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PubMed2002

Intrauterine 10 microg and 20 microg levonorgestrel systems in postmenopausal women receiving oral oestrogen replacement therapy: clinical, endometrial and metabolic response.

OBJECTIVE: The clinical and endometrial efficacy and lipid response of two different doses of intrauterine levonorgestrel were assessed in comparison with sequential oral medroxyprogesterone acetate in postmenopausal women receiving continuous oral E2-valerate. DESIGN: One-year prospective multicentre randomised control trial. SETTING: Four outpatient clinics in Oulu, Helsinki and Jyväskylä, Finland. POPULATION: A total of 163 healthy volunteer postmenopausal women with climacteric complaints or already using hormone replacement therapy (HRT). INTERVENTIONS: Subjects were randomly allocated to receive a new intrauterine system releasing 10 microg of levonorgestrel daily or an established intrauterine system (Mirena) releasing 20 microg of levonorgestrel daily or sequential oral medroxyprogesterone acetate (5mg/day, 14/30 days). All three regimens were combined with an oral daily dose of 2mg of E2-valerate. MAIN OUTCOME MEASURES: Bleeding patterns were assessed by diaries kept by the subjects. Endometrial effects were evaluated by histologic biopsies taken at the baseline and after six and 12 months of therapy. Serum concentrations of total, HDL and LDL cholesterol, triglycerides and lipoprotein(a) were determined at the baseline and after six and 12 months of therapy. RESULTS: Insertion of the smaller 10 microg levonorgestrel system was easy in 70% and difficult in 4% and that of Mirena was easy in 46% and difficult in 21% of the subjects. After six months of therapy, 43 (95.6%) of the 47 subjects receiving 10 microg levonorgestrel and 54 (98.2%) of the 55 subjects receiving 20 microg levonorgestrel had no bleeding, while the sequential medroxyprogesterone acetate regimen produced typical cyclic withdrawal bleedings. Endometrial hyperplasia was not observed in any of the treatment groups during the 12-month study. After 12 months of therapy, strong endometrial suppression was found in 46/47 and 55/55 of the subjects receiving 10 microg and 20 microg of levonorgestrel, respectively, while the endometrium was proliferative in 18/47 of the subjects in the medroxyprogesterone acetate group. Serum total cholesterol decreased in all treatment groups. HDL cholesterol increased in women receiving medroxyprogesterone acetate or the smaller intrauterine dose of levonorgestrel. CONCLUSIONS: Both intrauterine doses of levonorgestrel provided good endometrial protection in postmenopausal women on oestrogen replacement therapy. The advantage of the 10 microg system with a smaller size is the easier insertion of the system and a minimal attenuation of the favourable effects of oral oestrogen on the serum lipid profile.

Administration, Intravaginal↗
PubMed1992

The hormonal regulation of platelet-activating factor-acetylhydrolase in the rat.

Platelet-activating factor-acetylhydrolase (PAF-AH), the enzyme that inactivates PAF, is decreased in the plasma of both rabbits and humans during the latter stages of pregnancy. The activity of the enzyme was decreased in rats by the administration of 1,3,5(10)-estratrien-17 alpha-ethynyl-3,17 beta-diol (17 alpha-ethynylestradiol) and increased by dexamethasone treatment. In the present study, we have further defined the hormonal regulation of PAF-AH levels in plasma of adult and juvenile rats. Estrone (E1), 17 beta-estradiol (E2), estriol (E3), and various progestins [4-pregnen-6 alpha-methyl-17 alpha-ol-3,20-dione (medroxyprogesterone), 4-estren-17 alpha-ethynyl-17 beta-ol-3-one (norethindrone), and 5(10)-estren-17 alpha-ethynyl-17 beta-ol-3-one (norethynodrel)] were administered to adult rats, and the plasma PAF-AH activities were assayed. E1, E2, and E3 administration to adult female rats lowered the plasma PAF-AH activity, E3 being the most effective. After administration of these estrogens the activity returned to the preinjection level within 4 days. The administration of medroxyprogesterone resulted in a 2-fold increase in plasma PAF-AH activity in adult female rats, and the activity remained elevated for up to 30 days. When adult male rats were treated with similar doses only a 20% increase was observed and the PAF-AH activity returned to control values by day 10. In contrast, norethindrone and norethynodrel administration resulted in a reduction of the enzyme activity in adult female rats. The plasma PAF-AH activity in juvenile male and female rats (3 weeks of age, 45-60 g body wt) was two times higher than that in adult rats of both sexes and spontaneously decreased up to the time of puberty. When juvenile male or female rats were injected with either 17 alpha-ethynylestradiol or medroxyprogesterone, a minimal change in PAF-AH activity was observed. In contrast, when dexamethasone was administered to juvenile male and female rats the plasma PAF-AH activity increased in a manner similar to adult animals. It is suggested that estrogens cause a decrease and medroxyprogesterone an increase in plasma PAF-AH activity. It is suggested that the different responsiveness to medroxyprogesterone between adult female and male rats and juvenile animals may depend on the concentration of the hormone receptor in the tissue responsible for the synthesis of PAF-AH. The decrease in PAF-AH activity after the administration of norethindrone and norethynodrel may be due to the known estrogenic activity of these steroids.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗
PubMed2003

Glycosaminoglycan profile in bladder and urethra of castrated rats treated with estrogen, progestogen, and raloxifene.

OBJECTIVE: This study was undertaken to evaluate the action of conjugated equine estrogens alone, medroxyprogesterone, the combination of these estrogens with progestogens, and of raloxifene on the glycosaminoglycan profile in the bladder and urethra of adult oophorectomized rats in comparison with noncastrated rats. STUDY DESIGN: Sixty adult rats, of which 50 were submitted to bilateral oophorectomy, were studied. After 4 days, the latter were assigned to five groups of 10 animals each. For 30 consecutive days the following treatments were given: group 1, conjugated equine estrogens; group 2, conjugated equine estrogens combined with medroxyprogesterone acetate; group 3, medroxyprogesterone; group 4, raloxifene; and group 5, placebo. Thereafter the bladders and urethras of the animals were removed, processed to yield a dry powder of which the sulfated glycosaminoglycan content was determined by densitometry after agarose gel electrophoresis and that of hyaluronic acid by a fluorimetric assay. RESULTS: Glycosaminoglycans found in the bladder and urethra were dermatan sulfate, heparan sulfate, and hyaluronic acid. In the bladder, hypoestrogenism or replacement with estrogens led to a lower sulfated glycosaminoglycan content. Replacement with estrogens and/or medroxyprogesterone reverted this effect. Hypoestrogenism decreased the dermatan sulfate/heparan sulfate ratio and reduced hyaluronic acid content. Estrogen therapy reverted this alteration and medroxyprogesterone addition annulled the estrogenic effect. In the urethra, castration did not alter hyaluronic acid content and sulfated glycosaminoglycan content, but raloxifene decreased the latter. CONCLUSION: Castrated rats had a decrease in sulfated glycosaminoglycans and hyaluronic acid content in the bladder. Hormonal replacement altered the quantity and quality of glycosaminoglycans. In the urethra, raloxifene reduced sulfated glycosaminoglycans.

Analysis of Variance↗
PubMed1991

Morphine, naloxone and the gonadotrophin surge in ewes.

Possible endogenous opioid peptide regulation of the preovulatory gonadotrophin surge was examined in ewes during the breeding season. Intact ewes (n = 54) were synchronized by treatment for 12 days with intravaginal sponges releasing medroxyprogesterone acetate. Luteinizing hormone (LH) and follicle-stimulating hormone (FSH) secretion prior to and during the gonadotrophin surge were not affected by naloxone (0.33 mg/kg body wt per h) administered from the time of medroxyprogesterone acetate withdrawal until 30 h after the onset of oestrus (n = 6). Morphine was administered in 4 patterns: (i) 0.25 mg morphine/kg body wt per h from medroxy-progesterone acetate withdrawal until 30 h after the onset of oestrus (n = 6), (ii) 0.25 mg morphine/kg body wt per h from 24 to 48 h after medroxyprogesterone acetate withdrawal (n = 6), (iii) 0.50 mg morphine/kg body wt per h from 24 to 36 h after medroxyprogesterone acetate withdrawal (n = 6) and (iv) 0.50 mg morphine/kg body wt per h from 18 to 30 h after medroxyprogesterone acetate withdrawal (n = 6). Oestrus and the gonadotrophin surge were delayed, but not blocked, in all cases of morphine administration (P less than 0.05). Inconsistent effects of morphine on circulating oestradiol and gonadotrophin concentrations prior to the gonadotrophin surge suggest that the delays are not due to reduced gonadotrophic support of ovarian oestradiol output. Morphine may reduce responsiveness of central behavioural and gonadotrophin surge-generating centres to the oestradiol signal. The absence of effects of naloxone on gonadotrophin secretion suggest that suppression of LH secretion by opioid peptide activity is reduced after the end of the luteal phase.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMedDate not supplied

[Breast histologic changes in female rats treated with sex steroids].

OBJECTIVE: To evaluate the association of histologic changes in the breasts of female rats undergoing therapy with sex steroids. METHODS: An experimental study was conducted of 40 castrated female non-pubertal rats, 20 had given birth (Group B) and 20 had no offspring (Group A). After four weeks, these rats were randomly allocated to subgroups: A1, A2, A3, A4, A5 and B1, B2, B3, B4, B5. Steroids were given to subgroups as follows: A1 and B1--estradiol benzoate; A2 and B2--medroxyprogesterone acetate; A3 and B3--estradiol benzoate and medroxyprogesterone acetate; A4 and B4--tibolone; A5 and B5--placebo. After 10 weeks of treatment, animals were sacrificed and their mammary glands were analyzed. Histologic parameters evaluated were: epithelial cell proliferation, epithelial cells with secretory activity; and cell atypia in terminal duct units and buds or terminal alveoli. The association between microscopic analysis and diverse therapeutic regimens were analyzed by calculating the odds ratio and its respective 95% confidence interval. RESULTS: Histologic changes were observed in 29 rats: moderate hyperplasia (52.5%), hyperplastic alveolar nodule (42.5%), epithelial atypia (35%), mild hyperplasia (32.5%), secretory activity (20%) and severe hyperplasia (5%). In rats with no offspring when compared to the control, 1.3 times more hyperplastic alveolar nodules were found in the group treated with estradiol, the same was true for moderate hyperplasia in the rats that received medroxyprogesterone acetate, hyperplastic alveolar nodules and epithelial atypia in the group treated with estradiol plus medroxyprogesterone acetate. In the rats with offspring 1.3 times more secretory activity was found with estradiol. CONCLUSION: Epithelial hyperplasia and epithelial atypia with no proliferation are strongly associated to combined therapy with estradiol plus medroxyprogesterone acetate, mainly in the rats without offspring.

Animals↗
PubMed1986

Biochemical and histologic effects of sequential estrogen/progestin therapy on the endometrium of postmenopausal women.

Medroxyprogesterone acetate in doses of 10, 5, and 2.5 mg was administered sequentially to three groups of postmenopausal women receiving 0.3 mg, 0.625 mg, and 1.25 mg of conjugated equine estrogens, respectively. Serial endometrial biopsies were performed on these women before therapy, during estrogen therapy alone, and during sequential estrogen-progestin therapy. Endometrial histology and estrogen receptor concentrations were assessed. A linear increase of cytosolic estrogen receptor concentration occurred over the dosage range of conjugated equine estrogen. When medroxyprogesterone acetate was added to the estrogen therapy, the concentrations of estrogen receptors fell. Within the groups of women receiving 0.3 mg and 0.625 mg of conjugated equine estrogen, all doses of medroxyprogesterone acetate were equally effective in reducing the levels of cytosolic receptor to pretreatment levels. However, at the conjugated equine estrogen dose of 1.25 mg, only 5 mg and 10 mg doses were effective in reducing the cytosolic receptor concentration to pretreatment levels. Histologically, little effect was observed from the lowest doses of either drug. However, even though 5 and 10 mg of medroxyprogesterone acetate were identical biochemically, the 10 mg dose was the only one producing a homogeneous, secretory pattern within the endometrium.

Biopsy↗
PubMed1982

Postoperative prophylactic use of progesterone in renal cell carcinoma.

Medroxyprogesterone acetate has been used prophylactically in 35 patients with stages I and IIIA renal cell carcinoma who had undergone radical nephrectomy. Metastasis was noted in 26 per cent (9 of 35) of the patients who had received the drug and in 44 per cent (20 of 45) of those who had not (controls). The incidence of metastasis in patients who had undergone nephrectomy more than 3 years previously was 10 per cent (3 of 31) for patients who received medroxyprogesterone acetate and 35 per cent (15 of 43) for the control group, the difference being statistically significant. Prognosis tended to be better in patients who had received medroxyprogesterone acetate than in the controls, and relative 3 and 5-year survival rates being 99.3 and 87.2 per cent, respectively, in the former group, and 86.8 and 75.0 per cent, respectively, in the latter group. There was no significant difference between these 2 groups. However, it may be concluded that prophylactic medroxyprogesterone acetate seems to be beneficial in the prevention of postoperative metastasis of renal cell carcinoma.

Adenocarcinoma↗
PubMed1991

Comparison of continuous versus sequential estrogen and progestin therapy in postmenopausal women.

A pilot study was performed comparing the efficacy and safety of continuous versus sequential schedules of the two most commonly prescribed medications for ovarian hormone replacement, conjugated equine estrogens and medroxyprogesterone acetate. Bleeding patterns, endometrial histology, and metabolic parameters were studied in 48 postmenopausal women prospectively randomized to a continuous schedule (daily estrogen and progestin) or a sequential schedule (conjugated estrogen on days 1-25, medroxyprogesterone acetate on days 16-25). Doses studied were 0.625 and 1.25 mg of conjugated estrogens and 10 mg of medroxyprogesterone acetate. Significantly greater bleeding was observed with the 1.25-mg dosage of conjugated estrogens. Bleeding patterns were similar between schedules, with the exception that amenorrhea was more prevalent in the women using the 1.25-mg dosage of estrogen and the continuous progestin schedule. More frequent endometrial atrophy was observed with the continuous schedule, supporting the concept that prolonged use of this schedule may promote amenorrhea in most patients. Both doses and schedules were associated with modest and insignificant increases in high-density lipoprotein cholesterol. Sequential therapy did not prevent the estrogen-induced decrease of low-density lipoprotein cholesterol, whereas the continuous schedule did, particularly with 0.625-mg dosage of conjugated estrogens. Significant increases of triglycerides were also seen with the continuous but not with the sequential schedule. Because of reports that the continuous schedule using the 2.5-mg dosage of medroxyprogesterone acetate does not elicit these actions on circulating lipids, attention should be directed toward examining the long-term effects of this lower dosage given continuously.

Drug Administration Schedule↗
PubMed1986

Oral progesterone treatment in chronic obstructive lung disease: failure of voluntary hyperventilation to predict response.

Previous studies have shown that some patients with chronic obstructive lung disease and hypercapnia will respond to medroxyprogesterone with improvement in arterial blood gases. The exact mechanism of this effect is unclear but it is presumed to be a result of ventilatory stimulation. To determine whether the ability to correct arterial blood gas abnormalities by voluntary hyperventilation would predict a subsequent favourable response to progesterone, we studied 11 subjects with chronic obstructive lung disease and chronic hypercapnia. Five subjects had chronic obstructive lung disease of moderate severity with mean (SE) FEV1 1.8 (0.34) 1 maximum voluntary ventilation (MVV) 40.4 (7.16) 1/min-1, arterial oxygen tension (Pao2) 53.8 (2.40 mm Hg, and arterial carbon dioxide tension Paco2) 49.6 (3.91) mm Hg, and were able to normalise their blood gas tensions during voluntary hyperventilation (Pao2 85.4 (8.01) mm Hg; Paco2 32.8 (3.43) mm Hg). Six subjects had severe chronic obstructive lung disease with FEV1 0.77 (0.12) 1, MVV 19 (3.09) 1/min-1, Pao2 60.0 (2.89) mm Hg and Paco2 50.5 (1.38) mm Hg, and they could not significantly alter their blood gases with voluntary hyperventilation (Pao2 62.5 (3.19) mm Hg, Paco2 49.7 (1.84) mm Hg). The groups were similar in age, height, weight, and resting Pao2 and Paco2. Each subject received one month of oral placebo and one month of medroxyprogesterone acetate (Provera). 20 mg orally thrice daily, given in a randomised, double blind fashion. The groups responded similarly with a significantly higher Pao2 and lower Paco2 while having medroxyprogesterone acetate than while having placebo. Two patients with polycythaemia showed a reduction in haemoglobin concentration while taking progesterone. It is concluded that the response to medroxyprogesterone is not predictable from spirometric or blood gas changes after voluntary hyperventilation.

Blood Gas Analysis↗
PubMed1987

Effects of prenatal administration of mestranol and two progestins on testosterone synthesis and reproductive tract development in male rats.

The oestrogen mestranol (0, 0.01, 0.1 mg/kg body weight per day) and the progestins medroxyprogesterone-acetate and norethisterone (0, 2, 20 mg/kg body weight per day each) in sesame oil were intubated intragastrically daily during gestational days 14.5 through 19.5 to pregnant rats. Males were studied as 20.5-day-old foetuses and 4-month-old adults for serum testosterone and LH concentrations, in vitro testosterone synthesis, anogenital distance (foetuses only) and testes, seminal vesicle and ventral prostate weights. Administration of 0.1 mg mestranol decreased by 35 to 70% basal and LH-stimulated testosterone synthesis by both foetal and adult testes in vitro (P less than 0.01). Foetal body weights (P less than 0.05), but not anogenital distances, were significantly decreased. Testosterone content in adult sera was reduced significantly (P less than 0.05) to less than 50% of control. Testes, ventral prostate, seminal vesicle and epididymal weights were unaffected by treatment. Medroxyprogesterone acetate or norethisterone administration did not alter testes endocrine function in foetal or adult offspring. In a small number of rats, pregnant for 10.5, 14.5 or 18.5 days, [3H]ethinyloestradiol was intubated and foetal and placental tissue examined for appearance and content of radioactivity. Radioactivity was detected in 10.5, 14.5 and 18.5 days old placentas, and 14.5 and 18.5 days old foetal liver, gonads and external genitalia. With [3H]medroxyprogesterone acetate, radioactivity was localized in 14.5 day placenta and foetal tissues. Thin-layer chromatographic analysis showed most of the activity to migrate as authentic ethinyloestradiol or medroxyprogesterone acetate. These results demonstrate inhibition of testicular testosterone synthesis by mestranol, presumably by being transferred across the placenta and acting in the foetus.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Menopausal hormone replacement therapy with continuous daily oral micronized estradiol and progesterone.

The safety and efficacy of a daily combination of micronized estradiol (E2) (0.7-1.05 mg) and progesterone (200-300 mg) were evaluated in ten menopausal women with moderate to severe vasomotor symptoms and/or vaginal atrophy over a 12-month study interval. For comparison, five similar women were placed on conjugated estrogens, 0.625 mg daily, and medroxyprogesterone acetate, 10 mg daily, for the first 10 days of each calendar month for 12 months. Patients were evaluated at 0, 1, 3, 6, and 12 months. Estrogens rose significantly from baseline in both groups (P less than .01). Progesterone increased significantly above baseline in the E2 and progesterone group (P less than .01), but did not change in the conjugated estrogens and medroxyprogesterone acetate users. All women on E2 and progesterone had a decrease in total cholesterol and an increase in high-density lipoprotein cholesterol from baseline (P less than .01). Those on conjugated estrogens and medroxyprogesterone acetate had no significant change from baseline in total cholesterol; however, they did have an increase in high-density lipoprotein cholesterol values (P less than .01). In the E2 and progesterone group, the endometrial histology became completely quiescent and there was no uterine bleeding after 6 months of observation. Four of five women on conjugated estrogens and medroxyprogesterone acetate continued regular withdrawal bleeding throughout the study period, but no endometrial hyperplasia was encountered. This study demonstrates that the daily administration of a combination of micronized E2 and progesterone results in symptomatic improvement, minimal side effects, an improved lipid profile, and amenorrhea without endometrial proliferation or hyperplasia in menopausal women.

Cholesterol↗
PubMed1981

Progesterone administration and progressive sleep apneas.

Nine adult patients with obstructive sleep apnea syndrome were administered medroxyprogesterone acetate, 60 to 120 mg/day, and the effect of medroxyprogesterone on clinical symptoms and obstructive apneas during sleep was assessed. Four patients responded with resolution of daytime sleepiness, disappearance of pedal edema, and a decrease in the number of obstructive apneas during sleep. Cessation of therapy led to a return of daytime sleepiness in three and an increase in obstructive apneas in all four subjects. Two responders experienced side effects of alopecia or decreased libido. Before medroxyprogesterone therapy, responders were distinguished from nonresponders only by the presence of a significantly lower resting arterial oxygen tension during wakefulness. We characterize a subgroup of patients who benefit from medroxyprogesterone therapy by reducing obstructive apneas during sleep.

Adult↗
PubMed1993

Hormonal regulation of platelet-activating factor-acetyltransferase activity in rat tissues.

Platelet-activating factor (PAF) plays a very important role in a number of physiological or pathological conditions. Recently, we and others have suggested that the PAF concentration in various tissues may be regulated by the enzyme that inactivates PAF, PAF acetylhydrolase (PAF-AH). Furthermore, it has been shown that the plasma isozyme of PAF-AH is regulated by various steroid hormone. Lyso-PAF:acetyl-CoA acetyltransferase (PAF-AT) is a key enzyme in PAF biosynthesis by the remodeling pathway. In the present study, the hormonal effects on the tissue levels of PAF-AT activity were investigated in various organs of the rat. The microsomal fraction was prepared from the spleen, lung, uterus, and liver of female rats which had been pretreated with dexamethasone, 17 alpha-ethynylestradiol, medroxyprogesterone-acetate, or vehicle and the PAF-AT activity was assayed. The rats treated with dexamethasone demonstrated significantly lower PAF-AT specific activity in the liver (P < 0.001) and spleen (P < 0.01), compared to the control group. A dose-dependent decrease of PAF-AT specific activity was demonstrated following dexamethasone treatment. Medroxyprogesterone injection also caused a significant decrease of PAF-AT activity in the liver (P < 0.01). No change of PAF-AT activity in any tissue was observed in the 17 alpha-ethynylestradiol-injected animals. Plasma PAF-AH activity was increased significantly by the administration of dexamethasone (P < 0.001) or medroxyprogesterone (P < 0.001), and decreased by 17 alpha-ethynylestradiol (P < 0.001), as previously described. The observation that dexamethasone or medroxyprogesterone treatment decreases the activity of PAF-AT and increases the plasma PAF-AH activity provides a mechanism for the tight control of PAF in tissues.

Acetyltransferases↗
PubMed1998

Symptom relief and side effects of postmenopausal hormones: results from the Postmenopausal Estrogen/Progestin Interventions Trial.

OBJECTIVE: To assess pair-wise differences between placebo, estrogen, and each of three estrogen-progestin regimens on selected symptoms. METHODS: This was a 3-year, multicenter, double-blind, placebo-controlled trial in 875 postmenopausal women aged 45-64 years at baseline. Participants were assigned randomly to one of five groups: 1) placebo, 2) daily conjugated equine estrogens, 3) conjugated equine estrogens plus cyclical medroxyprogesterone acetate, 4) conjugated equine estrogens plus daily medroxyprogesterone acetate, and 5) conjugated equine estrogens plus cyclical micronized progesterone. Symptoms were self-reported using a checklist at 1 and 3 years. Factor analysis reduced 52 symptoms to a set of six symptom groups. RESULTS: In intention-to-treat analyses at 1 year, each active treatment demonstrated a marked, statistically significant, protective effect against vasomotor symptoms compared with placebo (odds ratios [ORs] 0.17-0.28); there was no additional benefit of estrogen-progestin over estrogen alone. Only progestin-containing regimens were significantly associated with higher levels of breast discomfort (OR 1.92-2.27). Compared with placebo, women randomized to conjugated equine estrogens reported no increase in perceived weight. Those randomized to medroxyprogesterone acetate reported less perceived weight gain (OR 0.61-0.69) than placebo. Anxiety, cognitive, and affective symptoms did not differ by treatment assignment. Analyses restricted to adherent women were not materially different than those using intention-to-treat, except that women adherent to medroxyprogesterone acetate and micronized progesterone regimens reported fewer musculoskeletal symptoms (OR 0.62-0.68). CONCLUSION: These results confirm the usefulness of post-menopausal hormone therapy for hot flashes, show convincingly that estrogen plus progestin causes breast discomfort, and demonstrate little influence of postmenopausal hormones on anxiety, cognition, or affect.

Double-Blind Method↗
PubMed2000

The fibre dimensions of uterine smooth muscle of the rabbit following treatment by female sex steroids.

The effects of female sex hormones on the dimensions of myometrial smooth muscle fibres were studied by using ovariectomized rabbits. After one month of treatment, the fiber dimensions of the outer myometrial layer were measured, using cryostat sections. Calculated smooth muscle fiber volume was found to be in the sequence: control < medroxyprogesterone < estradiol < estradiol + medroxyprogesterone < estradiol alone. The measurements show that medroxyprogesterone-treated uteri contain the narrowest and the longest smooth muscle fibres, while estradiol treatment have the largest cells. This study complements previous observations in showing that medroxyprogesterone alone, or in combination with other modulators, contributes to sustain pregnancy by increasing internal resistance of estradiol-primed myometrial smooth muscle fiber fascicles. Our discussion, based on recent literature, shows that this resistance is ultimately controlled by changes in the myometrium innervation, in the repression of some controlling myofibrillar components, in the expression of specific membrane receptors and ionic channels, and in favoring the switching of molecular connexins in gap junctions, making P paramount in maintaining pregnancy. Moreover, other recent observations have also shown that probably an hcG-like hormone actually control P receptors expression in myometrial smooth muscles.

Animals↗
PubMed2000

Effects of estrogen replacement on the progression of coronary-artery atherosclerosis.

BACKGROUND: Heart disease is a major cause of illness and death in women. To understand better the role of estrogen in the treatment and prevention of heart disease, more information is needed about its effects on coronary atherosclerosis and the extent to which concomitant progestin therapy may modify these effects. METHODS: We randomly assigned a total of 309 women with angiographically verified coronary disease to receive 0.625 mg of conjugated estrogen per day, 0.625 mg of conjugated estrogen plus 2.5 mg of medroxyprogesterone acetate per day, or placebo. The women were followed for a mean (+/-SD) of 3.2+/-0.6 years. Base-line and follow-up coronary angiograms were analyzed by quantitative coronary angiography. RESULTS: Estrogen and estrogen plus medroxyprogesterone acetate produced significant reductions in low-density lipoprotein cholesterol levels (9.4 percent and 16.5 percent, respectively) and significant increases in high-density lipoprotein cholesterol levels (18.8 percent and 14.2 percent, respectively); however, neither treatment altered the progression of coronary atherosclerosis. After adjustment for measurements at base line, the mean (+/-SE) minimal coronary-artery diameters at follow-up were 1.87+/-0.02 mm, 1.84+/-0.02 mm, and 1.87+/-0.02 mm in women assigned to estrogen, estrogen plus medroxyprogesterone acetate, and placebo, respectively. The differences between the values for the two active-treatment groups and the value for the placebo group were not significant. Analyses of several secondary angiographic outcomes and subgroups of women produced similar results. The rates of clinical cardiovascular events were also similar among the treatment groups. CONCLUSIONS: Neither estrogen alone nor estrogen plus medroxyprogesterone acetate affected the progression of coronary atherosclerosis in women with established disease. These results suggest that such women should not use estrogen replacement with an expectation of cardiovascular benefit.

Adult↗
PubMed2003

Hormone therapy and the progression of coronary-artery atherosclerosis in postmenopausal women.

BACKGROUND: In postmenopausal women with coronary artery disease, conjugated equine estrogen with or without continuous administration of medroxyprogesterone acetate has failed to slow the progression of atherosclerosis. Whether 17beta-estradiol (the endogenous estrogen molecule) alone or administered sequentially with medroxyprogesterone acetate can slow the progression of atherosclerosis is unknown. METHODS: We conducted a double-blind, placebo-controlled trial in 226 postmenopausal women (mean age, 63.5 years) who had at least one coronary-artery lesion. Participants were randomly assigned to usual care (control group), estrogen therapy with micronized 17beta-estradiol alone (estrogen group), or 17beta-estradiol plus sequentially administered medroxyprogesterone acetate (estrogen-progestin group). In all patients the low-density lipoprotein (LDL) cholesterol level was reduced to a target of less than 130 mg per deciliter. The primary outcome was the average per-participant change between base-line and follow-up coronary angiograms in the percent stenosis measured by quantitative coronary angiography. RESULTS: After a median of 3.3 years of follow-up, the mean (+/-SE) change in the percent stenosis in the 169 participants who had a pair of matched angiograms was 1.89+/-0.78 percentage points in the control group, 2.18+/-0.76 in the estrogen group, and 1.24+/-0.80 in the estrogen-progestin group (P=0.66 for the comparison among the three groups). The mean difference in the percent stenosis between the estrogen group and the control group was 0.29 percentage point (95 percent confidence interval, -1.88 to 2.46), and the mean difference between the estrogen-progestin group and the control group was -0.65 (95 percent confidence interval, -2.87 to 1.57). CONCLUSIONS: In older postmenopausal women with established coronary-artery atherosclerosis, 17beta-estradiol either alone or with sequentially administered medroxyprogesterone acetate had no significant effect on the progression of atherosclerosis.

Coronary Angiography↗
PubMed2003

Contrasting effects of two hormone replacement therapies on the cardiovascular and mammary gland outcomes in surgically postmenopausal monkeys.

OBJECTIVE: The purpose of this study was to compare the effects of two hormone replacement therapies on the intermediate end points of coronary heart disease and mammary gland hyperplasia in postmenopausal monkeys. STUDY DESIGN: Surgically postmenopausal cynomolgus monkeys were fed an atherogenic diet for 12 months while receiving no treatment (control, n = 19), conjugated equine estrogens plus continuous medroxyprogesterone acetate (n = 19), or ethinyl estradiol plus norethindrone acetate (n = 21) at doses that were scaled from those doses taken by women. RESULTS: Quantitative coronary angiography revealed that the arteries of the control group and the conjugated equine estrogens plus continuous medroxyprogesterone acetate-treated animals constricted in response to acetylcholine (-5.4% +/- 1.4% and -6.2% +/- 1.5%, respectively), whereas those arteries in the animals in the ethinyl estradiol plus norethindrone acetate group did not (P =.002). The incidence of dobutamine-induced ST-segment depression in the ethinyl estradiol plus norethindrone acetate group (10.5%) was significantly less than in the control group (68.8%, P =.001) or the conjugated equine estrogens plus continuous medroxyprogesterone acetate group (50%, P =.01). Conjugated equine estrogens plus continuous medroxyprogesterone acetate, but not ethinyl estradiol plus norethindrone acetate, induced diffuse epithelial tissue proliferation in the mammary glands (P =.0006). CONCLUSION: Ethinyl estradiol plus norethindrone acetate protected against atherosclerosis-induced endothelium-mediated vasoconstriction of coronary arteries and heart rate-induced myocardial ischemia and did not induce epithelial tissue proliferation (tissue density) in the mammary gland.

Animals↗