Mammographic density increase in women receiving different hormone replacement regimens.

OBJECTIVE: we investigated effects of different regimens of hormone replacement therapy (HRT) on mammographic density. METHODS: ninety-five postmenopausal women, who were on different HRT regimens and completed their 4-year mammographic follow-up, were included into this retrospective and comparative study. Twenty-three of these women, who had surgical menopause, received conjugated equine estrogens (CEE) (Group I) only, 26 of them received CEE and continuous medroxyprogesterone acetate (MPA) (Group II), 21 women received CEE and cyclic MPA (Group III), and the remaining 25 women received tibolone (Group IV) therapy. Before commencing on HRT, a baseline high-resolution mammography was performed, and repeated at 6-12-month intervals during the period of 4-year follow-up. All mammographies were evaluated according to the Wolfe classification. RESULTS: a diffuse increase in mammographic density was detected in five women (22%) in group I, nine women (35%) in group II, four women (19%) in group III, and two women (8%) in group IV. The increase in mammographic density was more common among women in group II than those in the other three groups. However, a statistically significant difference was found only between groups II and IV. CONCLUSIONS: different HRT regimens have different effects on breast parenchymal density on mammography. Continuous combination HRT may be more commonly associated with an increase in breast density than other forms of HRT.

Sperm-preparation techniques for men with normal and abnormal semen analysis. A comparison.

OBJECTIVE: To compare two commonly used sperm-preparation techniques, density gradient centrifugation and swim-up procedures, with respect to their effects on acrosome reaction (AR), hypoosmotic swelling (HOS) and nuclear maturity in men with abnormal and normal semen analyses. STUDY DESIGN: In accordance with World Health Organization criteria, 23 men with abnormal (group I) and 20 men with normal (group II) semen analyses were included in a prospective, controlled study. Each semen specimen was divided into aliquots in order to assess AR, HOS and nuclear maturity, determined with acridine orange staining, in both raw and processed semen samples using the density gradient centrifugation and swim-up techniques. RESULTS: Initial semen samples in group I revealed diminished AR, HOS and nuclear maturity rates in comparison to those in group II. In group I, density gradient centrifugation improved AR, HOS and nuclear maturity rates more than did swim-up. However, in group II it improved only the AR; HOS rates were better than with swim-up. There was a significant positive correlation between sperm concentration and HOS rate in raw semen samples from group I. In the same group, motility and morphology correlated with the nuclear maturity rate but not with AR and HOS rates. Semen samples with better motility (> 20%) or morphology (> 25%) showed better nuclear maturity rates (> 50%) in men with abnormal semen analyses. Motility had a sensitivity of 77% and specificity of 90% in predicting nuclear maturity. Morphology had similar sensitivity but lower specificity (70%). CONCLUSION: Density gradient centrifugation is superior to the swim-up technique in improving AR, HOS and nuclear maturity rates in men with abnormal semen analyses. However, when only nuclear maturity rate is taken into account, the swim-up technique seems to be sufficient for selecting spermatozoa in men with normal semen analyses. The nuclear maturity rate also correlates with sperm morphology and motility.

Results of the ACTH stimulation test in hirsute women.

OBJECTIVE: To determine the incidence of late-onset congenital adrenal hyperplasia (LOCAH) due to 21-hydroxylase deficiency among hirsute women and to evaluate the results of the ACTH stimulation test with the clinical characteristics. STUDY DESIGN: Prospective, controlled study. One hundred women with hirsutism and 14 normally cycling women without hirsutism were included in this study at the Division of Reproductive Endocrinology, Department of Obstetrics and Gynecology, Cerrahpasa School of Medicine, Istanbul University. After basal serum progesterone (P) and 17 hydroxyprogesterone (17OHP) levels were determined, an ACTH stimulation test was performed on cycle day 3-5. The same parameters were checked 30 minutes later. We estimated the 21 hydroxylase activity by calculating the change in 17OHP (17OHP 30-0) and the summed rate of the change in P and 17OHP ([P30-0] + [17OHP30-01/30 minutes). The 95th percentile for these estimates in normal women were calculated, and values above three times the 95th percentile were considered to distinguish women with LOCAH due to 21-hydroxylase deficiency. RESULTS: The 95th percentile for 17OHP 30-0 and (P30-0) + (17OHP30-0)/30 minutes in normal women was 1.6 and 8.9 ng/dL/min, respectively. Regarding 17OHP 30-0 values, three women with hirsutism had levels above three times the 95th percentile of these estimates, and 28 women had estimates of more than the 95th percentile but less than threefold. Seventeen of 28 women had oligomenorrhea, and all had severe hirsutism. The women with severe hirsutism and oligomenorrhea had significantly higher ACTH-stimulated serum 17OHP levels and values for 17OHP 30-0 and (P30-0 + (17OHP30-0)/30 min) than did normally cycling women. CONCLUSION: The incidence of LOCAH due to 21-hydroxylase deficiency and mild 21-hydroxylase deficiency is 3% and 28%, respectively, in women with hirsutism. Clinical characteristics are not helpful in determining 21-hydroxylase deficiency. However, the incidence of 21-hydroxylase deficiency is more common among women with severe hirsutism and oligomenorrhea. The change in serum 17OHP 30-0 seems to be greater than the summed rate of change in serum 17OHP and P in the detection of 21-hydroxylase enzyme deficiency.

Role of the mutations Trp8 => Arg and Ile15 => Thr of the human luteinizing hormone beta-subunit in women with polycystic ovary syndrome.

OBJECTIVE: To evaluate the clinical significance of LH in the form of a mutant beta-subunit in women with polycystic ovary syndrome (PCOS). DESIGN: Prospective, controlled study. SETTING: University hospital. PATIENT(S): Thirty healthy women and 30 women with PCOS. INTERVENTION(S): Clinical, ultrasonographic, and hormonal findings were used to define PCOS. Nucleotide mutations within codons 8 and 15 in the LH beta-subunit gene (Trp8 => Arg and Ile15 => Thr) were analyzed with the use of polymerase chain reaction and subsequent restriction fragment length polymorphism. MAIN OUTCOME MEASURE(S): Serum levels of gonadotropins, androgens, E2, and prolactin were determined, and the results of restriction fragment length polymorphism were analyzed. RESULT(S): Five women in the control group and one woman in the PCOS group were found to be affected by the LHbeta gene mutations. No difference was observed in serum androgen and E2 levels between the affected women and 25 healthy women who were homozygous for the wild-type LH. However, women whose serum LH levels were < or = 5.1 mIU/mL had a higher risk of having mutant LH. CONCLUSION(S): The frequency of LH mutations in women with PCOS is similar to that in healthy women. The presence of the variant does not cause any significant change in serum levels of androgens and E2.

Changes in bone mineral density with age, menopausal status and body mass index in Turkish women.

OBJECTIVE: The aim was to evaluate changes in bone mineral density (BMD) with age and body mass index (BMI) in healthy pre- and postmenopausal women living in the urban areas of Turkey. DESIGN: The study was prospective, carried out from 1993 to 1997. SETTING: The study carried out at a university hospital, the Istanbul University Cerrahpasa School of Medicine, Turkey. PATIENTS: The study group consisted of 849 healthy women of ages 20-84 years, admitted to the Istanbul University Cerrahpasa School of Medicine. The cases were divided into age groups, starting with 20-29 years and ending with 70 years and over. For regression analysis, the cases were further regrouped as 20-39, 40-59 and 60 years and over. Dual energy X-ray absorptiometry (DEXA) was used to measure BMD in the lumbar vertebrae (L2-L4) and in the classical locations of the proximal femur such as the femoral neck, the Ward's triangle and the trochanter. Multiple regression analysis was performed for the evaluation of annual changes in BMD with respect to age and/or BMI. RESULTS: A significant decrease in BMD started especially in the 40-49 age group, matching the average age of menopause in the study population. In contrast to the non-significant changes in the 20-39 age group, a significant decrease in BMD in the 40-59 age group, which included the average age of menopause, was detected in all locations (p < 0.0001). In addition to the significant effect of the menopause on BMD, an association between BMD and BMI was found in every location and age group (p = 0.02 to p < 0.0001). The total bone loss in the 70 and over age group, in comparison with the 30-39 age group, was 18.78% in L2-L4, 21.69% in the femoral neck, 32.68% in the Ward's triangle and 14.11% in the trochanter. Corresponding values between age groups 70 and over and 60-69 were 0.25%, 7.62%, 11.94% and 8.29%, respectively. Women in the older age groups had a slower decline in BMD in the lumbar vertebrae, in comparison with the proximal femur. Moreover, the maximum postmenopausal total bone mineral loss was in the Ward's triangle. CONCLUSIONS: The present results, confirming the results of other studies, have revealed a significant association between BMD and the menopausal status of women in the Turkish population. Additionally, a significant correlation has been detected between BMI and BMD, regardless of location and age.

Adrenal androgenic response to 2-hour ACTH stimulation test in women with PCOS.

Adrenal function may be abnormal in women with polycystic ovary syndrome (PCOS). This study aims to evaluate adrenal steroid response to the adrenocorticotropic hormone (ACTH) stimulation test and to find out the effect of high serum testosterone levels on adrenal response. We have also investigated any subtle enzyme deficiency by extending blood sampling to 2 h with 30 min intervals following ACTH administration. Twenty-eight women with PCOS and 18 healthy controls without hirsutism and oligomenorrhea were included in the study. After determining their serum basal levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone, dehydroepiandrosterone sulfate (DHEAS), 17-hydroxyprogesterone (17-OHP), and progesterone, ACTH stimulation test was performed. The change in serum 17-OHP and the summed rate of change in serum 17-OHP and progesterone levels were estimated and 95th percentile for each value was computed. Women with PCOS were heavier and more hirsute than controls (p < 0.01, p < 0.001, respectively). Serum basal LH, LH:FSH ratio, testosterone (p < 0.001, for all), DHEAS (p < 0.01), and 17-OHP (p < 0.05) were higher in women with PCOS. All of the 17-OHP measurements, including basal and each 30 min interval after the administration of ACTH, were higher in women with PCOS than those of healthy controls (p < 0.05, p < 0.002, p < 0.001, p < 0.015, p < 0.018, respectively). However, the incremental changes in serum 17-OHP30-0, 17-OHP60-0, 17-OHP90-0, 17-OHP120-0, and the summed rate of change in serum 17-OHP and progesterone in women with PCOS were not different from those in healthy controls. The incremental response in terms of serum progesterone, DHEAS, and testosterone levels to the ACTH stimulation test for each 30 min interval was not different in women with PCOS than in healthy controls. We were not able to show any critical value for serum basal testosterone and DHEAS levels that would effect response to ACTH stimulation in terms of 17-OHP levels. We have concluded that extending the duration of blood sampling up to 2 h has no advantage in evaluating adrenal steroid response to ACTH stimulation. Since serum 17-OHP levels remain within normal limits in response to ACTH stimulation, the origin of elevated serum basal 17-OHP levels may be polycystic ovaries. Elevated serum testosterone level does not have any adverse effect on adrenal function. Serum progesterone measurement seems to have no place in the diagnosis of 21-hydroxylase deficiency. Adrenal androgenic response to ACTH stimulation is normal in women with PCOS.

Mammographic changes in women receiving tibolone therapy.

OBJECTIVE: To investigate the effects of tibolone therapy for menopausal symptoms on mammographic findings and to identify any association between mammographic changes and the demographic and hormonal characteristics of women receiving tibolone. DESIGN: A prospective study. SETTING: A university hospital. PATIENT(S): Seventy-five women who were in the climacteric or postmenopausal period were recruited, and 25 of them were followed up for 24 months. INTERVENTION(S): After high-resolution mammographies were performed and blood samples were collected, tibolone (2.5 mg/d) was administered orally to all patients. At the end of the 24-month follow-up period, blood samples were collected again and mammographies were repeated. MAIN OUTCOME MEASURE(S): Serum levels of LH, FSH, prolactin, estradiol, testosterone, and DHEAS were determined from the collected samples, and mammographies were interpreted. RESULT(S): At the end of the 24-month follow-up period, mammographic changes were observed in only two women (8%). Women who had no change in mammography constituted group I (n = 23). Women who had a change constituted group II (n = 2). Although the initial hormone levels were not different, the increase in serum DHEAS in group I was significantly higher than in group II (z = 2.30, P = 0.021). CONCLUSION(S): The frequency of mammographic changes in women receiving tibolone therapy was found to be 8% at the end of the 24-month follow-up. The serum DHEAS level may be an important hormonal marker complementary to mammographic screening for women receiving tibolone therapy. We strongly believe that tibolone is safe in terms of mammographic changes in postmenopausal women.

Antibiotic therapy in men with leukocytospermia.

OBJECTIVE: In this prospective study, we aimed to determine the efficacy of doxycycline and doxycycline plus ceftriaxone for the treatment of asymptomatic men with leukocytospermia. METHOD: Seventy men were included in this randomized and placebo-controlled study. White blood cell (WBC) concentrations were determined by peroxidase assay during the routine semen analysis. Twenty-four of 70 men with leukocytospermia were randomized as control group and administered placebo (group I), 25 received doxycyline alone (group II), and 21, doxycycline plus ceftriaxone (group III). Doxycycline, 100 mg, was given twice a day for ten days and ceftriaxone, 1 g, in two doses for only one day. After the treatment, semen analyses were repeated. RESULTS: After the treatment there was a significant decrease in WBC counts in groups II and III when compared with group I (P < .05). Both antibiotic regimens were found to be equally effective. However, the time needed for resolution of leukocytospermia (approximately 4 weeks) was similar between the control and treatment groups. CONCLUSION: Although both antibiotic regimens significantly, and equally, improved the white blood cell counts in men with leukocytospermia, they failed to treat the leukocytospermia, i.e., to bring the count below the limit of one million WBC/mL. Therefore, it is doubtful that antibiotic therapy should be recommended for asymptomatic men with leukocytospermia.

Mammographic changes in women on hormonal replacement therapy.

OBJECTIVES: In the present retrospective study, we aimed to determine the frequency and the types of mammographic changes of breast parenchyma in women receiving hormone replacement therapy (HRT). We also investigated whether there was an association between mammographic changes and some clinical and hormonal characteristics of the women on HRT. METHODS: One-hundred and eight women were included into the study. Of the 108 women, 19 were climacteric, four premature menopause, 50 spontaneous menopause and 35 surgical menopause. Prior to the start of HRT, an initial mammography was performed and it was repeated at 6- to 18-month intervals according to the women's status. Estrogen alone was started for 35 surgical menopause women and a combination of estrogen plus progesterone for the remaining 73 women. RESULTS: Group I consisted of 96 women with no parenchymal changes or a decrease in parenchymal density on mammography, whereas group II consisted of 12 women with an increase in parenchymal density (11%) during the mean period of 24 months. Endogenous E2 levels were significantly higher in group II than in group I (52.4 +/- 42.3 pg/ml vs. 32.3 +/- 29.3 pg/ml, P < 0.05). Climacterium or types of menopause did not affect the mammographical density changes. Neither the type nor the duration of HRT had an effect on mammographic density increase. CONCLUSIONS: We concluded that the endogenous E2 level might be an important role in screening the women mammographically. Long-term follow-up studies were concluded to be needed in order to evaluate the effects of HRT on mammographic changes.

Effects of indoleamines on sperm motility in vitro.

Indoleamines are products of the pineal gland and are postulated to play an antigonadotrophic role in the reproductive system of mammals. In humans, indoleamines have been localized in tissue fluids such as plasma, serum and cerebrospinal fluid. Because indoleamines exhibit antigonadotrophic properties, the authors examined whether these agents cause inhibitory effects on sperm motility. In this study, time and dose-dependent inhibition of sperm motility by indoleamines was observed. Furthermore, the presence of indoles in incubation medium decreased sperm velocity. These data suggest that the presence of high doses of indoles in reproductive fluids may inhibit sperm motility and velocity.

[Anti-prostaglandins in therapy for side effects of intrauterine contraceptive devices]. / Rahim ici kontraseptif araclarin yan etkilerinin tedavisinde anti-prostaglandinler.

PIP: 43 women aged 21-35 with 0-4 parity wearing Lippes Loop IUD were studied in a double-blind trail during 3 menstrual cycles to find out if proquazon, a prostaglandin (PG) synthesis inhibitor, prevented the adverse effects of the IUD. IUDs increase the PG level in the endometrium. Higher PG levels result in pain through uterine cramping and endometrial bleeding caused by increased vascular permeability (70- 10-0 ml. blood loss vs. the normal amount of 35 ml). 200 mg of proquazon was administered 3/day (t.i.d.) for 79 cycles and 1 capsule of placebo was given for 50 cycles. Proquazon mitigated pain and reduced the incidence of severe pain: pain was absent in 33 (42% cycles with proquazon vs. 7 (14%) with placebo; light pain occurred in 29 (37%) vs. 15 (30%) respectively; medium strong pain occurred in 12 (15%) vs. 17 (34%), respectively; and severe pain was observed in 5 (6.3%) vs. 11 (22%), respectively.^ieng

Hepatic cirrhosis and hepatic ultrastructure in pregnancy.

Hepatic cirrhosis rarely occurs with pregnancy. Since no report has been made on hepatic cirrhosis and hepatic ultrastructure in pregnancy, we present a case of cirrhosis and pregnancy in which a study of hepatic ultrastructure was carried out.