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1.
Maturitas ; 61(1-2): 67-77, 2008.
Article in English | MEDLINE | ID: mdl-19434880

ABSTRACT

From a longitudinal prospective study, 160 women with spontaneous menopause and without steroid medication were followed during the transition from pre- to postmenopause. After 12 years 152 women were still participating in the study. Blood samples were drawn every 6 months until 1 year after the menopause and every 12 months thereafter. Measurements of bone mineral density (BMD) on the forearm were performed every second year. All women routinely completed a questionnaire concerning symptoms frequently attributed to the climacteric period. All data were grouped around the onset of the menopause, thereby allowing longitudinal evaluation of the changes in the variables from the premenopausal to the postmenopausal period. The beginning of the perimenopausal period was characterized by transitory elevations of follicle-stimulating hormone (FSH). A significant increase in serum levels of gonadotropins was observed for both FSH and luteinizing hormone (LH) from about 5 years before the menopause. Within the 6 month period around the menopause there was a further increase which culminated within the first postmenopausal year for LH and 2-3 years postmenopause for FSH. Thereafter, a continuous decrease in LH occurred over the following 8 years. With respect to FSH, there was a slight decline starting about 4 years postmenopause. During the premenopausal period an increasing frequency of inadequate luteal function or anovulation occurred and, in the postmenopausal years, the serum levels of progesterone (P) were invariably low. Gradually, the ratio between estrone (E1) and 17-beta-estradiol (E2) increased, reflecting the declining follicular steroidogenesis. A marked decrease in estrogen levels occurred during the 6 month period around the menopause, most pronounced in E2. During the next 3 years, the levels of E2 and E1 showed an essentially parallel, moderate decline. Around the menopause, serum levels of testosterone (T), delta4-androstenedione (A) and sex hormone-binding globulin (SHBG) showed small but significant decreases. From about 3 years postmenopause, the levels were relatively constant over the following 5 years. A decrease in BMD was observed in the postmenopause, and from about 3 years postmenopause, estradiol correlated positively with BMD. Before, as well as after the menopause, body mass index (BMI) showed an inverse correlation with SHBG. Postmenopausal androstenedione correlated positively with E1, E2 and T. BMI correlated positively with E1 and E2. The concentrations of the free fraction of E2 and T are dependent on the levels of SHBG, which in turn has a negative correlation with BMI. The impact of this will influence the severity of symptoms, the degree of bone loss and the need for supplementary therapy.

2.
Mol Ecol ; 14(13): 3951-63, 2005 Nov.
Article in English | MEDLINE | ID: mdl-16262851

ABSTRACT

Population contribution to genetic diversity can be estimated using neutral variation. However, population expansion or hybridization of diverged ancestries may weaken correlation between neutral and non-neutral variation. Microsatellite variation was studied at 25 loci in 20 native and 12 modern or imported northern European sheep breeds. Breed contributions to total gene diversity, allelic richness and mean allele-sharing distance between individuals were measured. Indications of changes in population size and admixtures of divergent ancestries were investigated and the extent of inbreeding was estimated. The northern European sheep demonstrated signs of reduction in effective population size. Many old, small populations made a substantial positive contribution to total molecular variation, but populations with several divergent major ancestries did not contribute substantially to molecular variation, with the exception of the Norwegian Rygja sheep. However, several diverged major ancestries may cause it to contribute less to non-neutral variation than expected from the microsatellite data. Breed uniqueness and within-breed variability generally had opposite effects on breed contributions to molecular diversity. The degree of inbreeding did not reflect the breed contribution to total gene diversity or allelic richness, but inbred populations increased the mean allele-sharing distance between individuals. Our study indicates breed conservation to be especially important in maintaining allelic variation in northern European sheep and supports the evolutionary importance of peripheral populations.


Subject(s)
Genetic Variation , Genetics, Population , Inbreeding , Sheep/genetics , Animals , Conservation of Natural Resources , Europe , Gene Frequency , Microsatellite Repeats/genetics , Population Density , Species Specificity
3.
Heredity (Edinb) ; 94(4): 448-56, 2005 Apr.
Article in English | MEDLINE | ID: mdl-15674382

ABSTRACT

Studies of domestic animals are performed on breeds, but a breed does not necessarily equate to a genetically defined population. The division of sheep from three native and four modern Baltic sheep breeds was studied using 21 microsatellite loci and applying a Bayesian clustering method. A traditional breed-wise approach was compared to that relying on the pattern of molecular diversity. In this study, a breed was found to be inconsistent with a distinct genetic population for three reasons: (i) a lack of differentiation between modern Baltic breeds, since the majority of the studied sheep formed a single population; (ii) the presence of individuals of foreign ancestry within the breed; and (iii) an undefined local Saaremaa sheep was referred to as a breed, but was shown to consist of separate populations. In the breed-wise approach, only the clearly distinct Ruhnu sheep demonstrated low within-breed variation, although the newly identified Saaremaa populations also have low variability. Providing adequate management recommendations for the Saaremaa sheep is not possible without further studies, but the potential harmful effects of inbreeding in the Ruhnu sheep could be reduced through the use of two genetically related Saaremaa populations. In other breeds, excessive crossing appears to be a larger concern than inbreeding. Assigning individuals into populations based on the pattern of genetic diversity offers potentially unbiased means of elucidating the genetic population structure of species. Combining these genetic populations with phenotypic and aetiological data will enable formulation of the most informed recommendations for gene resource management.


Subject(s)
Genetic Variation/genetics , Inbreeding , Linkage Disequilibrium/genetics , Microsatellite Repeats/genetics , Sheep, Domestic/genetics , Animals , Baltic States , Crosses, Genetic , Genetic Markers , Genetics, Population , Quantitative Trait, Heritable , Species Specificity
4.
Horm Metab Res ; 34(10): 583-8, 2002 Oct.
Article in English | MEDLINE | ID: mdl-12439787

ABSTRACT

The effects of estrogen replacement therapy on lipid and glucose metabolism as related to abdominal fat distribution were investigated in fifty-one healthy postmenopausal women aged 52-53 years. They were randomized to treatment with either estradiol 2 mg or placebo daily for three months in a double-blind design. Forty-six women continued with estradiol for another nine months in an open design with the addition of medroxyprogesterone for ten days every three months. Intra-abdominal and subcutaneous abdominal fat, and intrapelvic and subcutaneous pelvic fat was estimated by computed tomography before and after one year of estrogen treatment. Euglycemic hyperinsulinemic clamp, oral glucose tolerance test and analyses of blood lipids were performed after 3 and 12 months of treatment. Estrogen replacement therapy decreased body fat mass as well as intra-abdominal and intrapelvic fat, but not the subcutaneous fat compartments. LDL cholesterol decreased and HDL cholesterol increased, whereas triglycerides were not changed by one year of estrogen treatment. Insulin sensitivity and glucose tolerance were not affected by estrogen treatment. In postmenopausal women estrogen treatment for one year decreased intra-abdominal and intrapelvic fat compartments, but this was not related to changes in plasma lipid levels. Insulin sensitivity and plasma triglycerides were not affected by estrogen treatment.


Subject(s)
Adipose Tissue/metabolism , Estrogen Replacement Therapy , Glucose/metabolism , Lipid Metabolism , Abdomen/anatomy & histology , Apolipoproteins/blood , Body Composition , Cholesterol/blood , Double-Blind Method , Exercise Test , Fatty Acids, Nonesterified/blood , Female , Glucose Tolerance Test , Humans , Hydrocortisone/blood , Insulin/metabolism , Insulin-Like Growth Factor I/metabolism , Leptin/blood , Middle Aged , Postmenopause/metabolism , Tomography, X-Ray Computed , Triglycerides/blood
5.
Bone ; 28(3): 327-31, 2001 Mar.
Article in English | MEDLINE | ID: mdl-11248665

ABSTRACT

This prospective study evaluated bone loss in the peri- and postmenopausal period in 156 women followed from age 48 to 64 years. All women were premenopausal at the start of the study. Areal bone mineral density (g/cm(2)) was measured by single-photon absorptiometry (SPA) of the forearm at the 1 cm level (BMD 1 cm) and the 6 cm level (BMD 6 cm) every second year. Onset of menopause (MP) was determined according to the criteria of the World Health Organization (12 months of amenorrhea and elevated follicle-stimulating hormone). At the end of the study, 125 of 156 women (80%) remained. Bone mineral density (BMD) at age 48 years correlated with BMD at age 64 years within the respective region (r = 0.4-0.5, p < 0.001, respectively). There was no BMD loss in the premenopausal period. BMD loss was accelerated at menopause (MP) independent of chronological age. BMD loss was greater during the first 5 years following MP than during the following 6 years (BMD 1 cm 2.4% per year [1.0%-3.9%] vs. 0.4% per year [-0.3%-1.0%], p < 0.01). The quartile of women with late MP (>53.7 years) had greater bone loss during the first 5 years after MP than the quartile of women with early MP (<50.3 years) (p < 0.001). At age 64 years, BMD was no different when comparing the quartile of women with late MP vs. the quartile of women with early MP. Furthermore, there was no correlation between age at menopause and BMD at the age of 64. In summary, among women still menstruating at age 48 years, there was no measurable BMD loss in the premenopausal period. Independent of chronological age, BMD loss accelerated during MP. Rates of loss were highest in the early postmenopausal period. Independent of age at MP, premenopausal women with low age-specific BMD at age 48 years had an increased risk of sustaining low BMD at age 64 years also.


Subject(s)
Menopause , Osteoporosis/physiopathology , Female , Humans , Middle Aged , Prospective Studies
6.
Maturitas ; 21(2): 103-13, 1995 Feb.
Article in English | MEDLINE | ID: mdl-7752947

ABSTRACT

From a longitudinal prospective study, 160 women with spontaneous menopause and without steroid medication were followed during the transition from pre- to postmenopause. After 12 years 152 women were still participating in the study. Blood samples were drawn every 6 months until 1 year after the menopause and every 12 months thereafter. Measurements of bone mineral density (BMD) on the forearm were performed every second year. All women routinely completed a questionnaire concerning symptoms frequently attributed to the climacteric period. All data were grouped around the onset of the menopause, thereby allowing longitudinal evaluation of the changes in the variables from the premenopausal to the postmenopausal period. The beginning of the perimenopausal period was characterized by transitory elevations of follicle-stimulating hormone (FSH). A significant increase in serum levels of gonadotropins was observed for both FSH and luteinizing hormone (LH) from about 5 years before the menopause. Within the 6 month period around the menopause there was a further increase which culminated within the first postmenopausal year for LH and 2-3 years postmenopause for FSH. Thereafter, a continuous decrease in LH occurred over the following 8 years. With respect to FSH, there was a slight decline starting about 4 years postmenopause. During the premenopausal period an increasing frequency of inadequate luteal function or anovulation occurred and, in the postmenopausal years, the serum levels of progesterone (P) were invariably low. Gradually, the ratio between estrone (E1) and 17-beta-estradiol (E2) increased, reflecting the declining follicular steroidogenesis. A marked decrease in estrogen levels occurred during the 6 month period around the menopause, most pronounced in E2. During the next 3 years, the levels of E2 and E1 showed an essentially parallel, moderate decline. Around the menopause, serum levels of testosterone (T), delta 4-androstenedione (A) and sex hormone-binding globulin (SHBG) showed small but significant decreases. From about 3 years postmenopause, the levels were relatively constant over the following 5 years. A decrease in BMD was observed in the postmenopause, and from about 3 years postmenopause, estradiol correlated positively with BMD. Before, as well as after the menopause, body mass index (BMI) showed an inverse correlation with SHBG. Postmenopausal androstenedione correlated positively with E1, E2 and T. BMI correlated positively with E1 and E2. The concentrations of the free fraction of E2 and T are dependent on the levels of SHBG, which in turn has a negative correlation with BMI. The impact of this will influence the severity of symptoms, the degree of bone loss and the need for supplementary therapy.


Subject(s)
Bone Density , Climacteric/metabolism , Gonadal Steroid Hormones/blood , Gonadotropins, Pituitary/blood , Sex Hormone-Binding Globulin/analysis , Androstenedione/blood , Body Mass Index , Estradiol/blood , Estrone/blood , Female , Follicle Stimulating Hormone/blood , Humans , Longitudinal Studies , Luteinizing Hormone/blood , Menopause/metabolism , Middle Aged , Postmenopause/metabolism , Premenopause/metabolism , Prospective Studies , Testosterone/blood
7.
Fertil Steril ; 51(4): 616-21, 1989 Apr.
Article in English | MEDLINE | ID: mdl-2924930

ABSTRACT

Blood samples collected longitudinally in 17 women over a period of 3 years, starting 11/2 years before the menopause, were assessed for sex hormone-binding globulin (SHBG), 17 beta-estradiol (E2), progesterone, and total testosterone. A slight (7.2%) decrease in mean SHBG from 4.25 +/- 1.67 (standard deviation) mg/l to 3.95 +/- 1.61 mg/l was observed within the 6-month period encompassing the menopause. More specifically, the decrease appeared to commence at the menopause and to become clearly significant (P = 0.01) some 2 to 6 months later. During the subsequent year, a further decrease to 3.64 +/- 1.42 mg/l was observed, amounting to a total decrease in mean SHBG by 14.4% (P less than 0.001). Of the hormones, only E2 exhibited a marked decrease (P less than 0.01) within this same 6-month period. The changes in SHBG during the 6-month transition period from premenopause to postmenopause correlated significantly (P = 0.013) only with those of E2. It is concluded that decreasing E2 levels appear to play a significant role in the downward modulation of SHBG levels commencing at the menopause.


Subject(s)
Gonadal Steroid Hormones/blood , Menopause/blood , Sex Hormone-Binding Globulin/analysis , Estradiol/blood , Female , Humans , Longitudinal Studies , Middle Aged , Testosterone/blood
8.
Maturitas ; 8(4): 297-307, 1986 Dec.
Article in English | MEDLINE | ID: mdl-2952867

ABSTRACT

To permit a more detailed hormonal characterization of the peri-menopause, 30 healthy women were examined at regular intervals over a 7-yr period, starting about 3 yr before the menopause. Even though most of the subjects periodically experienced climacteric symptoms, no hormonal supplementation was given. The serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), oestradiol and oestrone that were recorded essentially confirmed previous data obtained in cross-sectional studies. Within the 6-mth period around the menopause the serum levels of testosterone and androstenedione showed small but significant decreases of 18 and 16%, respectively. These decreases continued over the following years and amounted to about 30% after 3 yr. In contrast, neither the mean level of dehydroepiandrosterone (DHA) nor the DHA/DHA sulphate (DHAS) ratio changed significantly at the menopause, but DHA and DHAS concentrations declined slowly by about 20% over the 7-yr observation period. The mean level of DHAS showed an isolated increase during the last few months before the menopause. A similar, although not significant, increase was also seen in DHA and testosterone levels. After the first post-menopausal year a significant positive correlation was found between the levels of oestrone and androstenedione. This longitudinal study of individual women appeared to lend itself well to the investigation of even subtle hormonal fluctuations during the gradual transition to an established post-menopausal pattern.


Subject(s)
Androstenedione/blood , Dehydroepiandrosterone/analogs & derivatives , Dehydroepiandrosterone/blood , Estradiol/blood , Estrone/blood , Menopause , Testosterone/blood , Dehydroepiandrosterone Sulfate , Female , Humans , Middle Aged , Prospective Studies , Time Factors
9.
Acta Obstet Gynecol Scand ; 65(3): 207-10, 1986.
Article in English | MEDLINE | ID: mdl-3090850

ABSTRACT

The concentrations of FSH, LH, 17-beta-estradiol (E2), estrone (E1) and progesterone (P) were measured in peripheral and ovarian vein sera obtained at preoperative pelvic angiography from 5 postmenopausal women with malignant ovarian tumors. In 5 others the concentrations of E2, P and testosterone (T) were also measured in ascitic fluid collected at laparotomy. The investigation showed that most of these patients had increased concentrations of E2 and/or E1 and P as well in the peripheral blood. Significant gradients between the ovarian and peripheral vein concentrations were found for E2 and for P. High levels of E2, P and T were found in the ascitic fluid. FSH and LH levels were often lowered in peripheral blood compared with normal menopausal values and a gradient to ovarian tumor venous blood - with lower concentrations in the blood coming from the tumors, was found. Endometrial histology showed signs of steroid stimulation. These cases indicate that malignant ovarian tumors and/or the ovaries harboring them, are often capable of producing different sex steroids. These steroids may be found in the peripheral blood and in the ascitic fluid compartment and therefore may be used as tumor markers. The steroid production is probably not autonomous, but gonadotropin-dependent.


Subject(s)
Endometrium/pathology , Gonadal Steroid Hormones/blood , Gonadotropins, Pituitary/blood , Menopause , Ovarian Neoplasms/blood , Adult , Estradiol/blood , Estrone/blood , Female , Follicle Stimulating Hormone/blood , Humans , Luteinizing Hormone/blood , Middle Aged , Ovarian Neoplasms/pathology , Progesterone/blood , Testosterone/blood
10.
Am J Pathol ; 121(2): 337-41, 1985 Nov.
Article in English | MEDLINE | ID: mdl-4061568

ABSTRACT

In a study of the morphologic effects of various steroid hormones on human uterine endometrium and endometriotic tissue, specimens from 6 women were transplanted subcutaneously into 24 nude mice. In each case, specimens collected simultaneously were transplanted to 4 mice, endometrium to one lateral abdominal wall and endometriotic tissue to the other. All mice were given polyestradiol phosphate subcutaneously the first day after operation. After a 2-week interval, of each 4 mice, 1 mouse was given polyestradiol phosphate, 1 medroxyprogesterone acetate, 1 danazol, and 1 no further injections. This treatment continued for 8 weeks, after which the mice were killed and the grafts extirpated. Histologic changes in the grafts varied according to the treatment schedule but were very similar in both types of tissue. Our findings suggest that histologic differences between endometrium and endometriotic tissue seen under natural conditions may, at least partly, be due to variations in environmental factors.


Subject(s)
Endometriosis/pathology , Endometrium/pathology , Hormones/pharmacology , Uterus/anatomy & histology , Adult , Animals , Danazol/pharmacology , Estradiol/analogs & derivatives , Estradiol/pharmacology , Female , Humans , Medroxyprogesterone/pharmacology , Mice , Mice, Nude , Transplantation, Heterologous , Uterus/transplantation
11.
Am J Pathol ; 119(2): 336-44, 1985 May.
Article in English | MEDLINE | ID: mdl-3158210

ABSTRACT

In a histologic study of human endometrium transplanted into nude mice, eutopic endometrium from each of 8 women was transplanted subcutaneously to 4 nude mice, 1 of which was treated with polyestradiol phosphate, 1 with MPA, 1 with danazol, and 1 of which was left untreated as a control. Grafts were removed after varying intervals of up to 57 days. Residual histologically evaluable endometrial tissue was found in 32 of the 96 grafts (33%). None of the extirpated grafts had the same histologic pattern as the eutopic endometrium. Besides confirming that human endometrium can be transplanted into nude mice, our findings suggest that grafts react histologically in the same way as eutopic human endometrium to hormone treatment. The specific stroma seems to be crucial to a graft's capacity to respond to hormonal stimuli, and its replacement by fibrous tissue was accompanied by glandular epithelial changes very similar to those seen in human endometriotic lesions.


Subject(s)
Danazol/pharmacology , Endometrium/transplantation , Estradiol/analogs & derivatives , Medroxyprogesterone/analogs & derivatives , Pregnadienes/pharmacology , Transplantation, Heterologous , Adult , Animals , Endometrium/anatomy & histology , Endometrium/drug effects , Estradiol/pharmacology , Female , Humans , Medroxyprogesterone/pharmacology , Medroxyprogesterone Acetate , Mice , Mice, Nude , Middle Aged
12.
J Histochem Cytochem ; 33(2): 155-61, 1985 Feb.
Article in English | MEDLINE | ID: mdl-3968421

ABSTRACT

Estrogen and progesterone binding to endometriotic and endometrial tissue was studied histochemically using estradiol and progesterone fluorochrome derivatives (E2-bovine serum albumin-fluorescein isothiocyanate and progesterone-bovine serum albumin-tetramethylrhodamine isothiocyanate). Thirty endometriotic samples from 21 women were studied, together with endometrial specimens obtained simultaneously from 14 of the women. In 77% of the endometriotic samples binding of the estrogen conjugate was indicated by specific fluorescence in more than half of the epithelial cell population, and in 20% in less than half. The corresponding figures for the progesterone conjugate binding were 75 and 18%, respectively. Blocking studies indicated a reasonable degree of ligand specificity. In endometrial tissue the corresponding figures were 64 and 29%, respectively, for binding of the estrogen conjugate and 54 and 38%, respectively, for binding of the progesterone conjugate. In 7 of 13 cases where evaluable samples of both tissues had been obtained, the relative proportion of fluorescent cells, with either reagent, was similar in the two tissue types. Our results suggest that the cytoplasm of epithelial cells in endometriotic tissue and in uterine endometrium contains specific binding sites for both estrogen and progesterone. The binding pattern of the two conjugates in endometriotic tissue was unrelated to the menstrual phase.


Subject(s)
Endometriosis/metabolism , Endometrium/metabolism , Estrogens/metabolism , Progesterone/metabolism , Adolescent , Adult , Epithelium/metabolism , Female , Fluorescence , Histocytochemistry , Humans , Menstrual Cycle
13.
Article in English | MEDLINE | ID: mdl-6238497

ABSTRACT

One hundred and sixteen patients with laparoscopically confirmed primary or recurrent endometriosis were treated with danazol, either 600 mg daily for 4 months (group A, n = 76) or 600 mg daily for the first 2 months, followed by 400 mg daily for an additional 4 months (group B, n = 40). The only surgery performed before treatment was biopsies, resection of endometriomas greater than or equal to 3 cm and/or adhesiolysis. The extent of endometriosis before and after treatment was established laparoscopically and recorded by means of a modified AFSrecord as mean additive diameter of implants (mean ADI) in millimeters. This provided a uniform and reproducible quantitative registration for each type and location of endometriotic implant. Both treatment schemes resulted in a highly significant (p less than 0.001) reduction of endometriosis, by 79 and 89% in groups A and B, respectively. However, the reduction in mean ADI was significantly greater (p less than 0.025) in group B which had been treated for a longer period. Moreover, the proportion of patients with extensive pre-treatment lesions (mean ADI greater than or equal to 40 mm) was significantly greater in this group. Active residual endometriosis was found in 21 and 17.5% in groups A and B, respectively. These patients had significantly more extensive endometriosis before treatment. The regression of endometriotic implants was independent of type and/or location, i.e. superficial or scarred; peritoneal, ovarian, or tubal. There was no apparent correlation between the quantitative reduction of endometriosis and amenorrhea versus occasional spotting and/or irregular menstruations.(ABSTRACT TRUNCATED AT 250 WORDS)


Subject(s)
Danazol/administration & dosage , Endometriosis/drug therapy , Pregnadienes/administration & dosage , Adult , Amenorrhea/complications , Endometriosis/complications , Endometriosis/diagnosis , Female , Humans , Laparoscopy , Scandinavian and Nordic Countries
14.
Article in English | MEDLINE | ID: mdl-6594006

ABSTRACT

A histochemical method for the detection of steroid-binding sites in very small tissue specimens was evaluated. Competitive binding experiments proved the method to be sufficiently specific. When applied to endometrium and endometriotic tissue obtained simultaneously from the same patient, a distinct binding was found both in the epithelial structures and in the stroma. The binding pattern in endometriotic glands resembled that in the endometrium. The study seems thus to support the conclusion that endometriotic lesions contain specific binding sites for estrogen and progesterone and that their distribution seems to be similar to that found in the endometrium from the same patient.


Subject(s)
Endometriosis/metabolism , Endometrium/metabolism , Estrogens/metabolism , Progesterone/metabolism , Adult , Binding, Competitive , Female , Histocytochemistry , Humans , Middle Aged
15.
Article in English | MEDLINE | ID: mdl-6594016

ABSTRACT

The synthetic steroid danazol has rapidly become the drug most commonly used in the hormonal treatment of endometriosis and its clinical and endocrine properties in women have been investigated extensively. However, little is known about the early effects of danazol on the endometrium. This study was performed in order to discover how soon after institution of danazol therapy atrophic changes can be observed in the endometrium. Ten patients with fibromyoma of the uterus and menorrhagia were treated with danazol at a dosage of 600 mg a day. During treatment, plasma estradiol values corresponded to those of the early follicular phase of a normal menstrual cycle. In 5 of the patients, endometrial biopsies were obtained after 8 weeks of therapy. Four of them had a thin endometrium of atrophic histological appearance. In view of these findings, biopsies were taken from a further 5 patients after only 4 weeks' treatment. All of these biopsies revealed a reduced endometrium and 3 of the 5 endometria were histologically clearly atrophic. Even if total resorption of endometriotic tissue usually takes a considerable time, the finding of atrophy of the uterine endometrium induced by danazol after only 4 weeks of treatment is consistent with the rapid improvement in clinical symptoms in patients with endometriosis.


Subject(s)
Danazol/therapeutic use , Endometriosis/drug therapy , Pregnadienes/therapeutic use , Adult , Endometriosis/pathology , Female , Humans , Middle Aged
16.
Article in English | MEDLINE | ID: mdl-6437126

ABSTRACT

During treatment with danazol the serum concentration of thyroxin-binding globulin (TBG) decreases. This effect is probably a direct effect on TBG production at the cellular level. In order to exclude an indirect effect on TBG production via the well known suppressing effect of danazol on serum estrogen concentrations, the following study was performed. Twelve healthy female volunteers, who were at least 3 years past the menopause and with serum-estradiol levels below 100 pmol/l, were treated with danazol in dosages of 400, 600 or 800 mg daily. The concentrations of TBG, TSH, total thyroxin (T4), total triiodothyronine (T3) and free dialysable fractions of T4 and T3 were determined, before, and after 2 and 4 weeks of medications. The serum concentrations of TBG, total T4 and T3 decreased. The TSH concentration and the free dialysable fraction of T4 were essentially unaltered after 2 weeks but the TSH had decreased slightly and free T4 increased slightly after 4 weeks. The free dialysable fraction of T3 decreased transiently at 2 weeks. All the observations proved to be independent of the three dosages of danazol applied in this study. In conclusion, danazol treatment influences available tests of thyroid function by reducing the concentration of TBG. This is most probably a direct effect of the drug, and it is clearly independent of the effect on estrogen production. Clinically there is no evidence of a decreased effect of thyroid hormones on the target organs.


Subject(s)
Danazol/pharmacology , Pregnadienes/pharmacology , Thyroid Hormones/blood , Aged , Female , Humans , Middle Aged , Thyrotropin/blood , Thyroxine/blood , Thyroxine-Binding Proteins/blood , Triiodothyronine/blood
17.
Article in English | MEDLINE | ID: mdl-6437128

ABSTRACT

The antigonadotropic action of danazol is still a subject of controversy. Danazol does not cause a consistent and significant suppression of basal gonadotropin concentrations in premenopausal women. In order to investigate the possible effects of danazol on circulating gonadotropin levels in the absence of gonadal feedback, postmenopausal women were studied. Twelve healthy women, at least 3 years past the menopause, volunteered. Their mean age was 61.1 +/- 5.5 (SD) years. Danazol in daily doses of 400, 600 or 800 mg was given randomized, to 4 patients each, for 4 weeks. Venous samples were drawn at -1, 0, +1, +2, +4 weeks of medication. FSH and LH in serum were measured by means of double antibody radio-immunoassay. There was no significant difference between any of the pre-treatment means in the three dose groups. After 4 weeks of danazol treatment, FSH had decreased by 18%, 31%, and 32% in the 400, 600 and 800 mg groups, respectively. The corresponding decreases in LH were 14%, 24% and 21%. There was no significant dose response between any of the doses used. In the absence of significant differences between the pre-treatment means and of significant dose response, data for all 12 patients were pooled for statistical evaluation. The mean decrease in FSH was significant only after 4 weeks (-4.8 micrograms/l; p less than 0.001). The mean decrease in LH was significant after 1, 2 and 4 weeks of treatment (-1.0 to -1.13; p less than 0.01 or less).(ABSTRACT TRUNCATED AT 250 WORDS)


Subject(s)
Danazol/pharmacology , Gonadotropins, Pituitary/blood , Pregnadienes/pharmacology , Aged , Female , Follicle Stimulating Hormone/blood , Humans , Luteinizing Hormone/blood , Menopause , Middle Aged
18.
Acta Endocrinol (Copenh) ; 99(3): 339-43, 1982 Mar.
Article in English | MEDLINE | ID: mdl-6461995

ABSTRACT

The aim of the study was to evaluate the functional state of the hypothalamo-pituitary-gonadal axis and to assess the concentrations of MPA in the peripheral blood during very long-term use of depo-medroxyprogesterone acetate (DMPA) as a contraceptive agent. The concentrations of MPA, sex-hormone binding globulin (SHBG) and the different pituitary and gonadal hormones in the peripheral blood were measured in nine 26-41 year old women. They had for 4.4-10.6 years (mean 8.9 years) been receiving DMPA im in a dose of 150 mg every 12th week as a contraceptive. Blood samples were obtained immediately before an injection of DMPA, 2 weeks later, and again immediately before the next injection. SHBG was measured by radio-electro-immunoassay; MPA, gonadal and pituitary hormones by RIA. The investigation showed that the oestradiol levels - even after very long-term use of DMPA - were still within the normal range for the early follicular phase. Gonadotrophins and prolactin were within the normal range for eumenorrhoeic women as well as the concentration of SHBG. MPA did not accumulate in the plasma. The changes in the plasma levels of oestradiol, MPA and SHBG after each injection disappeared within 12 weeks. The study appearts to warrant the conclusion that even up to 10 years' use of DMPA in a dose of 150 mg im every 12th week as a contraceptive agent, does not induce hormonal changes different from those seen after the very first injection.


Subject(s)
Contraceptives, Oral, Hormonal/pharmacology , Contraceptives, Oral/pharmacology , Gonadal Steroid Hormones/blood , Gonadotropins, Pituitary/blood , Medroxyprogesterone/analogs & derivatives , Sex Hormone-Binding Globulin/blood , Adult , Amenorrhea/chemically induced , Delayed-Action Preparations/pharmacology , Female , Humans , Medroxyprogesterone/adverse effects , Medroxyprogesterone/blood , Medroxyprogesterone/pharmacology , Medroxyprogesterone Acetate , Middle Aged , Progesterone/blood , Prolactin/blood , Time Factors
20.
Acta Paediatr Scand ; 70(4): 595-7, 1981 Jul.
Article in English | MEDLINE | ID: mdl-7315307

ABSTRACT

Recurrent abdominal pains occur in about 11% of children. Of these about 8% have an organic etiology. That a spinal cord tumor, especially the intramedullary type, may present with abdominal pains as the initial symptom is unknown in paediatric circles. To highlight this problem two patients are reported. Early diagnosis is essential. The most important clues to a spinal cord tumor are pain, progressive paralysis, and a sensory level. In children with recurrent abdominal pains of unclear etiology the possibility of a spinal cord tumor must be kept in mind and lead to appropriate investigations.


Subject(s)
Abdomen , Astrocytoma/complications , Ependymoma/complications , Pain/etiology , Spinal Cord Neoplasms/complications , Astrocytoma/diagnosis , Child , Child, Preschool , Ependymoma/diagnosis , Humans , Male , Recurrence , Spinal Cord Neoplasms/diagnosis
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