Snezana Micic

Serum sex hormones and endurance performance after a lacto-ovo vegetarian and a mixed diet

Serum sex hormones and endurance performance after a lacto-ovo vegetarian and a mixed diet. Med. Sci. Sports Exerc., Vol. 24, No. 11, pp. 1290-1297, 1992. The effect of a lacto-ovo vegetarian (V) and a mixed, meat-rich (M) diet on the level of serum sex hormones, gonadotropins, and endurance performance of eight male endurance athletes was investigated in a 2 x 6 wk cross-over study. The energy contribution from carbohydrate, fat, and protein was 58%, 27%, and 15% on the V diet and 58%, 28%, and 14 E% on the M diet. For total fasting serum testosterone (T) there was a significant interaction between diet and time (P < 0.01). Thus, the V diet resulted in a lower total T level (13.7, 9.8-32.4 nmol.l-1) (median and range) compared with the M diet (17.4, 11.8-33.5 nmol.l-1). During exercise after 6 wk on the diets total T was also significantly lower on the V than on the M diet (P < 0.05). Serum free testosterone, however, did not differ significantly during the 6 wk dietary intervention periods and neither did serum concentrations of sex hormone binding globulin, dihydrotestosterone, dehydroepiandrosterone sulphate, 4-androstenedione, estrone, estradiol, estrone sulphate, or gonadotropins. Endurance performance time was higher for six and lower for two after the mixed diet compared with the vegetarian diet. This was not significant, however. In conclusion, 6 wk on a lacto-ovo vegetarian diet caused a minor decrease in total testosterone and no significant changes in physical performance in male endurance athletes compared with 6 wk on a mixed, meatrich diet.

Hormonal and menstrual changes after laparoscopic sterilization by Falope-rings or Filshie-clips.

OBJECTIVE To evaluate the influence of laparoscopic sterilization by Falope-rings (Cabot Medical Corp., Langhorne, PA) or Filshie-clips (Femcare, Nottingham, United Kingdom) on menstrual pattern and ovulatory function. DESIGN A prospective, nonrandomized study of women sterilized by Falope-rings (n = 6) or Filshie-clips (n = 5). Menstrual charts were kept. Serum follicle-stimulating hormone (FSH), estradiol (E2) and progesterone (P) were measured by means of radioimmunoassay in one cycle before and 3, 6, and 12 months after the sterilization. Blood samples were drawn on day -6, -2, 0, +6, +10 of the menstrual cycle, ovulation corresponding to day 0. The women sterilized by Filshie-clips had abdominal ultrasonography of the ovaries measuring the leading follicle on day -6, -2, 0, +6 of the menstrual cycle. PATIENTS Twelve women, 25 to 38 years old, with regular menstrual cycles and no use of oral contraceptives or intrauterine contraceptive device at least 6 months before sterilization. One woman was excluded. RESULTS After the sterilization, all women reported unchanged menstrual pattern. The follicular rise in E2 unchanged, and FSH levels fell accordingly. Progesterone levels were ovulatory, but the midluteal P peak 3 months poststerilization was significantly decreased. Serial abdominal ultrasonography in women sterilized by Filshie-clips confirmed ovulation in all cycles except in one woman, who had an unruptured follicle in one cycle before and in the sixth cycle after sterilization. CONCLUSION Laparoscopic sterilization by Falope-rings or Filshie-clips does not seem to interfere with menstrual pattern or ovulatory function.

Dopaminergic regulation of gonadotropin levels and pulsatility in normal women.

This study was done to define the concentration of dopamine (DA) that inhibits gonadotropin secretion and to study the effect of DA D-2 receptor blockade during the infusions. Normal women received 5-hour infusions of either glucose (n = 14) or DA at rates of 0.04 (n = 6), 0.4 (n = 6), and 4.0 micrograms/kg X minute (n = 9). After 3 hours, metoclopramide (MTC) was administered. Mean serum luteinizing hormone (LH) concentration declined during 0.4 (P less than 0.01) and 4.0 micrograms/kg X minute (P less than 0.05) infusion doses of DA. This effect of DA was not consistently (P greater than 0.05) antagonized by MTC. Six women received DA (4.0 micrograms/kg X minute) or glucose for 18 hours. After 17 hours, MTC was given. Blood samples were collected every 10 minutes during the last 8 hours. No significant effect on LH pulse frequency and pulse amplitude was observed (P greater than 0.05). A marked (P less than 0.01) rise in LH occurred after MTC administration. The authors conclude that (1) physiologic doses of DA may inhibit LH secretion with only little, if any, effect on the pulsatile release; and (2) low-affinity DA receptors responsive to DA D-2 antagonists may regulate LH secretion.

Immunoreactive inhibin-production in post-menopausal women with malignant epithelial ovarian tumors

In post-menopausal women with a malignant epithelial ovarian tumor the follicle stimulating hormone (FSH) level was found to be significantly lower compared with healthy controls. We demonstrated immunoreactive (i.r.) inhibin in 20% of controls which was elevated to 60% of women with an ovarian tumor and correlating strongly to FSH in the tumor group (P = 0.0002). Steroid hormone levels were comparable in the two groups. In women with ovarian tumors the survival time for the i.r. inhibin-producing women was found to be 4.6 years compared with 0.9 year, or 5.1 times longer than in the non-producing women (P = 0.002). The site of i.r. inhibin production in these post-menopausal women is unknown, but i.r. inhibin production by the developing ovarian tumor or by the post-menopausal ovary may be regarded as a defense mechanism against an elevated gonadotrophin level (the gonadotrophin theory) which would promote further tumor growth. The recent suggestion that the alpha subunit of inhibin is a tumor suppressor gene is consistent with these results. The serum i.r. inhibin or alpha subunit concentrations might be used as an aid to diagnosis or as a prognostic indicator of survival in women with an ovarian carcinoma.

Effect of alcohol and glucose infusion on pituitary-gonadal hormones in normal females

During 1 h, median 976 mmol ethanol in 5.5% glucose was administered i.v. to six healthy female volunteers (aged 26-37 years) in the luteal phase of the menstrual cycle. The median maximal blood ethanol concentration was median 33.5 mmol/l and serum ethanol concentrations of 2 mmol/l were reached after 8 h. Four of the women participated in a control experiment with infusion of an equal volume of glucose 5.5%. Venous blood samples were drawn 5 times during the 24-h follow up period. Serum concentrations of sex steroids and pituitary hormones decreased in both ethanol and control experiments and the results did not differ significantly. The lowest hormone concentrations were observed 1-5 h after the start of infusion. Oestradiol, oestrone and oestrone-sulphate concentrations decreased 24-46% compared to basal values. 5 alpha-dihydro-testosterone levels decreased 23-31%, androstenedione and dehydroepiandrosterone-sulphate levels decreased 6-48%, while testosterone levels did not change significantly. Prolactin concentrations were reduced by 41-51% of basal values and luteinizing hormone concentrations by 37-68% Follicle stimulating hormone levels did not change significantly. Stress factors or haemodilution are not likely explanations of the observed changes in hormone concentrations. A circadian rhythm could not explain changes in hormones of non-adrenal origin.

Menopausal age and sex hormones in postmenopausal women with alcoholic and non-alcoholic liver disease

In order to evaluate age at menopause and serum sex hormone profiles in postmenopausal women with stable chronic liver disease, six non-cirrhotic alcoholics, 13 with alcoholic cirrhosis, eight with non-alcoholic cirrhosis, and 46 healthy controls were studied. In all three groups, patients were significantly (p less than 0.05) younger at the time of natural menopause than controls. Compared to controls, non-cirrhotic alcoholic women had significantly (p less than 0.05) reduced levels of DHAS, significantly (p less than 0.05) more alcoholic cirrhotic women had detectable oestradiol concentrations, elevated concentrations of oestrone and sex hormone binding globulin (SHBG) and reduced levels of 5 alpha-dihydrotestosterone (DHT), while women with non-alcoholic cirrhosis had significantly elevated concentrations of SHBG and reduced levels of oestrone sulphate, DHT, androstenedione and dehydroepiandrosterone sulphate (DHAS) (p less than 0.05). The observed changes may be a consequence of liver disease since similar changes were observed in patients with alcoholic and non-alcoholic liver disease, but an additional effect of alcohol cannot be excluded.

The post-operative gonadotropin level in post-menopausal women with epithelial ovarian cancer

Serial estimates of the post-operative hormone levels were made in 15 women subjected to oophorectomy because of ovarian carcinoma. All women were post-menopausal. Pre-operatively, they had significantly lower follicle stimulating hormone (FSH) levels compared with an age-matched control group. Blood samples were collected after a median time of 8 months (139-378 days). After oophorectomy, significantly higher FSH values were found (P = 0.0002), whereas the luteinizing hormone (LH) values were not significantly changed. The inhibin, estradiol and progesterone values were found to be significantly lowered compared with the pre-operative sample. Total and unbound testosterone levels were significantly lower while dehydroepiandrosterone sulphate (DHEAS) and androstenedione levels were unchanged compared with the original sample and compared with controls. Most likely, estradiol and progesterone are produced by the epithelial malignant tumors, as the post-operative values are completely comparable with the primarily included healthy controls. The FSH is suppressed by inhibin and only to a minor degree by the steroid hormones as indicated by the correlation coefficients. Of great interest is the question whether inhibin production is random, or defensive, lowering the gonadotropin levels or influencing tumor growth in some hitherto unknown fashion.

Ovarian carcinoma serum markers and ovarian steroid activity — is there a link in ovarian cancer? A correlation of inhibin, tetranectin and CA-125 to ovarian activity and the gonadotropin levels

In a previous study, we have demonstrated that inhibin-production may be associated with improved survival and, also, that tetranectin (TN) is a valuable prognostic marker in ovarian epithelial cancer. We investigated the possible correlation between inhibin, tetranectin, CA-125, ovarian steroid activity and the gonadotropin levels. Preoperative serum levels of the tumor markers inhibin, tetranectin (TN) and CA-125 were measured and related to ovarian steroid function and the pituitary-gonadal axis (gonadotropin levels) in 28 postmenopausal ovarian cancer patients. The following median levels and 95% confidence limits were demonstrated for the tumor markers: Inhibin 0.4 U/l (0.2-0.9), TN 8.9 mg/l (6.8-9.2), CA-125 160 kU/l (75-687). A significant inverse correlation was demonstrated between inhibin and the gonadotropins. The Spearman correlation coefficients showed a highly significant correlation of inhibin with the examined ovarian steroid hormones except DHEAS which also has a suprarenal component. This indicates a synthesis of inhibin and the steroid hormones from the same cell compartment as known from the normal ovary and an apparently intact negative feed back mechanism. Inhibin may be produced in the normal ovary as a defense mechanism against an elevated gonadotropin level and inhibin acts by lowering the gonadotropins or by altering their biological activity. Elevated values of the tumor markers TN and CA-125 due to gonadotropin stimulation could not be demonstrated but a significant inverse correlation between TN and CA-125 was confirmed.

Immunoreactive inhibin concentration in blood tested under variable sampling conditions

The stability of immunoreactive (i.r.) inhibin in blood samples drawn and handled under different conditions and at different time intervals were studied. Ten serum and plasma samples drawn in 1994 from healthy volunteers were compared to samples collected in 1986 from 10 healthy women admitted for laparoscopic sterilization and analysed 6 years later. All samples were drawn on the twelfth day of the menstrual cycle and handled under identical clinical conditions (22 degrees C). The concentrations in the 1986 samples were similar to the Se-i.r. inhibin levels from 1994. Different clotting temperatures, repetitive freezing and thawing or hemolysis had no effects on the i.r. inhibin values, whereas non-hemolysed samples left at room temperature (22 degrees C) for 3 days were significantly lower, which might be due to a statistical type 2 error. No differences in concentration between serum and plasma i.r. inhibin were demonstrated. In conclusion, i.r. inhibin is a very stable peptide hormone in both serum and plasma if drawn and handled under normal conditions.

Effect of oestrogen and progestagen on gonadotrophins and sex hormones in oophorectomized women.

Five premenopausal women were followed with measurements of androgens, oestrogens, gonadotrophins and sex hormone binding globulin (SHBG) after ovariectomy for benign disease. After a period of 6 weeks without treatment the women were treated with oestradiol 4 mg daily for 8 weeks, oestradiol 4 mg plus norethisterone acetate (NETA) 2 mg daily for 8 weeks and finally oestradiol 4 mg daily for another 8 weeks. The levels of androgens did not change during the various periods. As usual during oral treatment oestrone and oestrone sulphate were elevated while oestradiol levels were in the pre-operative range during treatment, regardless of the addition of NETA. SHBG was elevated during oestrogen-only treatment, while addition of NETA normalized the concentration of SHBG. In the combined NETA period concentrations of free oestradiol and non-SHBG-bound oestradiol were significantly elevated, and gonadotrophins returned to premenopausal levels, in contrast to the high levels in the oestrogen-only periods. Using oral oestrogen therapy it may be preferable to add a progestagen rather than elevate the oestrogen dose. Progestagen will result in more free oestradiol and give greater relief of symptoms, but the potentially harmful effect of progestagens on blood lipids must be considered.