Organization and results of an in vitro fertilization program at the Huddinge University Hospital are given from its beginning in August 1985: 6 months in advance a scheme is scheduled with 2 weeks open for treatment followed by free intervals of 3-4 weeks. Follicular development is stimulated with clomiphene citrate and hMG, and assessed by analyses of estradiol and LH in serum combined with ultrasound examinations. Following the administration of hCG, eggs are collected by transvesical aspiration guided by ultrasound. The ova are inseminated with about 50,000 motile spermatozoa, and cultured for 48 h. Up to four eggs are transferred transcervically to the uterine cavity. 158 egg pickups have been performed (August 1985 to December 1987) in 106 patients resulting in fourteen intrauterine and two ectopic pregnancies, biochemical pregnancies not counted. This protocol has restricted routine work load allowing these treatments to be part of the clinical routine. It has also allowed the application of research programs and thus optimized limited resources.
Serum concentrations of dehydroepiandrosterone sulphate (DHAS) were determined in 590 healthy women aged 20–87 yr. Simultaneous assays of dehydroepiandrosterone (DHA) were performed in 417 of the women. DHA and DHAS levels correlated negatively with age while the DHA/DHAS ratio proved to be unrelated to age. When values for 60 healthy men in the age range 20–84 yr were compared with those obtained in 60 randomly-selected healthy women who were exactly age-matched, the DHAS levels were found to be significantly lower and the DHA/DHAS ratios significantly higher in the women. These results might be of use in establishing normal clinical ranges for serum DHA, DHAS and the DHA/DHAS ratio in women.
Basal levels and ACTH-induced increments of serum 17 alpha-hydroxyprogesterone (170HP), cortisol, 4-androstene-3,17-dione (A-4), dehydroepiandrosterone (DHA), and dehydroepiandrosterone sulphate (DHAS) were related to the degree of obesity and to trabecular bone mineral density in 29 postmenopausal women. The ACTH-induced increment of 170HP (delta 170HP) was negatively correlated to basal DHA and delta DHA. Positive correlations were found between obesity, expressed as Broca's index, and delta DHA and the delta DHA/delta 170HP ratio. Bone mineral density was positively correlated to basal DHAS, delta DHA, delta DHAS and the delta DHA/delta 170HP ratio, and negatively correlated to delta 170HP. DHA and 170HP represent a crossroad in adrenocortical steroid biosynthesis, leading to delta 5-androgens and glucocorticoids as main products. Besides age, obesity may also influence the intra-adrenal distribution between these two main steroidogenic pathways. The results suggest that differences at a very early stage of the adrenal steroidogenesis may influence calcium homeostasis in the post-menopausal woman.
Serum levels of sex hormone binding globulin (SHBG) and testosterone (T) and bone mineral density (BMC) in the non‐dominant forearm were determined in 28 postmenopausal women aged 44‐62 years. Significant correlations (Spearman's rank correlation test) were found between BMC and SHBG (negative) and between BMC and the T/SHBG index on biologically active androgen (positive). Significant correlations were also found between endometrial pathology (Kruskal‐Wallis test; 0 = atrophic, 1 = hyperplasia, 2 = cancer) and SHBG (negative) and the T/SHBG index (positive). It is suggested that SHBG may act as one common denominator in the pathogenesis of postmenopausal osteoporosis and endometrial disease by regulating the levels of unbound, biologically active androgens and estrogens.
A 10-year follow-up (1970-79) of a defined general population (n = 159 200) of middle-aged (born in 1911-40), urban, native Swedes, revealed that the prevalence rate of subarachnoid hemorrhage was 2.8 times higher in females than in males. This was mainly due to an accumulation of non-hypertensive aneurysmal subarachnoid bleeds in women born in the period 1932-40. The cases were significantly (P less than 0.001) overrepresented among divorced women, with relative risks of 1.89, 0.98 and 0.63 for divorced women, married women and spinsters (never married), respectively. Since high-dose estrogen-progestagen oral contraceptives have largely been used by the younger members of this study cohort, it may be speculated whether the observed substantial excess prevalence rate of subarachnoid hemorrhage with saccular aneurysm, not reported previously, represents a cohort effect unexpected after the introduction of low-dose oral contraceptives.
A radioimmunoassay for serum 4-androstene-3,17-dione (A-4) using anti-4-androstene-3, 17-dione-11 alpha-hemisuccinate bovine serum albumin was applied to serum samples from 16 healthy, normally menstruating women in different phases of the menstrual cycle, from 36 healthy postmenopausal women and from 23 postmenopausal women with various bone mineral contents and endometrial conditions, undergoing an acute ACTH stimulation test. The values obtained in the normal subjects were consistent with those found in the literature. A-4 levels were significantly higher at midcycle than in the follicular phase and were significantly lower in postmenopausal than in menstruating women. ACTH increased the levels of A-4 significantly. However, no significant correlation was found between basal levels or the ACTH-induced increments of A-4 on the one hand and bone mineral content, endometrial condition and the patients' weight, age, or Broca's index on the other. This is in contrast to our previous finding of significant correlations between basal dehydroepiandrosterone sulfate and ACTH-induced increments in dehydroepiandrosterone on the one hand and bone mineral content on the other in the same clinical material. We discuss whether the differences in correlations to bone mineral content between the two adrenocortical androgens may be due to a rather more complex origin of the steroid moiety of A-4.
Thirteen postmenopausal women with benign endometrial changes including proliferative, secretory and polypous endometrium, endometrial hyperplasia and atypia (group I) and 13 randomly selected age-matched controls with normal atrophic endometrium (group II) were studied with respect to serum levels of dehydroepiandrosterone (DHA) and its sulfate (DHAS), testosterone, total estrone, estradiol-17 beta, progesterone, FSH and prolactin. Serum levels of DHA, DHAS, testosterone and total estrone were significantly higher in group I than in group II; otherwise no significant differences were found. Mean values for body weight and for Broca's index, respectively, were almost identical in the two groups. It is speculated that the adrenal androgens may affect the endometrium in two ways, viz. via peripheral conversion to estrogens and/or via direct interaction with endometrial steroid receptors. The results give further support to the hypothesis of an association between adrenocortical hyperactivity and endometrial abnormalities including endometrial carcinoma.
In 23 post-menopausal women, serum levels of cortisol, unconjugated dehydroepiandrosterone (DHA), dehydroepiandrosterone sulphate (DHAS), testosterone, unconjugated and total oestrone and prolactin were measured before and during an ACTH test. Significant positive correlations were found between basal levels of DHA and DHAS; DHA and unconjugated oestrone; DHA and total oestrone; testosterone and total oestrone and between unconjugated and total oestrone. ACTH significantly raised the levels of the steroids but not of prolactin. Significant positive correlations were found between basal levels and ACTH induced increments in DHA; between basal DHAS and increments in DHA and between increments in DHA and DHAS. A significant negative correlation was found between basal levels and increments in cortisol. No significant correlations were found between other combinations of hormone basal levels and/or increments. Significant positive correlations were found between basal levels of DHAS and the DHA response to ACTH respectively, and trabecular bone mineral content of the distal forearm. A significant correlation was also found between bone mineral content and pre-cancerous/ cancerous state of the uterine epithelium.
In 19 postmenopausal women, basal serum levels of cortisol, unconjugated dehydroepiandrosterone (DHA), dehydroepiandrosterone sulphate (DHAS), testosterone and unconjugated and total estrone were measured both before and during an ACTH test. A positive correlation was found both between basal levels of DHAS and the DHA response to ACTH, respectively, and trabecular bone mineral content of the distal forearm. A significant correlation was also observed between bone mineral content and precancerous/cancerous states of the uterine epithelium.