Erdogan Ertungealp

Role of the mutations Trp8 ⇒ Arg and Ile15 ⇒ Thr of the human luteinizing hormone β-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.

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.

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 womens 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.

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 Wards 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 Wards 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 Wards 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.

F020 The effect of tibolone on serum lipid and lipoprotein levels

We investigated the effect of tibolone and estrogen-progestin replacement therapy on serum lipid and lipoprotein levels in postmenopausal women. Ninety-five women were included into the study. Initial serum HDL-C, LDL-C, VLDL-C, total cholesterol and trigliseride levels were dete~ined. Continuous CEE and MPA to 30 women (Group I), continuous CEE and cyclic MPA to 3 1 women (Group II) and tibolone to 34 women (Group III) were administered. Six months later serum lipid and lipoprotein levels were reassessed. All groups were found to be comparable in terms of age, duration of menopause, BMI and the initial serum lipid and lipoprotein levels. When we compared group I and III, there was a signi~c~t decrease in all serum lipid and lipoprotein levels except LDL-C in group III. When we compared group II and III, we determined a significant decrease in the levels of serum VLDL-C and HDL-C in women receiving tibolone. It has shown that tibolone is an alternative to estrogen-pogestin herapy in the postmenopausal women.