Thyroid function and autoimmunity are associated with the risk of vertebral fractures in postmenopausal women.

Overt or subclinical thyroid dysfunction may affect the risk of fragility fractures. The aim of the present study was to assess the association of thyroid function and autoimmunity with vertebral fractures (VF) in a large sample of Greek postmenopausal women. This cross-sectional study recruited 335 euthyroid postmenopausal women, aged 35-79 years. Euthyroidism was verified by serum thyroid-stimulating hormone (TSH) within the laboratory reference range (0.4-4.5 µIU/mL). VFs were diagnosed by lumbar spine lateral radiographs, according to quantitative procedures. Serum free triiodothyronine (FT3), free thyroxine (FT4), TSH, as well as levels of anti-thyroglobulin (anti-TG) and thyroid peroxidase antibodies (anti-TPO) were compared according to the presence of VFs. Multivariate logistic regression showed that the presence of VFs was predicted independently by ln-TSH levels (OR = 0.290, p = 0.037) and positive anti-TG antibodies (OR = 3.308, p = 0.026) in models adjusted for age, menopausal age, and ln-HOMA-IR. Stepwise logistic regression analysis showed that the presence of VFs was predicted by menopausal age (OR = 1.120, p = 0.001), ln-TSH (OR = 0.312, p = 0.052), and thyroid autoimmunity (anti-TG and anti-TPO positive: OR = 6.637, p = 0.007) in a model that also included age and ln-HOMA-IR. Women with lower circulating TSH had higher risk of having a VF, independently of age, menopausal age, and insulin resistance. The presence of positive anti-TG/anti-TPO antibodies also indicated an elevated risk of fracture. Levels of thyroid hormones had no apparent effect on the risk of fracture. Further studies are necessary to establish the significance of our findings.

Stress urinary incontinence and endogenous sex steroids in postmenopausal women.

AIMS: Urinary incontinence in general is a major cause of quality of life impairment, morbidity and hospitalization. Its onset is strongly linked to the menopause. Our study aimed to elucidate the possible relationship between endogenous circulating estrogens and the onset and development of stress urinary incontinence (SUI). METHODS: One hundred and thirty eight peri- and postmenopausal women with SUI were matched 1:1 with continent women based on age and BMI. Morning fasting blood samples were drawn from all subjects for assessment of estradiol (E2), FSH, LH, Testosterone, Δ4-Androstendione (Δ4Α), DHEAS, prolactin, SBHG as well as a biochemical profile (glucose, insulin, triglycerides, cholesterol, HDL, LDL, ApoA1, ApoB). Hormone and biochemical parameters were compared between continent and incontinent women. RESULTS: Incontinent women had significantly lower serum estradiol levels compared to those in the control group (17.30 ± 8.16 vs. 24.22 ± 8.99, P < 0.001). Furthermore, the same association was observed for serum Δ4Α (146.07 ± 52.63 vs. 159.99 ± 42.62, P = 0.017). These associations remained significant after controlling for age, menopausal age, BMI, and number of deliveries. CONCLUSIONS: These results may indicate that within the postmenopausal range, endogenous sex hormones may be associated with the presence of SUI in women not on menopausal hormone therapy. Neurourol. Urodynam. 36:121-125, 2017. © 2015 Wiley Periodicals, Inc.

Association of sex hormones and glucose metabolism with the severity of multiple sclerosis.

PURPOSE/AIM OF THE STUDY: We evaluated possible associations between the severity of multiple sclerosis (MS) and levels of sex hormones as well as biochemical parameters in a sample of ambulatory patients. MATERIAL AND METHODS: This cross-sectional study recruited 133 adults (52 men, 66 premenopausal and 15 postmenopausal women), with relapsing-remitting MS. Fasting venous blood samples were drawn for biochemical and hormonal evaluation. These parameters were tested for possible associations with MS severity, assessed using the Expanded Disability Status Scale (EDSS)-scores. RESULTS: Follicle-stimulating hormone correlated with mean EDSS scores (r = -0.369, p = 0.038) in the premenopausal subgroup. However, this association became non-significant in the age-adjusted multivariate analysis (p = 0.141; power = 67%, type α error 0.10). Free androgen exhibited a borderline negative effect on EDSS-scores in the subgroup of men (r = -0.367, p = 0.093), which was lost after adjusting for age and duration of disease (p = 0.192; statistical power = 93%, type α error 0.05). Levels of estradiol tended to affect disability status of postmenopausal women (normal-mild vs. severe impairment: 23.33 ± 11.73pg/mL vs. 14.74 ± 6.30pg/mL, p = 0.095). Levels of sex hormones or indices of glycemic metabolism did not differ between patients presenting with EDSS scores higher or lower than the median value. CONCLUSION: Sex hormones and indices of glucose metabolism exhibited only a middle effect on EDSS scoring, which was not independent from the presence of confounders like age and duration of MS. The present study highlights the need for additional research, in order to elucidate the role of sex hormones and insulin resistance in the course of MS.

Can anti-Mullerian hormone (AMH) predict the outcome of intrauterine insemination with controlled ovarian stimulation?

OBJECTIVE: To assess whether the levels of anti-Mullerian hormone (AMH) are related to outcome of intrauterine insemination (IUI) in patients treated with gonadotropins. INTERVENTION(S): A total of 195 patients underwent controlled ovarian stimulation (COS) with recombinant follicle stimulating hormone (rFSH) (50-150 IU/d). All patients were submitted upto three cycles of IUI. OUTCOME: Primary outcome was the ability of AMH levels to predict clinical pregnancy at first attempt and the cumulative clinical pregnancy probability of upto three IUI cycles. Secondary outcomes were the relation of AMH, LH, FSH, BMI, age, parity and basic estradiol levels with each other and the outcome of IUI. RESULTS: The area under the receiver operating characteristic (ROC) curve in predicting clinical pregnancy for AMH at first attempt was 0.53 and for cumulative clinical pregnancy was 0.76. AMH levels were positively correlated with clinical pregnancy rate at first attempt and with cumulative clinical pregnancy rate, but negatively correlated with patient's age and FSH levels. Patient's FSH, LH levels were negatively correlated with cumulative clinical pregnancy rate. CONCLUSIONS: AMH levels seem to have a positive correlation and patient's age and LH levels had a negative correlation with the outcome of IUI and COS with gonadotropins. AMH concentration was significantly higher and LH was significantly lower in patients with a clinical pregnancy after three cycles of IUI treatment compared with those who did not achieve pregnancy.

A case of postmenopausal androgen excess.

Ovarian steroid cell tumors are very rare but potentially life-threatening neoplasms. They represent less than 0.1% of all ovarian tumors, typically present in premenopausal women and frequently manifest with virilization. Signs of hyperandrogenism may appear in postmenopausal women due to tumorοus and non-tumorοus adrenal and ovarian causes as well due to the normal aging process. In any case, steroid cell tumor should be suspected in postmenopausal women who present with rapid progressive androgen excess symptoms. This report describes a case of a 67-year-old postmenopausal woman with signs of hyperandrogenism, where an ovarian steroid cell tumor was diagnosed and treated by laparoscopic bilateral salpingo-oophorectomy and synchronous hysterectomy.

Expression of gonadal steroid receptors in the ovaries of post-menopausal women with malignant or benign endometrial pathology: a pilot study.

This pilot study aimed to investigate the expression of estrogen (ER) and progesterone receptors (PR), as well as their subtypes [alpha (ERα), beta (ERß)], in the ovaries of postmenopausal women with benign or malignant endometrial pathology. Twenty postmenopausal women (age 66.2 ± 7.4 years) were included, diagnosed with benign (n = 10) or malignant [(serous/papillary (n = 4), endometrioid (n = 6)] endometrial lesions. Higher ERß and PR ovarian expressions were observed comparing women with endometrioid versus non-endometrioid endometrial carcinoma (p = 0.022 and p = 0.029, respectively). Age, age at menarche and presence of hypertension were negatively associated with ERs and PR expression. The expression of ERα and ERß was inversely correlated with menopausal age, which was not verified for PR. No significant association was observed between ERs or PR expression and benign or malignant endometrial pathology. Higher expression of ERß and PR in the postmenopausal ovary is associated with the presence of a less aggressive type of endometrial cancer, comparing women with endometrioid versus non-endometrioid lesions. The expression pattern of ovarian receptors did not differ regarding the development of benign or malignant endometrial lesions. Larger observational studies are necessary to confirm the significance of our findings.

In vitro maturation in subfertile women with polycystic ovarian syndrome undergoing assisted reproduction.

BACKGROUND: Polycystic ovarian syndrome (PCOS) occurs in 4% to 7% of all women of reproductive age and 50% of women presenting with subfertility. Subfertility affects 15% to 20% of couples trying to conceive. A significant proportion of these women ultimately need assisted reproductive technology (ART). In vitro fertilisation (IVF) is one of the assisted reproduction techniques employed to raise the chances of achieving a pregnancy. For the standard IVF technique, stimulating follicle development and growth before oocyte retrieval is essential, for which a large number of different methods combining gonadotrophins with a gonadotrophin-releasing hormone (GnRH) agonist or antagonist are used. In women with PCOS, the supra-physiological doses of gonadotrophins used for controlled ovarian hyperstimulation (COH) often result in an exaggerated ovarian response, characterised by the development of a large cohort of follicles of uneven quality, retrieval of immature oocytes, and increased risk of ovarian hyperstimulation syndrome. A potentially effective intervention for women with PCOS-related subfertility involves earlier retrieval of immature oocytes at the germinal-vesicle stage followed by in vitro maturation (IVM). So far, the only data available have derived from observational studies and non-randomised clinical trials. OBJECTIVES: To compare outcomes associated with in vitro maturation (IVM) followed by vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI) versus conventional IVF or ICSI, among women with polycystic ovarian syndrome (PCOS) undergoing assisted reproductive technologies (ART). SEARCH METHODS: We searched the Menstrual Disorders and Subfertility Group (MDSG) Specialised Register of controlled trials to May 2013 for any relevant trials identified from the title, abstract, or keyword sections. This was followed by a search of the electronic database MEDLINE, EMBASE, LILACS and CINAHL, without language restriction. We also performed a manual search of the references of all retrieved articles; sought unpublished papers and abstracts submitted to international conferences, searched the clinicaltrials.gov and WHO portal registries for submitted protocols of clinical trials, and contacted experts. In addition, we examined the National Institute of Clinical Excellence (NICE) fertility assessment and treatment guidelines and handsearched reference lists of relevant articles (from 1970 to May 2013). SELECTION CRITERIA: All randomised trials (RCTs) on the intention to perform IVM before IVF or ICSI compared with conventional IVF or ICSI for subfertile women with PCOS. DATA COLLECTION AND ANALYSIS: Three review authors (CS, MK and NV) independently assessed eligibility and quality of trials. Primary outcome measure was live birth rate per randomised woman. MAIN RESULTS: There were no RCTs suitable for inclusion in the review, although there are currently three ongoing trials that have not yet reported results. AUTHORS' CONCLUSIONS: Though promising data on the IVM technique have been published, unfortunately there is still no evidence from RCTs upon which to base any practice recommendations regarding IVM before IVF or ICSI for women with PCOS. Meanwhile, the results of the above-mentioned ongoing trials are awaited and, of course, further evidence from good quality trials in the field is eagerly anticipated.

Serum lipid levels and bone mineral density in Greek postmenopausal women.

Contradictory results have been reported regarding a relationship between serum lipid levels and bone mineral density. The purpose of this study was to further investigate a possible relationship between those parameters in Greek postmenopausal women. A total of 591 patients followed at a tertiary hospital were examined for seven different lipid factors in relation to dual-emission X-ray absorptiometry measurements at the lumbar spine. Lipoprotein-a was the only lipid measurement that univariately showed an almost significant trend of association with bone mass category (analysis of variance [ANOVA] p value 0.062 for Ln(Lipoprotein-a)). In multiple regression, it was noted that a non-significant negative trend of association of high density lipoprotein (HDL) cholesterol and Apolipoprotein AI with lumbar T-score (p value 0.058 and 0.075, respectively). In age subgroup analysis, Lipoprotein-a and Ln(Lipoprotein-a) presented a negative correlation with lumbar T-score for women with age ≥ 53 years (p value 0.043 and 0.070, respectively), while a negative correlation of HDL and Apolipoprotein AI levels with lumbar T-score remained in women with age < 53 years (p value 0.039 and 0.052, respectively). The findings do not support a strong relationship between lipid levels and bone mass measurements.

The prevalence of glucose metabolism abnormalities in Greek women with polycystic ovary syndrome.

The prevalence of glucose metabolism abnormalities in PCOS women worldwide varies between 10 and 40% but there are no data in Greek PCOS women. In this retrospective study the prevalence of glucose abnormalities and the indices of insulin resistance (IR) and whole-body insulin sensitivity were estimated in a Greek population with PCOS. Impaired glucose tolerance (IGT), impaired fasting glucose (IFG) and type 2 diabetes mellitus (t2DM) were calculated. The prevalence of IGT, IFG and t2DM in our PCOS population was 7.6, 5.1 and 1.7%, respectively. The total prevalence of glucose abnormalities was estimated as 14.1%. The prevalence of t2DM was three- to four-fold higher than in the general Greek female population of the same age as this was estimated by 2, recently published studies. PCOS women with increased BMI and waist circumference and age greater than 30 years, present more severe IR and decreased whole-body insulin sensitivity. Our data indicates a relatively high prevalence of glucose intolerance and t2DM in a Greek population with PCOS. Obese women with PCOS are in higher risk to develop glucose abnormalities and probably t2DM later in life and therefore every woman diagnosed with PCOS should undergo a 2-h post load OGTT.

Sp1 collagen I A1 polymorphism in women with stress urinary incontinence.

INTRODUCTION AND HYPOTHESIS: Stress urinary incontinence (SUI) is in part attributed to qualitative and quantitative changes in connective tissue of the urogenital tract. We examined the association of collagen type I a1 (COLIA 1) Sp1 polymorphism with the risk of SUI. METHODS: Forty-five postmenopausal women suffering from urodynamically verified SUI (study group) were compared to 45 healthy volunteers (control). DNA was extracted from peripheral blood. The genotyping concerning the type 1 a1 collagen gene Sp1 polymorphism was performed with polymerase chain reaction. RESULTS: The polymorphic T allele was overrepresented in the SUI patients (63.2% versus 36.8%, p = 0.016). Odds ratio for SUI in women harboring the T allele was 2.19 (95% CI 1.149-4.176) compared to women with the wild-type genotype. CONCLUSIONS: The COLIA1 Sp1 polymorphism is associated with increased prevalence of stress urinary incontinence in postmenopausal women.

Reproductive hormones and postpartum mood disturbances in Greek women.

AIM: Postpartum mood disturbances are common among Greek women, with postpartum depression (PPD) being as high as 19%. This study aimed to investigate whether sex steroid hormone levels affect the incidence of postpartum mood disturbances. MATERIALS AND METHODS: Fifty-seven women were evaluated for postpartum mood disturbances using the Postpartum Blues Questionnaire and the Edinburgh Postnatal Depression Scale on the 1st and 6th week. Serum estradiol, progesterone and testosterone concentrations were measured upon admission for delivery and daily until the fourth postpartum day. We then studied the association between hormone levels and the scores in the two psychometric scales. RESULTS: Testosterone was the only hormone that was marginally associated with psychometric scoring in simple regression analysis. (Postpartum Blues during days 1-4: b = 4.291, 95% C.I. -0.796 to 9.377 and p-value = 0.096). Women with lower testosterone drops had higher scores in Postpartum Blues Questionnaire. This association, however, lost statistical significance in the multivariable analysis after adjusting for pregnancy duration. In multiple regression analysis, only pregnancy duration had the most constant adverse effect on psychometric scores: The shorter the duration of pregnancy, the higher the scores for Postpartum Blues. (r = -0.39, p < 0.01). CONCLUSIONS: Our findings do not indicate an association between the occurrence of postpartum mood disorders and sex steroid hormone levels. Preterm labour may be associated with a higher risk of postpartum mood disturbances.

The effect of vitamin D receptor BsmI genotype on the response to osteoporosis treatment in postmenopausal women: a pilot study.

AIM: The purpose of our study was to investigate the possible effect of BsmI vitamin D receptor (VDR's) polymorphism on changes in bone mineral density (BMD) and bone turnover markers in postmenopausal women receiving different treatments. MATERIAL AND METHODS: This pilot study included 42 postmenopausal women with elevated fracture risk, randomized into 1-year treatment with weekly oral alendronate or daily subcutaneous teriparatide. Both groups received daily supplements of 1000 mg calcium and 800 IU vitamin D. Blood samples were obtained for biochemical evaluation and genotyping. BMD at the lumbar spine and femoral neck were assessed with dual energy X-ray absorptiometry. Baseline, follow-up BMD and markers of bone turnover were assessed according to the BsmI genotype. RESULTS: BMD at the lumbar spine increased in patients carrying at least one b allele, while it decreased in patients with the BB genotype (P = 0.041). Whereas no gene-treatment interaction was observed in teriparatide-receiving patients, women with the BB genotype receiving alendronate resulted in negative BMD (-0.056 ± 0.032 g/m(2) ) and T-score (-0.295 ± 0.190) gradient, compared to carriers of the b allele (BMD: +0.020 ± 0.017 g/m(2) , P = 0.054; T-score: +0.217 ± 0.100, P = 0.030). No effect of genotype was apparent with respect to gradients of biochemical bone markers. CONCLUSIONS: These preliminary results indicate that alendronate has a differential effect on BMD, depending on the VDR genotype. Carriers of the b allele may be more responsive to treatment compared to patients with the BB genotype. The interaction of VDR's BsmI polymorphism with the efficacy of the anti-osteoporotic treatment needs further investigation by larger prospective studies.

The frequency of early, spontaneous miscarriage associated with the leu33pro polymorphism of Glycoprotein IIIa: a pilot study.

BACKGROUND: Inherited thrombophilia is associated with both poor obstetrical outcomes and increased cardiovascular risk later in life. In fact, a personal history of spontaneous miscarriage is reported to increase the risk of subsequent ischaemic heart disease. AIMS: This pilot study aims to evaluate the association between genetic polymorphism-related increased risk of arterial thrombosis and the history of spontaneous miscarriage early in pregnancy, among healthy postmenopausal women. METHODS: The following polymorphisms were assessed in 84 healthy post-menopausal women: Glycoprotein IIIa leu33pro, Apolipoprotein E2/E3/E4, Methylenetetrahydrofolate reductase, Apolipoprotein B arg3500gln, Paraoxonase 1 gln182arg, Plasminogen activator inhibitor 1 4G/5G, Cholesterol-7(α) -hydroxylase and Cholesterol ester transfer protein (ΤaqIB) B1/B2. The association between the polymorphisms and history of spontaneous pregnancy loss was evaluated. RESULTS: The frequency of the PL(A2) allele of glycoprotein IIIa was significantly higher in women who experienced spontaneous miscarriage when compared with controls (P = 0.033). Glycoprotein IIIa leu33pro polymorphism correlated positively with the frequency of spontaneous miscarriage (P = 0.027). Among women reporting miscarriage, 55.6% were heterozygous compared with 44.4% who were wild type. We found no significant association between any of the other polymorphisms and spontaneous pregnancy loss. CONCLUSIONS: Our findings indicate that Glycoprotein IIIa leu33pro polymorphism is associated with early, spontaneous miscarriage. The causative role of this polymorphism as a risk factor of pregnancy loss needs further investigation by prospective studies.

Apolipoprotein E and paraoxonase 1 polymorphisms are associated with lower serum thyroid hormones in postmenopausal women.

OBJECTIVE: Autoimmune thyroiditis and overt or subclinical hypothyroidism have been associated with increased prevalence of cardiovascular disease (CVD). DESIGN: Cross-sectional investigation of the association between gene polymorphisms related to CVD with thyroid function and autoimmunity. PATIENTS: In total 84 healthy postmenopausal women aged 49-69 years. MEASUREMENTS: FT3, FT4, anti-TPO and anti-TG were assessed in the sera of participants. The following polymorphisms were assessed from peripheral lymphocyte DNA: Apolipoprotein E E2/E3/E4, paraoxonase 1 A/B, Glycoprotein IIIa leu33pro, MTHFR ala222val, ApoBarg3500gln, plasminogen activator inhibitor 1 4G/5G, cholesterol 7-alpha hydroxylase A204C and cholesterol ester transfer protein B1/B2. RESULTS: A statistically significant correlation was found between Apolipoprotein E and paraoxonase 1 polymorphisms and serum thyroid hormones: carriers of the E2 or E4 allele of the ApoE gene had lower levels of FT4 (P = 0.0005) than women with the E3/E3 genotype. Carriers of the B allele of paraoxonase 1 gene had lower levels of FT3 compared to women with the wild-type genotype (P = 0.047). A statistically significant positive association (P = 0.049) was also observed between anti-TG antibodies and the presence of the E2 allele of the Apolipoprotein E gene. CONCLUSIONS: Polymorphisms of apolipoprotein E and paraoxonase 1 are associated with different levels of thyroid hormone and anti-Tg antibody levels in the study population in this pilot study. The mechanism underlying this association remains to be elucidated.

Endogenous sex hormones and risk factors for atherosclerosis in healthy Greek postmenopausal women.

OBJECTIVE: To assess the association between endogenous sex hormones and risk factors for atherosclerosis in healthy postmenopausal women. DESIGN: Cross-sectional study in a university menopause clinic. METHODS: Serum sex hormones and lipid-lipoprotein profile, arterial pressure, homocysteine and insulin resistance, measured by the homeostasis model assessment of insulin resistance (HOMA-IR), were assessed in 598 healthy postmenopausal women not on hormone therapy. RESULTS: Compared with women in the lowest testosterone quartile (Q), women in the highest testosterone quartile had higher total cholesterol (Q1: 225.2 +/- 41.3 vs Q4: 246.2 +/- 38.4 mg/dl, P < 0.01), low-density lipoprotein (LDL)-cholesterol (Q1: 146.9 +/- 37.2 vs Q4: 171.8 +/- 35.3 mg/dl, P < 0.001), atherogenic index of plasma (AIP) (Q1: -0.224 +/- 0.238 vs Q4: -0.087 +/- 0.254, P < 0.01), apolipoprotein B (ApoB) (Q1: 100.7 +/- 23.1 vs Q4: 113.9 +/- 23.8 mg/dl, P < 0.001) and higher high-density lipoprotein (HDL)-cholesterol (Q1: 60.7 +/- 14.5 vs Q4: 52.9 +/- 13.0 mg/dl, P < 0.01). Accordingly, women in the highest free androgen index (FAI) quartile had higher AIP (Q1: -0.232 +/- 0.254 vs Q4: -0.078 +/- 0.243, P < 0.001) and ApoB (Q1: 102.4 +/- 25.5 vs Q4: 114.2 +/- 25.8 mg/dl, P < 0.01) and lower HDL-cholesterol (Q1: 62.0 +/- 15.7 vs Q4: 51.9 +/- 11.6 mg/dl, P < 0.001) and apolipoprotein A (Q1: 159.6 +/- 25.6 vs Q4: 147.9 +/- 24.1 mg/dl, P < 0.01) compared with women in the lowest FAI quartile. These differences remained significant after adjustment for age, body mass index (BMI), insulin resistance and social habits. The free estrogen index (FEI) exhibited similar associations to the FAI. HOMA-IR showed an independent positive association with total testosterone (Q1: 2.00 +/- 1.36 vs Q4: 2.66 +/- 1.60, P < 0.01), FAI (Q1: 1.70 +/- 1.12 vs Q4: 3.04 +/- 1.66, P < 0.001) and FEI (Q1: 1.70 +/- 0.91 vs Q4: 3.08 +/- 1.77, P < 0.001). CONCLUSIONS: Increased androgenicity in healthy postmenopausal women is associated with an unfavorable cardiovascular risk profile. High endogenous estradiol is related to a pro-atherogenic lipid profile, an association which may, in part, be mediated by insulin resistance.

The effect of low dose hormone therapy on mammographic breast density.

OBJECTIVES: To evaluate the effect of two standard and one low dose continuous hormone therapy regimens on mammography. METHODS: One hundred and thirty-two non-hysterectomized postmenopausal women were randomly allocated either to conjugated equine estrogens 0.625 mg plus medroxyprogesterone acetate 5 mg (CEE/MPA, n=38), 17beta-estradiol 2 mg plus norethisterone acetate 1 mg (E2/NETA, n=44) or 17beta-estradiol 1 mg plus norethisterone acetate 0.5 mg (low E2/NETA, n=50). Treatment was continuous and the study period lasted 12 months. Main outcome measures were the changes according to Wolfe classification between baseline and 12-month mammograms. RESULTS: Five (13.2%) women in the CEE/MPA group showed an increase in breast density. Fourteen (31.8%) women on E2/NETA and 6 (12.2%) on low E2/NETA treatment revealed an increase in breast density. No woman exhibited an involution of fibroglandular tissue. CONCLUSIONS: Different hormone therapy regimens have a variable impact on breast density probably depending on the steroid used. Low dose hormone therapy associates with significantly lesser increase in breast density.

A 5-year study on the effect of hormone therapy, tibolone and raloxifene on vaginal bleeding and endometrial thickness.

OBJECTIVES: To study the effect of standard and low-dose estrogen-progestin therapy (EPT), tibolone and raloxifene on the incidence of vaginal spotting/bleeding and endometrial thickness over a 5-year period. METHODS: Seven hundred eighty-six postmenopausal women were studied in an open prospective design. Vaginal spotting/bleeding and endometrial thickness as assessed by transvaginal ultrasonography was compared between six categories of women over a 5-year period: three categories in women on continuous combined estrogen-progestin therapy, one category under tibolone, one category under raloxifene and one under no treatment. More specifically, women received tibolone 2.5 mg (N = 204), raloxifene HCl 60 mg (N = 137), conjugated equine estrogens 0.625 mg/medroxyprogesterone acetate 5mg (N = 122), 17beta-estradiol 2mg/norethisterone acetate 1mg (N = 58), 17beta-estradiol 1mg/norethisterone acetate 0.5mg (N = 76) or no therapy (controls, N = 189). Women with suspected endometrial pathology were referred for hysteroscopy. RESULTS: Bleeding/spotting incidence was highest among standard dose EPT users (conjugated equine estrogens 0.625 mg/medroxyprogesterone acetate 5mg: 40.1%, 17beta-estradiol 2mg/norethisterone acetate 1mg: 44.8%, p < 0.001 compared to controls). Low-dose EPT associated with lower incidence of spotting/bleeding (34.1%). The incidence under tibolone and raloxifene was 22.5% and 2.9%, respectively, while 3.2% of women not receiving therapy reported vaginal spotting/bleeding. Mean endometrial thickness was not significantly affected in any of the groups studied. The drop-out rate due to spotting/bleeding was higher in the two higher dose EPT regimens. After logistic regression analysis, age at baseline was the only significant predictor of subsequent spotting/bleeding (b = -0.25, S.E. = 0.09, p = 0.006), while menopausal age and pre-treatment serum FSH had marginal significance. CONCLUSIONS: EPT, tibolone and raloxifene do not appear to associate with significant changes in endometrial thickness in the majority of cases. The low-dose EPT regimen associated with a decreased incidence of unscheduled spotting/bleeding compared to the standard dose regimens. Tibolone expressed a favorable endometrial profile, as seen in its effect on unscheduled spotting/bleeding and mean endometrial thickness. Raloxifene associated with the lowest incidence in S/B and the lowest drop-out rate.s.

Bsm1 vitamin D receptor polymorphism and calcium homeostasis following bariatric surgery.

PURPOSE/AIM: To evaluate the association between the Bsm1 vitamin D receptor polymorphism and the calcium-vitamin D-parathormone axis following bariatric surgery. MATERIALS AND METHODS: This cross-sectional study included 86 morbidly obese patients, who underwent either gastric bypass or sleeve gastrectomy, with a mean follow-up of four years. Calcium metabolism indices and bone turnover markers were assessed according to the presence of secondary hyperparathyroidism and the Bsm1 vitamin D receptor genotypes. RESULTS: Secondary hyperparathyroidism (42.2% of sample) was associated with lower levels of 25hydroxyvitamin D and elevated markers of bone turnover. In subjects without secondary hyperparathyroidism, presence of the unfavorable B allele resulted in higher levels of parathormone (Bb and BB vs. bb genotype: 50.3 ± 8.2 pg/dl vs. 44.4 ± 10.7 pg/dl, p = .011, adjusted for weight loss, baseline body mass index, 25hydroxyvitamin D, surgical procedure, and duration after surgery). In the whole sample, patients bearing the unfavorable B allele exhibited lower weight loss, a parameter that was negatively associated with markers of bone resorption. CONCLUSIONS: Secondary hyperparathyroidism is highly prevalent after bariatric surgery. Bsm1 vitamin D receptor polymorphism may have an effect in early stages of calcium metabolism imbalance, while no association is detected in patients who have already developed secondary hyperparathyroidism. Moreover, vitamin D receptor polymorphism is associated with post-surgery weight loss, a process related to bone turnover.

Indices of adiposity and thyroid hormones in euthyroid postmenopausal women.

OBJECTIVE: We aimed to evaluate the association between thyroid hormones and indices of obesity in a sample of euthyroid postmenopausal women. DESIGN: Cross-sectional study. METHODS: Serum levels of TSH, free triiodothyronine (FT3), and free thyroxine (FT4) as well as BMI and waist:hip ratio (WHR) were evaluated in 194 healthy euthyroid postmenopausal women. Ultrasonography was used to assess abdominal fat layers (subcutaneous fat (SF), preperitoneal fat (PF), and SF:PF ratio). Indices of adiposity were defined as high vs low depending on the median value of the assessed parameters. RESULTS: After multivariate adjustment for traditional risk factors, lower FT4 levels and a higher FT3:FT4 ratio predicted higher SF mass (FT4, Exp(ß)=0.035, P=0.020 and FT3:FT4, Exp(ß)=2.374, P=0.018), whereas higher FT3 predicted higher PF mass (Exp(ß)=2.815, P=0.032). Women with FT3:FT4 above the highest quartile had a significantly higher SF mass as compared to women in the lowest quartile (1.81 ± 0.62 cm vs 1.54 ± 0.46 cm, P=0.027). BMI had a positive independent association with TSH (Exp(ß)=1.829, P=0.018). Finally, FT3 was significantly associated with SF mass among women with higher BMI (FT3, ß=0.259, P=0.040) and women with higher WHR (ß=0.309, P=0.020) but not among women with lower BMI or WHR values. CONCLUSION: Thyroid hormone levels, and in particular FT3, were independently associated with SF and PF in euthyroid postmenopausal women, and this association was mainly evident in women with higher BMIs. On the other hand, among traditional indices of adiposity, only TSH was positively associated with BMI. Larger prospective studies are needed to evaluate the significance of the present findings.

Vertebral fracture prevalence among Greek healthy middle-aged postmenopausal women: association with demographics, anthropometric parameters, and bone mineral density.

BACKGROUND CONTEXT: The prevalence of skeletal fractures shows a marked geographic variability; however, data regarding the Greek population remain limited. PURPOSE: To evaluate the frequency of asymptomatic vertebral fractures (VFs), and potential risk factors, in a large sample of Greek postmenopausal women. STUDY DESIGN: A cross-sectional study at the University Menopause Clinic. PATIENT SAMPLE: Four hundred fifty-four postmenopausal women aged 35 to 80 years, with an average menopausal age of 9.2±7.1 years. OUTCOME MEASURES: They included medical history, anthropometric and biochemical parameters, bone mineral density (BMD) at lumbar spine (LS) and femoral neck (FN), and LS lateral radiographs. METHODS: Lumbar spine lateral radiographs were evaluated according to quantitative procedures, aiming to identify VFs. Anthropometric and biochemical parameters and values of BMD were compared according to the presence of VFs. RESULTS: A total of 37 (8.15%) women had at least one VF. Lumbar spine and FN-osteoporosis was identified in up to 23.1% and 40.9% subjects with prevalent VFs, respectively. The prevalence of VFs was largely associated with age, with women aged 60 years or more presenting an up to fourfold risk compared with younger women. Moreover, the presence of VFs was associated with higher menopausal age, advanced age at menarche, a history of early menopause, and prolonged lactation. Lower LS-BMD and, especially, FN-BMD were negatively associated with VF prevalence (prevalent VF vs. no VF: LS-BMD, 0.89±0.16 g/cm(2) vs. 0.98±0.16 g/cm(2), p=.010; FN-BMD, 0.72±0.10 g/cm(2) vs. 0.81±0.12 g/cm(2), p=.008). CONCLUSIONS: Asymptomatic VFs are common among Greek healthy middle-aged postmenopausal women. More than 50% subjects with prevalent VFs present with normal BMD or osteopenia. Age and bone density classification at the FN presented the strongest association with the prevalence of VFs.