Biomedical subjects

Inga-Stina Odmark

Publications and source records attributed to Inga-Stina Odmark.

5 recordsLinked to original sources

PubMed2005

Endometrial safety and bleeding pattern during a five-year treatment with long-cycle hormone therapy.

OBJECTIVE: To determine compliance, the incidence of untoward effects, and endometrial safety in postmenopausal women treated with 3-month sequential hormone therapy for up to 5 years. DESIGN: A prospective, uncontrolled multicenter study of 129 women treated with 0.625 mg conjugated estrogens daily plus 10 mg medroxyprogesterone acetate for 14 days every third month. Endometrial biopsy samples were taken before the initiation of the study and then yearly during the next 5 years. Bleeding patterns were recorded. RESULTS: Upon completion of the first 12 months of treatment, 76 of 126 biopsied women (60%) had secretory endometrium. After 5 years, this finding was reversed in biopsy specimens completed by 59 women, among whom 32 (56%) had insufficient or atrophic endometrium. We did not find any hyperplasia when the biopsy specimen was taken according to the protocol. One endometrial cancer was found by biopsy after 12 months, but the subsequent hysterectomy showed no sign of cancer. Ultrasound determinations of mean endometrial thickness during therapy showed a thin endometrium (mean = 4 mm, range = 1-13 mm). Amenorrhea was reported by 6.2% of 129 women after 12 months of treatment. Among the 59 women who completed the study, 71.2% had regular bleeding patterns every third month, 25.4% reported amenorrhea, and 3.4% had irregular bleeding patterns. CONCLUSIONS: The addition of 10 mg of medroxyprogesterone acetate for 14 days every third month to treatment with 0.625 mg of conjugated estrogens daily was well tolerated, and was associated with high endometrial safety.

Biopsy↗

PubMed2005

Conjugated estrogen/progestagen versus tibolone hormone replacement therapy in postmenopausal women: Effects on carbohydrate metabolism and serum sex hormone-binding globulin.

OBJECTIVE: To study the effects of different types of continuous hormone replacement therapy on carbohydrate metabolism. METHOD: Postmenopausal women were treated with conjugated estrogens, 0.625 mg/medroxyprogesterone acetate, 2.5 or 5 mg (CEE/MPA) or tibolone 2.5 mg daily for 13 28-day cycles. Serum glucose and insulin were measured before and during a 75 g oral glucose tolerance test (OGTT) at baseline and after 3, 6 and 13 cycles and areas under the curve (AUC) were calculated. Sex hormone-binding globulin (SHBG) was measured as an additional marker of nutritional and insulin status. RESULTS: Neither CEE/MPA 2.5mg nor tibolone had any effects on carbohydrate metabolism while AUC(insulin), AUC(glucose) and also body mass index (BMI) increased after 13 cycles of treatment in the CEE/MPA 5 mg group. SHBG increased significantly during CEE/MPA treatment and decreased significantly during treatment with tibolone. The effects on SHBG were less pronounced in the CEE/MPA 5mg group. Pretreatment SHBG showed significant negative correlations to BMI and to variables that may reflect a certain degree of insulin resistance, the most pronounced being fasting glucose. Changes in SHBG during treatment with tibolone were negatively correlated to pretreatment SHBG and positively to BMI, AUC(insulin) and fasting insulin resistance index, while no such correlations were found in the CEE/MPA groups. There were no correlations between changes in AUC(insulin) and AUC(glucose) on one hand and basal variables or treatment SHBG on the other in the CEE/MPA groups. CONCLUSION: The effects of tibolone and CEE/MPA on carbohydrate metabolism were considered to have clinical significance only for CEE/MPA 5mg, indicating a less favourable role of the higher progestagen dose. The results further support the important role of metabolic and insulin status in the physiological regulation of SHBG and also indicate that the suppressive effect of tibolone on circulating SHBG is mainly depends on pretreatment SHBG levels. SHBG does not reflect changes in carbohydrate metabolism during CEE/MPA treatment.

Aged↗

PubMed2004

Apoptosis, proliferation, and sex steroid receptors in postmenopausal endometrium before and during HRT.

OBJECTIVES: Endometrial homeostasis, indicated as the balance between apoptosis and proliferation, was studied with regard to endometrial safety and bleeding disturbances. MATERIALS AND METHODS: The quantitatively sufficient endometrial biopsies of 92 postmenopausal women enrolled in the study were investigated. The participants were divided into two groups, each receiving a continuous combined HRT regimen with either conjugated estrogen (CE) 0.625 mg + 5 mg medroxyprogesterone acetate (MPA) (=CE/MPA) or 17-beta-estradiol (E2) 2 mg + 1 mg norethisterone acetate (NETA) (=E2/NETA). These were evaluated according to apoptotic index (Ai) and proliferation marker Ki-67 index. Estrogen receptor alpha (ER) and progesterone receptor (PR) expression were also monitored, as well as endometrial thickness. Quantitative in situ techniques were used. RESULTS: Ai and Ki-67 index were unchanged in epithelial glands of endometrium from baseline to second biopsy obtained after 1 year of combined continuous HRT. In stromal tissue, Ki-67 index was increased, while Ai was on the same level. PR expression in both epithelium and stroma was unchanged. Endometrial thickness was unaffected during therapy, and the histopathological evaluation showed no development of hyperplasia or carcinoma. CONCLUSIONS: The unaffected homeostasis in endometrial epithelium contributes to endometrial safety and is in accordance with the histopathological findings of no hyperplasia. The homeostasis of stroma was transformed to be more proliferative. Increased stromal proliferation may be of importance for stromal support of the veins and for decreasing breakthrough bleeding during HRT. The increased stromal proliferation, as well as the decreased ER expression both in epithelium and stroma, could be an effect of progesterone.

Apoptosis↗

PubMed2004

Effects of continuous combined conjugated estrogen/medroxyprogesterone acetate and 17beta-estadiol/norethisterone acetate on lipids and lipoproteins.

OBJECTIVES: Various estrogen/progestogen combinations used in hormonal replacement therapy (HRT) have been reported to influence lipid and lipoprotein fractions differently. This motivated a comparative study where the two continuous combined regimens most commonly used in Sweden during the 1990s have been studied regarding effects on lipid profile. METHODS: In a 1-year prospective, double-blind study, 62 post-menopausal women were randomized to conjugated estrogen (CE), 0.625 mg, and medroxyprogesterone acetate (MPA), 5 mg, or 17beta-estradiol (E2), 2 mg, and norethisterone acetate (NETA), 1 mg. Serum concentrations of lipids and lipoproteins were measured at baseline and after 1 year of treatment. RESULTS: Both treatment groups significantly lowered the lipoprotein(a) (Lp(a)) levels. The CE/MPA group showed no significant changes in total cholesterol (TC), high-density (HDL) and low-density lipoprotein (LDL), but a significant increase of triglyceride (TG) levels. The E2/NETA group developed a significant lowering of total cholesterol, HDL, and LDL, but no significant changes of TG levels. The magnitude of change in serum concentrations of total cholesterol, HDL and TG differed significantly between the two treatment groups. CONCLUSIONS: Continuous combined treatment with CE/MPA and E2/NETA equally lowered Lp(a), an important risk factor for cardiovascular disease in women. Apart from this, the two treatments produced different effects on lipids and lipoproteins, findings that are more delicate to interpret.

Cholesterol↗

PubMed2003

Pathogenesis in menstrual cycle-linked CNS disorders.

That 3alpha-hydroxy-5alpha/beta-pregnane steroids (GABA steroids) have modulatory effects on the GABA-A receptor is well known. In behavioral studies in animals high exogenous dosages give concentrations not usually reached in the brain under physiological conditions. Animal and human studies show that GABA-A receptor-positive modulators like barbiturates, benzodiazepines, alcohol, and allopregnanolone have a bimodal effect. In pharmacological concentrations they are CNS depressants, anesthetic, antiepileptic, and anxiolytic. In low dosages and concentrations, reached endogenously, they can induce adverse emotional reactions in up to 20% of individuals. GABA steroids can also induce tolerance to themselves and similar substances, and rebound occurs at withdrawal. Menstrual cycle-linked disorders can be understood by the concept that they are caused by the action of endogenously produced GABA-steroids through three mechanisms: (a) direct action, (b) tolerance induction, and (c) withdrawal effect. Examples of symptoms and disorders caused by the direct action of GABA steroids are sedation, memory and learning disturbance, clumsiness, increased appetite, worsening of petit mal epilepsy, negative mood as tension, irritability and depression during hormone treatments, and the premenstrual dysphoric disorder (PMDD). A continuous exposure to GABA steroids causes tolerance, and women with PMDD are less sensitive to GABA-A modulators. A malfunctioning GABA-A receptor system is related to stress sensitivity, concentration difficulties, loss of impulse control, irritability, anxiety, and depression. An example of withdrawal effect is "catamenial epilepsy," when seizures increase during menstruation after the withdrawal of GABA steroids. Similar phenomena occur at stress since the adrenals produce GABA steroids during stress.

Affect↗