Ozgul Muneyyirci-Delale

Menstrual function in human immunodeficiency virus-infected women without acquired immunodeficiency syndrome

To assess whether HIV infection is associated with menstrual abnormalities in HIV-infected women without AIDS, we evaluated 248 premenopausal HIV-infected women without AIDS and 82 HIV-negative women. Detailed medical, drug use, and menstrual histories (using menstrual calendars) were obtained. Complete physical and pelvic examinations and CD4 counts were performed. HIV-infected women were more likely to experience intervals > 6 weeks without menstrual bleeding [8 vs. 0%, odds ratio (OR) = 10.8, 95% confidence interval (CI) 1.8-1,000) and amenorrhea > 3 months (5 vs. 0%, OR = 7.1, 95% CI 1.1-1,000) (after adjustment for drug use, age, and race). Premenstrual breast swelling (p = 0.01), tenderness (p = 0.01), and dysmenorrhea (p = 0.04) were less common in HIV-infected women. There were no differences in intermenstrual bleeding or irregular menstrual cycles. Among HIV-infected women, only a past history of substance abuse was significantly associated with menstrual irregularities in a logistic regression model adjusting for age, current and past drug use, alcohol use, cigarette smoking, CD4 count, and category B conditions [1993 Centers for Disease Control (CDC) classification system]. The increase in amenorrhea (> 3 months) and in menstrual cycle intervals > 6 weeks and the lower rates of premenstrual breast symptoms in HIV-positive women suggest the possibility of disturbances in menstrual function that do not appear to be attributable to clinically apparent secondary complications of HIV. Changes in menstrual function were also significantly associated with a past history of, but not current, substance abuse, suggesting the possibility that socioeconomic factors rather than biologic effects of drugs may be responsible.

Placental 11β-hydroxysteroid dehydrogenase activity in normotensive and pre-eclamptic pregnancies

Apparent mineralocorticoid excess and licorice induced hypertension, both hypertensive disorders, have been attributed to a defect in the enzyme 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD), which interconverts cortisol to cortisone. Therefore, we undertook this study to determine the role of human placental 11 beta-HSD activity in preeclampsia, which is a hypertensive disorder in pregnancy. 11 beta-HSD activities were determined in placentas of 17 normotensive and 11 preeclamptic patients matched for gestational age at 34-42 weeks. Cortisol levels in umbilical venous and arterial sera were also determined for both groups. Statistical analysis was performed using Students t-test, significance at p < 0.05. 11 beta-dehydrogenase (oxidation activity of 11 beta-HSD) activity was significantly lower in placentas of preeclamptic compared to normotensive patients (0.19 +/- 0.09 vs. 0.26 +/- 0.08 mmoles/min/placenta, p = 0.02). Cortisol level in umbilical cord blood was significantly higher in the preeclamptic group (14.99 +/- 14.08 vs. 6.71 +/- 3.69 g/dL, p = 0.02). The decreased 11 beta-HSD activity is accompanied by an expected increase in umbilical cord blood cortisol level and decrease in fetal weight. This enzyme may play an important role in influencing fetal growth.

Serum ionized magnesium and calcium in women after menopause: inverse relation of estrogen with ionized magnesium

OBJECTIVE To study the serum concentrations of the sex steroid hormones and free divalent cations Mg2+ and Ca2+ in healthy women at or past menopause and to compare them with the serum concentrations of healthy, cycling women of child-bearing age at different stages of the menstrual cycle. DESIGN Controlled clinical study. SETTING An academic medical center. PATIENT(S) Women of varying age and duration of menopause, and healthy, cycling women. INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) Serum levels of the sex steroids (estrogen, progesterone, and testosterone) and of Ca2+ and Mg2+ were measured in menopausal and postmenopausal women, and in healthy, cycling women at five different stages of the menstrual cycle. RESULT(S) The Mg2+ and total Mg levels of the postmenopausal women were inversely related to the serum level of estrogen and were similar to the levels present during the early follicular phase of healthy women of child-bearing age. The Ca2+ level was unrelated to the sex steroid hormones present, but it was increased compared with that of younger women in both the follicular phase and the luteal phase. CONCLUSION(S) Serum levels of Mg2+ and total Mg were inversely correlated with the estrogen concentration in menopausal women. Serum levels of Ca2+ were significantly elevated in menopausal women compared with younger women, but the ratio of Ca2+ to Mg2+, a measure of cardiovascular problems, was not elevated in the postmenopausal women.

Reproductive BiologySex Steroid Hormones Modulate Serum Ionized Magnesium and Calcium Levels Throughout the Menstrual Cycle in Women 1

OBJECTIVE To determine the serum concentrations of the sex steroid hormones with respect to the concentrations of the biologically active fractions of magnesium and calcium during the different phases of the menstrual cycle. DESIGN Controlled clinical study. SETTING An academic research environment. PATIENT(S) Six parous and four nulliparous healthy cycling female volunteers. MAIN OUTCOME MEASURE(S) Concentrations of the sex steroid hormones estrogen, progesterone, and testosterone as well as the ionized Ca and Mg levels were measured in the serum of normal cycling women during five different stages: the menstrual, early follicular, late follicular, ovulatory (ovulatory/early luteal), and luteal phases. RESULT(S) In each woman, there was a comparatively high ionized Mg level coincident with the early follicular phase, a statistically significant decrease in ionized Mg around the time of ovulation, a significant decrease in ionized and total Mg when the serum progesterone concentration peaked, and a significant increase in the serum Ca2+/Mg2+ ratio at both the ovulatory and luteal phases. In addition, a decrease in ionized Mg was found with increased testosterone levels. CONCLUSION(S) Healthy women of reproductive age demonstrate recurring cycling of ionized Mg and cyclic alterations in the ionized Ca to Mg ratio in their serum. The changes in serum concentrations of these important physiologically active cations, in the range at which they occur, can affect such entities as the vasculature, synaptic transmission, and excitation-secretion coupling and thus can produce the well-known premenstrual syndromes during the luteal phase in women who are somewhat deficient in Mg or in those who have an unusually increased Ca2+/Mg2+ ratio.

Divalent cations in women with PCOS: implications for cardiovascular disease

Polycystic ovary syndrome (PCOS) patients are known to have a high incidence of insulin resistance and glucose intolerance and tend to be at eventual high risk of hypertension ,diabetes mellitus and cardiovascular disease. It has been repeatedly shown that a low serum ionized magnesium (Mg2+) and a high ionized calcium to magnesium (Ca2+/Mg2+) ratio is often associated with insulin resistance ,cardiovascular problems ,diabetes mellitus and hypertension. We were therefore interested in assessing the serum divalent cation profile of PCOS patients compared with that of normal women of similar age. We found significantly lower serum Mg2+ and total magnesium and a significantly higher serum Ca2+/Mg2+ ratio in the PCOS patients compared with the controls. No correlation was found ,however ,between the serum concentrations of steroid hormones (estrogen ,progesterone and testosterone) ,or any of the cations in the PCOS patients or the controls.

Medical management of recurrent endometrioma with long-term norethindrone acetate.

Purpose Evaluate the efficacy of norethindrone acetate in the resolution of symptoms and regression of recurrent endometrioma. Patients and methods Retrospective chart review at SUNY Downstate Medical Center of patients with a history of surgical excision of endometrioma (with histological confirmation) and recurrent endometrioma (demonstrated by strict sonographic criterion of endometrioma) who were willing to undergo follow-up. Patients were prescribed norethindrone acetate to be taken daily with follow-up sonograms until cysts regressed. Statistical analysis included Student’s t-test and a simple linear regression model to assess cyst regression over time during treatment. Results Degree of pain was significantly lower on treatment when compared to baseline (P < 0.00001). Cyst size was significantly smaller in as little as 3 months (P < 0.0001). Average rate of regression with continuous treatment was 0.025 ± 0.015 cm/day. Total mean ± standard deviation regression time is 10.28 ± 8.25 months. Conclusion Norethindrone acetate was effective in eradicating symptoms and producing complete regression of recurrent endometriomas. It should be considered for patients who are likely to adhere to a prolonged treatment regimen and comply with recommendations for surveillance with serial sonograms.

Serum ionized magnesium and calcium and sex hormones in healthy young men: importance of serum progesterone level.

OBJECTIVE To determine the serum concentrations of the sex hormones with respect to the concentrations of the biologically active fractions of magnesium (Mg) and calcium (Ca) in healthy young men and to compare them with those in young and older women. DESIGN Controlled clinical study. SETTING An academic research environment. PATIENT(S) Twenty-five healthy young male volunteers. INTERVENTION(S) None. MAIN OUTCOME MEASURE(S) Concentrations of the sex steroid hormones testosterone, estrogen, and progesterone, and levels of ionized Ca (Ca2+) and Mg (Mg2+) were measured in the serum of healthy young men. These levels were compared with those in young women at different phases of the menstrual cycle and with those in older women. RESULT(S) The Mg2+ and total Mg concentrations in young men were not different from those during the follicular phase in young women or from the mean concentrations in menopausal women. The Ca2+ levels in young men were similar to the levels in young women during the follicular phase but significantly lower than the levels in older women. The Mg2+ concentration in the young men was directly and significantly related to the progesterone level, and the Ca2+/Mg2+ ratio was inversely related to the progesterone level. CONCLUSION(S) Progesterone may be a more important steroid hormone in men than previously believed.

Presence of 11β-hydroxysteroid dehydrogenase in human semen: Evidence of correlation with semen characteristics

11 beta-hydroxysteroid dehydrogenase (11 beta-HSD), the enzyme that catalyzes the conversion of biologically active glucocorticoids to their inactive metabolites, was shown to be located exclusively in Leydig cells of the rat testis, and its appearance was associated with the developmental rise in testosterone. Thus, 11 beta-HSD was suggested to play an important role in maintaining steroidogenesis by inactivating excess cortisol that inhibits testosterone production. Whether equivalent protection from glucocorticoids excess is necessary for spermatogenesis is not known, and we have, accordingly, investigated the 11 beta-HSD activity in ejaculated human semen. Both 11 beta-dehydrogenase (11 beta-DH) and 11 beta-oxoreductase (11-OR) activities of 11 beta-HSD were measurable in semen, although seminal plasma was devoid of 11 beta-HSD activity. Azoospermic specimens were associated with low 11 beta-dehydrogenase activity, indicating the presence of enzyme activity in cells other than spermatozoa. Pure spermatozoa separated on percoll gradient could oxidize corticosterone in the presence of NAD or NADP. Significantly higher 11 beta-DH activity is associated with semen specimens with low sperm count (p < .05) and higher level of morphologically abnormal spermatozoa (p < .05). The presence of 11 beta-HSD in human semen and its association with sperm characteristics thus suggests functional role for glucocorticoid exclusion in the sperm maturation process.

11β‐Hydroxysteroid Dehydrogenase Inhibitor Carbenoxolone Stimulates Chorionic Gonadotropin Secretion from Human Term Cytotrophoblast Cells Differentiated In Vitro*

Problem:  To investigate the effect of altering local glucocorticoid concentration on human chorionic gonadotropin (hCG) production by cultured placental trophoblast cells.

Circulating Divalent Cations in Asymptomatic Ovarian Hyperstimulation and in vitro Fertilization Patients

It is known that ovarian hyperstimulation and in vitro fertilization are accompanied by a steady increase in circulating estrogen and progesterone far beyond what is normal for young women. We have recently demonstrated that the biologically active fractions of calcium and magnesium in blood are altered depending on when in the menstrual phase a blood sample is drawn in normal cycling women. The serum ionized Ca/Mg ratio is also altered in accordance with the menstrual cycles. This suggests that the sex steroid hormones may modulate serum levels of ionized Mg and the ionized Ca/Mg ratio. We therefore studied the relationships between sex steroid hormones and the concentrations of ionized magnesium and calcium in the blood of hyperstimulated patients. We were able to demonstrate that with each increment in estrogen, a decrease in ionized Mg occurred, and as the progesterone rose in the blood, the ionized Ca/Mg ratio increased. Our results support the idea that serum estrogen and progesterone levels in women modulate the blood levels of circulating ionized Mg and the serum ionized Ca/Mg ratio.