profile over the years. However, some data point to the possibility of differences in the evolution of PCOS according to a woman's weight. The aim of the present study was to evaluate the metabolic and hormonal profiles of women with PCOS over time. METHODS: A total of 763 lean women with PCOS (BMI 20-25 kg/m2) and 376 controls were included. The study group was further divided into three age groups representing women post-adolescence, of reproductive age, and of late reproductive age. All subjects were assessed clinically, biochemically, and hormonally. RESULTS: Waist circumference, lipids, androgens, and insulin resistance index (homeostasis model assessment of IR index (HOMA-IR)) were significantly higher in the PCOS group compared with controls. Age subgroup analysis showed a progressive decrease of HOMA-IR and waist circumference, and lipid levels were comparable between PCOS and controls in all age groups. Androgens remained significantly higher in PCOS, but they gradually decreased through time. A significant negative association of age with waist circumference, androgens, insulin, and HOMA-IR was revealed. Univariate and multivariate regression analysis disclosed a strong correlation of HOMA-IR with age (p = 0.014, ß - 0.19, SE coefficient 0.008) as a single parameter or in combination with total cholesterol (TC) (p < 0.001, age: ß - 0.023, SE 0.10; TC: ß 0.084, SE 0.027). CONCLUSION: Insulin resistance, androgens, and lipids are gradually improved in an age-dependent manner in lean PCOS women. We hypothesize that if these women do not gain weight with the passage of time, there is a high probability that their cardiometabolic risk will be attenuated.

Effect of hypocaloric diet plus sibutramine treatment on hormonal and metabolic features in overweight and obese women with polycystic ovary syndrome: a randomized, 24-week study.

OBJECTIVE: To examine the effect of hypocaloric diet plus sibutramine on body composition, hormonal and metabolic parameters in overweight and obese patients with polycystic ovary syndrome (PCOS). DESIGN: Open-label, randomized study at an outpatient clinic. PATIENTS: A total of 59 overweight and obese (18-39 years old) women with PCOS. MEASUREMENTS: All patients were placed in a hypocaloric diet plus sibutramine (10 mg per day) for the first month and then on a hypocaloric diet plus sibutramine (10 mg per day, group S) or hypocaloric diet only (group D) for the subsequent 6 months. Body composition, hormonal and metabolic features and insulin sensitivity (oral glucose tolerance test, OGTT) were evaluated at baseline and at 3 and 6 months of treatment. RESULTS: Body weight reduced in both groups but the reduction was greater with sibutramine (-15.4+/-1.1 vs -11.1+/-1.9% in groups S and D, respectively, P<0.05). At 6 months, a greater percent of patients lost more than 10% of initial body weight in group S than D (81 vs 52.9%). In both groups, all women with abnormal OGTT at baseline presented normal glucose tolerance after 6 months. Free androgen index (FAI), glucose area under the curve and fasting triglyceride (TG) concentration were reduced after 6 months in group S only (P<0.05). No changes in cardiovascular risk factors, prolactin and hepatic enzymes levels were observed in both groups. CONCLUSION: A hypocaloric diet and a diet plus sibutramine both result in significant weight loss in overweight and obese women with PCOS. Patients who received sibutramine showed a greater weight loss and improvement in hyperandrogenemia and insulin sensitivity after 6 months of treatment. The amelioration of insulin resistance in this group could not be totally explained by weight loss. Total testosterone, FAI and TG levels reduction could be a possible mechanism. Finally, sibutramine increased compliance to diet and it was well tolerated from these patients.

Hypothalamic-pituitary deficiency after Weil's syndrome: a case report.

A case of male hypogonadism after Weil's syndrome is described. Hypogonadism was the result of complete hypothalamic-pituitary deficiency. The relationship between leptospirosis and the endocrinopathy, the incidence that leptospira attacks hypothalamic-pituitary axis, and the mechanism with which the microorganism may cause damage to the pituitary and/or the hypothalamus are discussed.

Adenomyosis.

Adenomyosis is characterized as ectopic endometrial tissues within the myometrium in the uterus. The etiology and pathogenetic mechanism(s) responsible for adenomyosis are poorly understood. Definite diagnosis is made on hysterectomy specimens, although attempts are made at securing preoperative diagnosis by magnetic resonance imaging and myometrial biopsies. Definite treatment of symptomatic women is hysterectomy.

Coexistence of spermatozoa morphological abnormalities in the semen of subfertile men with varicocele.

Spermatozoal morphology in semen specimens from 107 subfertile men with varicocele, aged from 18 to 50 years, were evaluated from Papanicolaou-stained smears, in order to investigate: (a) the frequency of abnormalities in the neck and tail of spermatozoa with an abnormal head; and (b) the ability of prediction of the morphology of one sperm part when the morphology of another is known. It was found that: (1) Morphological abnormalities in the neck are significantly more frequent (p less than 0.01) in spermatozoa with an abnormal head than in spermatozoa with a normal head. (2) Morphological abnormalities in the tail and cytoplasmic droplet are also more frequent, although not significantly, in spermatozoa with an abnormal head. (3) The proportional reduction in error (PRE) was low in all cases. Our results show that spermatozoa with abnormal heads present morphological abnormalities of their other parts more often than spermatozoa with normal heads. However, no prediction can be made on the nature of the morphology of a part of a spermatozoon on the basis of knowledge of the morphology of another of its parts.

The sperm deformity and the sperm multiple anomalies indexes in patients who underwent unilateral orchectomy and preventive radiotherapy.

Two new indices, the sperm deformity and the sperm multiple anomalies index, were assessed in 16 male patients who underwent unilateral orchectomy owing to seminoma and in preventive radiotherapy of paraortic and of the iliac lymph glands homolateral to the testis excised. The aim was to assess the value of these two morphological sperm parameters in distinguishing the semen between the above mentioned group of men from the semen of men with other causes of infertility. It was found that: (1) the values of the sperm deformity index and those of the sperm multiple anomalies index were not significantly different between men who underwent unilateral orchectomy and preventive radiotherapy and the men with other causes of subfertility and (2) the values of the above indices were significantly higher in the semen specimens of men who underwent unilateral orchectomy and preventive radiotherapy and in the semen specimens of men with other causes of subfertility than in the semen specimens of fertile men. It is concluded that testicular response, as far as sperm morphology is concerned, is the same irrespective of the cause exerting a negative effect on spermatogenesis.

Coexistence of spermatozoa morphological abnormalities in the semen of potentially fertile men.

Spermatozoal morphology in semen specimens from 114 potentially fertile men, aged from 20 to 40 years, was evaluated from Papanicolaou stained smears, in order to investigate: (a) the frequency of abnormalities in the neck and tail of spermatozoa with an abnormal or normal head, and (b) the ability of prediction of the morphology of one sperm part when the morphology of another is known. It was found that: (1) Morphological abnormalities in the neck are significantly higher (p less than 0.001) in spermatozoa with an abnormal head than in spermatozoa with a normal head. (2) Morphological abnormalities in the tail and cytoplasmic droplet are also higher, although not significant, in spermatozoa with an abnormal head. (3) The proportional reduction in error (PRE) was low in all cases. Our results show that spermatozoa with abnormal heads more often present morphological abnormalities of their other parts than spermatozoa with normal heads. However, no prediction can be made on the nature of the morphology of a part of a spermatozoon on the basis of knowledge of the morphology of another of its parts.

Semen parameters in 114 fertile men.

We studied the quality of semen in 114 fertile men (their wives were in the first trimester of pregnancy), aged 31.9 +/- 5.7 yr. The results (mean +/- S.D.) were as follows: number of spermatozoa, (72 +/- 61.6) X 10(6)/ml; motile spermatozoa, 56.6% +/- 13.5; spermatozoal velocity, 34.2 +/- 4.3 microns/s; motility index, 19.5 +/- 5.6 microns/s; normal forms, 51.7% +/- 13. It was found that the percentage of motile spermatozoa and the index of motility decrease progressively, at a rate of about 5-10% per hour. In contrast, in the majority of cases, sperm velocity increases during the first 4 h. Low significant correlations was found between percentage of motility and spermatozoal velocity the first hour after ejaculation. Furthermore, moderate significant correlations were found between number of spermatozoa/ml, percentage of motility and normal forms. Finally, low significant negative correlation was found between number of spermatozoa/ml and spermatozoal velocity.

Objective evaluation of spermatozoa motility as influenced by fresh blood serum and normal saline.

In order to investigate the effect of fresh blood serum and normal saline on the motility of ejaculated spermatozoa, semen samples were collected from 7 fertile males, aged 25-39 yrs. Each sample was divided into 5 aliquots: one aliquot remained undiluted, and fresh blood serum from fertile men and normal saline were added to the others to produce 1:1 and 3:1 dilutions. Spermatozoal motility was evaluated objectively, every hour and for 4 h after ejaculation, by the multiple exposure photography method. It was found that serum from fertile men as well as normal saline caused a significant increase of spermatozoal velocity. However, spermatozoal velocity under the influence of serum from fertile men changed with time in a different way than in the undiluted aliquot and those diluted with normal saline. Thus, the beneficial effect of fresh blood serum on spermatozoal velocity, cannot only be attributed to the lowering of seminal viscosity and the reduction of sperm concentration caused by dilution, but to various substances present in blood serum.

Factors that may predispose to rupture of tubal ectopic pregnancy.

OBJECTIVE: The purpose of our study was to evaluate factors that may predispose to rupture of tubal ectopic pregnancy. The study included 99 cases of ectopic pregnancies that were treated during the 5-year period 1992-1996. RESULTS: It was found that: (1) tubal rupture is encountered more often in women with no history of ectopic pregnancy and in those who have full-term pregnancy, suggesting that ectopic pregnancy is less suspected in these women; (2) tubal rupture is encountered less often in lower age ectopic pregnancy; and (3) serum beta-hCG level does not predict tubal rupture. CONCLUSIONS: Rupture of the tube is more often observed in women with a history of ectopic pregnancy and in women with full-term pregnancy. Such observations suggest that ectopic pregnancy is less suspect in these cases.

The role of estrogen replacement therapy in Alzheimer's disease.

Multiple factors appear to contribute to the expression of Alzheimer's disease (AD). About 30% of cases of dementia of the Alzheimer's type (DAT) can be attributed to genetic factors. These observations raise the possibility of identifying multiple interventions that may modify the disease process and, therefore, the clinical expression of the dementia. Prominent among factors that may contribute to dementia and, specifically, to dementia of the Alzheimer's type is cerebral vascular disease. Estrogen is a potent factor that not only prevents vascular disease but also improves blood flow in diseased vessels, including blood flow in regions of the brain affected by AD. Estrogen also has direct effects on neuronal function that may play an important role not only in the preservation of neurons but in the repair of neurons damaged by the disease process. These effects of estrogen on the CNS suggest that the hormone may be effective not only in the prevention of dementia but also in its treatment. Given the distressingly high prevalence of AD among older women and the exorbitant social and economic costs associated with this disorder, a true risk reduction on the order of one-third to one-half, as suggested by several recent analytical studies, would be of tremendous public health importance.

The effect of transdermal estradiol on the conjunctiva in postmenopausal women.

OBJECTIVE: To evaluate the effect of hormonal replacement therapy on the conjunctiva in postmenopausal women. STUDY DESIGN: A prospective clinical study in the setting of a tertiary-care university hospital. Eleven postmenopausal women received hormonal replacement therapy (transdermal estradiol or transdermal estradiol plus medroxyprogesterone acetate) for 4 months. Serum estradiol levels as well as vaginal and conjunctival maturation value (a cytological parameter) were measured before and after the treatment. Data were analysed using the Wilcoxon matched pairs signed-Rank test. RESULTS: A significant increase of serum estradiol levels (P < 0.01) and of vaginal maturation value (P < 0.01) were found. Cytological maturation changes in conjunctival epithelium were also observed. These changes, although mild, were statistically significant (P < 0.01). CONCLUSION: These data support the view that the hormonal replacement therapy induces cytological maturation changes in conjunctival epithelium in postmenopausal women.

The effect of testicular seminoma in semen quality.

Although male subfertility has been reported in a variety of malignancies, most notably testicular carcinoma, the literature that refers to semen quality in males with testicular seminoma is very limited. This study was designed to evaluate the effect of testicular seminoma in semen quality and especially in its three main parameters. Semen specimens from 12 men, aged 24-38 years, with testicular seminoma before they underwent orchidectomy and adjuvant radiotherapy to the ipsilateral para-aortic and pelvic lymph nodes, and from 60 fertile men, aged 24-44 years, were studied. The results support the view that testicular seminoma exerts a deleterious effect on spermatogenesis and consequently to the three main parameters of the semen. The mechanism though of the deleterious effect of seminoma on spermatogenesis remains unclear.

The evaluation of morphological abnormalities of human spermatozoa in fertile and infertile men.

Spermatozoal morphology in semen from 114 fertile men, 107 infertile men with varicocele and 35 infertile men with infection of the accessory genital organs, aged from 18 to 53 years were evaluated by Papanicolaou-stained smears in order to investigate: (a) the frequency of abnormalities in the neck and tail of spermatozoa with an abnormal head and (b) the ability of prediction of the morphology of one sperm part when the morphology of another part is known. The investigation showed that: (1) morphological abnormalities in the neck are significantly higher (P < 0.001, P < 0.01), when the head was abnormal, compared to spermatozoa with a normal head in fertile men and in men with varicocele, respectively; (2) morphological abnormalities in the tail are also higher (0.05 < P < 0.1) in spermatozoa with an abnormal head in men with infection; (3) the proportional reduction of error (PRE) was low in all cases. Our results show that spermatozoa with abnormal heads more often present morphological abnormalities of their counterparts compared to spermatozoa with normal heads. Nevertheless, no prediction can be made on the nature of the morphology of a part of a spermatozoon on the basis of knowledge of its morphology of another part.

Hormone replacement therapy at the threshold of 21st century.

The management of postmenopausal women has become a major focus for the medical profession. The menopause era should progress from a period of "chaos" to an orderly understanding of the many issues related to the menopause and hormone replacement therapy (HRT). Although HRT has beneficial clinical effect and positive benefit/risk ratio, understanding of the side effects and weight gain, and, especially, a fear of cancer limit compliance. New data from long-term, controlled, prospective studies on the effects of different HRT schedules on cancer, cardiovascular disease and osteoporotic fracture risk are needed. HRT should be considered either as for prevention or for individualized care since women experience menopause as individuals, care should be taken not to make inappropriate generalizations. The priority should be the administration of appropriate medication to women with the best result in order to improve health care and quality of life. New therapeutic options will offer substantial medical advancement for the treatment of postmenopausal women.