[Climacteric problems in 52- and 54-year-old women in the municipality of Linköping].
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Climacteric↗
Biomedical subjects
M Hammar
Publications and source records attributed to M Hammar.
Epidemiology of the climacterium.
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Adult↗
Clonidine in the treatment of menopausal flushing. A review of clinical studies.
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Climacteric↗
In vitro metabolism of 3H-pregnenolone and 3H-progesterone by adult and prepubertal human testicular tissue before and during gonadotrophic treatment.
The in vitro conversion of tritiated pregnenolone and progesterone was studied in testicular tissue from three infertile adult males before and during 25-30 weeks of therapy with hCG alone or combined with hMG. Furthermore, the in vitro conversion of pregnenolone was studied in testicular tissue from five prepubertal boys with undescended testes, two of whom had been subjected to hCG treatment for 5 weeks. The gonadotrophic treatment appeared to augment the steroid conversion mediated by the enzymes 3 beta-hydroxysteroid dehydrogenase and 17 alpha-hydroxylase in adult as well as prepubertal testicular tissue. The conversion mediated by C17-20-lyase along the delta 4 metabolic pathway was not increased, causing a "trap" along the delta 4 metabolic pathway. The increased production of testosterone in vitro from tritiated pregnenolone, which was observed during gonadotrophic treatment, probably took place along the delta 5 metabolic pathway through the C17-20-lyase step, whereas C21 steroids converted to the delta 4 metabolic pathway were found to be "trapped" as 17 alpha-hydroxyprogesterone.
Adult↗
In vitro conversion of progesterone in the human testis at different ages, pathophysiological conditions, and during treatment with estrogens or gonadotrophic hormones.
The enzyme 17 alpha-hydroxylase catalyzes the conversion of progesterone to 17 alpha-hydroxyprogesterone in the testis and may be studied with the use of incubation of testicular tissue with [3H] progesterone in vitro. The enzyme 20 alpha-hydroxysteroid dehydrogenase catalyzes the conversion of progesterone to 20 alpha-dihydroprogesterone. These enzymes were studied in testicular tissue from 105 human males regarding the effects of aging, different pathophysiological conditions, and gonadotrophic or estrogenic treatment. 17 alpha-Hydroxylase activity was low in vitro in testicular tissue from prepubertal boys, adult men with pituitary tumors, and estrogen-treated elderly men. In nontreated elderly men and certain infertile adult men, 17 alpha-hydroxylase was more active than in the above-mentioned patient groups, albeit lower than in adolescent and adult men. Gonadotropic treatment increased the conversion mediated by 17 alpha-hydroxylase in prepubertal as well as adult testicular tissue. In conclusion, the activity of 17 alpha-hydroxylase may be influenced by gonadotrophic hormones and may be an indicator of the testicular endocrine state at the moment of biopsy. Testicular 20 alpha-hydroxysteroid dehydrogenase seems to be active during low gonadotrophic influence and might even be inhibited by gonadotrophic stimulation.
20-Hydroxysteroid Dehydrogenases↗
Climacteric symptoms in an unselected sample of Swedish women.
A questionnaire on climacteric symptoms was sent to every woman living in the city of Linköping, Sweden (120,000 inhabitants) who was born in 1928 or 1930. Of the 1246 women concerned, 1118 (90%) responded. At the time of the survey, 252 women (23%) were pre-menopausal. In the total sample, 10% had undergone hysterectomy and/or bilateral oophorectomy. The median age at natural menopause was 51 yr. Climacteric symptoms were reported by 75% of the women, the predominating complaints being sweating attacks and hot flushes. Vaginal dryness and tenderness were experienced by 30% of the post-menopausal women, the discomfort tending to become more common as the duration of the post-menopausal period lengthened. After the menopause, every third women experienced periods of depression more often than previously. Depression was positively correlated to the severity of the vasomotor symptoms. Fifty percent of the women expressed interest in receiving oestrogen treatment, although only 7% were using oestrogens at the time of the survey. This discrepancy is probably due to widespread apprehension in Swedish society - shared by the doctors - in regard to 'hormonal treatment'.
Climacteric↗
Steroid biosynthesis and Leydig cell morphology in adult unilaterally cryptorchid rats.
Unilateral cryptorchidism was induced in newborn rats and when the rats reached adult age Leydig cell morphology and steroid biosynthesis were compared in scrotal and abdominal testes. The cell profile area of abdominal Leydig cells was reduced, the cytoplasm contained an increased number of lipid droplets and the endoplasmatic reticulum was more sparse than in scrotal Leydig cells. The intratesticular concentrations of progesterone, 20 alpha-dihydroprogesterone, 17 alpha-hydroxyprogesterone and testosterone were measured both basally and after LH stimulation. The synthesis of testosterone was subnormal in the abdominal testes. The data on basal steroid concentrations suggest a block at the 17 alpha-hydroxylase level, but observations after LH stimulation suggest that earlier steps are also involved. When studied in vitro the steroid biosynthesis in abdominal testes was also disturbed. The conversion mediated by 17 alpha-hydroxylase and 17 beta-ketosteroid reductase was lower and the conversion mediated by 20 alpha-dehydrogenase was higher in the abdominal testis. The reason for the disturbed steroid biosynthesis in abdominal testes is unknown. It may be related to the increased concentration of oestradiol in abdominal testes. Other possibilities are altered paracrine influence from the damaged tubules or changes in the microcirculation of the testis.
17-alpha-Hydroxyprogesterone↗
In vitro conversion of 3H-pregnenolone by human testicular tissue from fetal age to senescence.
The in vitro conversion of pregnenolone was studied in testicular tissue specimens from 6 fetuses, 3 prepubertal boys with undescended testes, 5 normal adult men, and 12 elderly males with prostatic carcinoma. Adult testicular tissue converted pregnenolone to testosterone mainly along the delta 5 metabolic pathway. Steroid intermediates that were converted from pregnenolone to delta 4 metabolites prior to the rate limiting C17-20 lyase step were "trapped" as 17 alpha-hydroxyprogesterone. The conversion patterns in testicular tissue from fetuses were similar to those in testicular tissue from adults and elderly men. In prepubertal testicular tissue, however, a significantly lower conversion was observed, mediated by the enzymes 3 beta-hydroxysteroid dehydrogenase/isomerase and 17 alpha-hydroxylase. The conversion mediated by 17 alpha-hydroxylase was significantly lower in testicular tissue from the elderly males than from younger adults, suggesting a relative steroidogenic insufficiency in the elderly males. Testicular tissue from an anencephalic fetus produced testosterone and steroid intermediates in vitro, although to a lesser extent than in testicular tissue from other fetuses. The enzymes 3 beta-hydroxysteroid dehydrogenase/isomerase and 17 alpha-hydroxylase appeared to be under gonadotropic control.
3-Hydroxysteroid Dehydrogenases↗
Analysis of steroid conversion in vitro by testicular tissue as a means of selection of infertile males for gonadotrophic substitution therapy.
Testicular biopsy specimens from 11 infertile men were incubated in vitro with [3H]progesterone before and during long term gonadotrophic treatment. The main metabolites along the delta-4 metabolic pathway and 20 alpha-dihydro-progesterone were determined and the ratio between 20 alpha-dihydro-progesterone and 17 alpha-hydroxyprogesterone formed in vitro was calculated. In 5 patients with originally high ratios (indicating gonadotrophic understimulation), steroid metabolism changed significantly towards a more stimulated pattern. Three of these patients also showed a significant increase in sperm output and 2 of them fathered children. In 6 patients with an originally low ratio (indicating adequate gonadotrophic stimulation) no change in steroid metabolism in vitro or spermatogenesis was seen during therapy. Thus, this ratio between formed 20 alpha-dihydro-progesterone and 17 alpha-hydroxyprogesterone in vitro seems to be of value in predicting whether gonadotrophic treatment will be of clinical benefit.
Adult↗
A new method for the determination of estrogen-2-hydroxylase activity.
A new method is described for determining the activity of a monooxygenase, acting by specific hydroxylation at the 2- position of the aromatic ring of estrogenic compounds with the formation of catechol estrogens. The procedure is based on separation of the catechol estrogen product from the substrate by high performance reversed-phase chromatography with amperometric detection in a thin-layer flow-cell by electrooxidation at a graphite-paste anode. Due to the very high detector sensitivity for the enzymatically generated product and an uncomplicated overall performance, the method offers great advantages over the radioenzymatic assay described earlier.
Animals↗
Calcium treatment of leg cramps in pregnancy. Effect on clinical symptoms and total serum and ionized serum calcium concentrations.
Up to 30 per cent of pregnant women suffer from leg cramps. The cause of these cramps is not known, but changes in calcium concentration have been suggested. Therefore 42 pregnant women with leg cramps were studied. No differences in total serum or ionized serum calcium concentrations were found as compared with a control group of pregnant women without leg cramps. Twenty-one patients were treated with 1 g calcium orally twice daily for 2 weeks and in this group good clinical improvement was achieved (p less than 0.001). The treatment increased the total serum calcium concentration from 2.25 mmol/l to 2.30 mmol/l but did not alter the ionized serum calcium concentration. Twenty-one untreated patients had the same frequency of cramps and showed no change in serum calcium concentrations throughout the investigation.
Adult↗
Effects of postmenopausal ethinylestradiol treatment on gallbladder bile.
Bile composition was studied in three postmenopausal women without evidence of gallstone disease during administration of 50 micrograms of ethinylestradiol daily. The treatment resulted in an increased fraction of cholesterol in gallbladder bile and a shift in the bile acid composition with decreased relative concentration of chenodeoxycholate and increased fraction of cholate. These changes in bile lipid composition might explain the higher incidence of gallstones in women treated with estrogens.
Bile Acids and Salts↗
Massive enlargement of occluded tubes after postmenopausal treatment with natural estrogens.
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Adnexal Diseases↗
On the in vitro metabolism of androstenedione and progesterone in human testicular tissue from fetal age to senescence.
The conversion of [3H]-androstenedione to testosterone regulated by the enzyme 17 beta-ketosteroid reductase and the conversion of [3H]-progesterone to 17 alpha-hydroxyprogesterone and onwards along the delta 4 metabolic pathway was studied in vitro in human testicular tissue from 32 males (2 fetuses, 25 adult, infertile men and 5 elderly men with prostatic carcinoma). Additionally, two prepubertal boys were studied with respect to the conversion of [3H]-androstenedione to testosterone in vitro, whereas another seven boys were studied with reference to the conversion of [3H]-progesterone in vitro. It appeared, that in all cases, the conversion of androstenedione to testosterone was larger than the conversion of progesterone to 17 alpha-hydroxyprogesterone by way of the 17 alpha-hydroxylase and onwards along the delta 4 metabolic pathway. It is thus concluded that the 17 beta ketosteroid reductase is not a rate-limiting enzyme along the delta 4 metabolic pathway. No case of deficient 17 beta-ketosteroid reductase was found among the 25 infertile patients studied.
Adolescent↗
Impaired Leydig cell function in vitro in testicular tissue from human males with "Sertoli cell only" syndrome.
Testicular histopathology in patients with "Sertoli Cell Only" Syndrome is characterized by absence of germinal cells. Some of these patients have high levels of LH in their peripheral blood as well as subnormal serum testosterone levels. This indicates a possible correlation between the lack of germinal cells and an impairment of Leydig cell steroidogenic activity. It has previously been shown that in vitro conversion of tritiated steroid precursors within testicular tissue indicates the Leydig cell steroidogenic activity. In this study we have investigated whether or not testicular tubular cell disorder with lack of germinal cells is related to impairment of the intratesticular steroid metabolism in vitro. Ten patients with testicular histopathology characteristic of "Sertoli cell only" syndrome were investigated and their steroid metabolism patterns were compared with those of 22 control patients. Leydig cell dysfunction was found in the group of patients with SOS; 17 alpha-hydroxylation was significantly lower and the production of 20 alpha-dihydroprogesterone was significantly higher, as compared to the control patients. The Leydig cell impairment may be due to a disturbed influence from the damaged tubules.
Follicle Stimulating Hormone↗
Impaired in vitro testicular endocrine function in elderly men.
Measurements of testosterone concentrations in peripheral and spermatic venous blood have yielded conflicting results concerning testosterone production in elderly men. To further elucidate the testicular endocrine capacity during aging, peripheral serum hormone levels and the in vitro conversion of progesterone and pregnenolone in histopathologically normal testicular tissue have been investigated in 22 elderly men and 28 younger adult males. The conversion mediated by 3 beta-hydroxysteroid-dehydrogenase and 17 alpha-hydroxylase was significantly higher (p less than 0.05 and p less than 0.01 respectively) in testicular tissue from the younger adult men, than in testicular tissue from elderly men. Since serum LH levels were significantly higher (p less than 0.01) and serum testosterone levels were significantly lower (p less than 0.01) in the elderly men, these data indicate that there was a primary endocrine impairment at the testicular level in the elderly men.
3-Hydroxysteroid Dehydrogenases↗
Testosterone production in vitro in human testicular tissue.
The biosynthesis of testosterone within the testis has been shown to take place along different metabolic pathways in different species. In the testis from elderly men with prostatic carcinoma the delta 5-metabolic pathway has been shown to be preferred. Less is known about the preferred pathway in younger adults. In this study, testicular biopsy specimens from 33 adults (ranging from 27 to 35 years of age) were incubated with both tritiated pregnenolone and progesterone. The production of testosterone from these precursors was determined in vitro and was found to be significantly higher from pregnenolone than from progesterone. This indicates that pregnenolone was initially mainly converted along the delta 5-metabolic pathway to 17 alpha-hydroxypregnenolone and probably further to dehydroepiandrosterone before it was subsequently transformed to a delta 4-metabolite. Similar results were obtained in incubation studies performed with testicular tissue from eleven elderly men (ranging from 60 to 83 years of age). In conclusion, studies of the testosterone production in vitro suggest that the delta 5-metabolic pathway is preferred in the testis from younger as well as elderly men.
17-alpha-Hydroxypregnenolone↗