A. Lagrelius

Premature Rupture of the Membranes

The etiology of premature rupture of the membranes (PROM) has been investigated in 30 consecutive cases and 30 matched controls. The significance of several possible factors predisposing to this condition is discussed and the obstetric and pediatric outcome reviewed. Significantly increased frequencies of previous genital operations, cervical operations and lacerations were found in the PROM group, which also contained significantly more heavy smokers. The relation between the length of the PROM delivery time interval and the risks of prematurity and infection are discussed. Patients delivered > 24 hours after PROM had significantly more puerperal infections than those with a latent period of > 24 hours. Maternal fever was found to be an unreliable prognostic indicator. The incidence of puerperal infection amounted to 27 per cent in the PROM group. A 12 per cent incidence of proven neonatal septicaemia contributed to a high perinatal mortality rate (17.6 per cent).

Adrenocortical steroids, bone mineral content and endometrial condition in post-menopausal women

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. The results are a further support to the concept of a link between adrenal androgens and bone mineral density, and do also indicate a relation to endometrial pathology. The lack of correlation between cortisol and other steroids indicate different regulatory mechanisms. Prolactin does not seem to be involved in the regulation of the adrenal androgen synthesis.

Relative Fatty Acid Composition of Lecithin during Postmenopausal Replacement Therapy – A Comparison between Ethinyl Estradiol and Estradiol Valerate

The relative fatty acid composition of serum lecithin was followed in groups of women during postmenopausal replacement therapy. The effects of estradiol valerate and ethinyl estradiol in two different doses, and the modulating influence of various progestogens and antiestrogens were compared. Unopposed estrogen treatment enhanced liver lecithin synthesis along pathway I, i.e. reduced the amount of stearic acid and increased the amount of palmitic acid. The effect was clearly dose-dependent and even the low dose of 10 micrograms of ethinyl estradiol was more potent than 2 mg of estradiol valerate. No qualitative difference between the two estrogens was recorded. The sequential addition of the antiestrogen tamoxifen significantly reduced the influence of ethinyl estradiol. Liver lecithin synthesis along pathway I may be stimulated by all estrogens and not only by 17C-alkylated compounds. The prostaglandin precursors, dihomogammalinolenic and arachidonic acid, showed a seemingly dose-dependent increase during estrogen treatment. The comparatively weaker effects of estradiol valerate on lipid metabolism should make this non-alkylated estrogen the first choice in clinical practice.

Adrenal steroids in post-menopausal women: Relation to obesity and to bone mineral content

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 Brocas 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 Sex Hormone Binding Globulin (SHBG), Testosterone/SHBG Index, Endometrial Pathology and Bone Mineral Density in Postmenopausal Women

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 (Spearmans 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.

Is there an altered steroid profile in patients with endometrial carcinoma

Background. Besides the well‐known association between endometrial carcinoma (EC) and unopposed estrogen, androgens also may play a role in this respect; however, previous studies on endogenous estrogens and androgens in patients with EC and control subjects have yielded mostly divergent results, probably because of the use of poorly defined control groups.

Treatment with Oral Estrone Sulphate in the Female Climacteric

Abstract. Thirty‐eight women were treated with estrone sulphate over a period of 30 months for climacteric problems. A random control group of 29 women were given methyl scopolamine.

ADRENAL STEROIDS, BONE MINERAL CONTENT AND ENDOMETRIAL PATHOLOGY IN POSTMENOPAUSAL WOMEN

Abstract. 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.

Clinical Experience with a Low‐Dose Combination of Estradiol Valerate and Levonorgestrel: Double‐blind Comparative Study between SH D 386 F and Cyclabil. Effects on Symptoms, Lipids and Endometrial Condition*

In a double blind study of the effects of hormone replacement therapy in climacteric women, two different dosages of estradiol—17β valerate and levonorgestrel, with the same ratio between the amounts of the two steroids (Cyclabil and the trial preparation having the code number SH D 386 F respectively), were compared. The differences in effects on symptoms, certain humoral parameters including serum lipids, and endometrial histology before and after 12 months of therapy were evaluated.

SERUM LEVELS OF DEHYDROEPIANDROSTERONE SULPHATE AND TOTAL ESTRONE IN POSTMENOPAUSAL WOMEN WITH SPECIAL REGARD TO ‘NON‐ENDOCRINE’ OVARIAN CARCINOMA

Abstract. Postmenopausal women with ‘non‐endocrine’ ovarian cancer have previously been reported to have elevated levels of estrogens, androstenedione and progesterone (1, 2, 3, 4). A contribution from the tumor‐affected ovary to the elevated steroid levels seems evident (1, 4), though the underlying mechanisms are obscure. After the menopause estrogens are normally formed by peripheral conversion of adrenal androgens, and ovarian function is of little significance. Tuimala et al (2) suggested conversion of adrenal precursors by the tumor tissue as an alternative explanation for the elevated estrogen levels in postmenopausal women with ovarian cancer. If this is so, the levels of adrenal androgens may be important. The weak androgen dehydroepiandrosterone sulphate (DHAS) is of an exclusive adrenal origin and is considered to be the best indicator of adrenal androgen secretion. In order to study a possible relationship between adrenal activity and postmenopausal ‘non‐endocrine’ ovarian cancer, we determined the peripheral serum levels of DHAS and total estrone in postmenopausal women with this disease and in strictly age‐matched healthy controls.