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Effect of paramethasone acetate on ovarian steroids and gonadotropins. I. Normal menstrual cycle.

In an attempt to elucidate the effect of paramethasone acetate on the hormonal profile of the normal menstrual cycle, 5 clinically healthy women, aged 24-36 yr, with ovulatory cycles were studied during a control menstrual cycle and during treatment with paramethasone acetate (6 mg/day). The length of the untreated cycle was 29.2 +/- 2.3 days as compared to 29.0 +/- 3.1 days during the paramethasone-treated cycle. Peak plasma E-2 level was 188.2 +/- 42.1 pg/ml in the control cycle and 74.4 +/- 15.3 pg/ml during paramethasone treatment (P is less than 0.05). Peak plasma 17 OH-P was 4.0 +/- 0.4 ng/ml in the control cycle and 1.6 +/- 0.2 ng/ml during the paramethasone treated cycle (P is less than 0.005). No significant differences in plasma progesterone were observed during the luteal phase of both cycles. Minimal and scattered differences were observed in plasma FSH. However, plasma LH levels were lower in the paramethasone acetate than in the control cycle almost throughout the entire period of study. Furthermore, midcycle LH peak in the control cycle was 958 +/- 104 ng/ml as compared to 283 +/- 24 ng/ml during the paramethasone treatment (P is less than 0.005). Despite these differences, ovulation occurred during paramethasone treatment based upon the observed rise in BBT, the plasma progesterone levels above 6 ng/ml and the secretory changes in the endometrium. These results suggest that: 1) Paramethasone may block E-2 synthesis at the ovarian level and , 2) Ovulation may still occur even in the presence of E-2 and LH plasma concentrations lower than those occurring in the normal menstrual cycle.

Adult

[Effect of high dosis of D-penicillamine and paramethasone on mechanical properties of rat connective tissue (author's transl)].

Male albino rats are treated with high doses of D-penicillamine (2000 mg/kg/day orally), paramethasone (50 mu-g/kg/day orally), and with a combination of equal doses of D-penicillamine and paramethasone for a period of 4 weeks. At the end of treatment the mechanical properties of dorsal skin and aorta of the experimental animals are determined. 4 weeks of treatment with D-penicillamine or paramethasone, respectively, leads to a decrease in the skin thickness of the experimental animals. With simultaneous administration of both substances the decrease in skin thickness is about the same. Load resulting in rupture is considerably reduced by D-penicillamine, while only a slight decrease is seen with paramethasone. Simultaneous administration of both substances results in considerable decrease in load resulting in rupture, similar to the effect produced by D-penicillamine. Tensile strength which is not influenced by paramethasone treatment, decreases after treatment with D-penicillamine as well as after simultaneous administration of D-penicillamin and paramethasone. Load resulting in rupture of the aorta remains uninfluenced under the experimental conditions. Comparison of the groups shows that simultaneous administration of D-penicillamine and paramethasone leads to the same results as those which may be obtained with sole administration of D-penicillamine. This suggests that the effect of D-penicillamine on the mechanical properties of the rat skin is not influenced by an additional high dose of paramethasone under the experimental conditions chosen.

Animals

Paramethasone acetate (PA): corticosteroid potency vs hypothalamic pituitary-gonadal axis.

Because paramethasone acetate (PA) suppresses basal and midcycle LH surge and blocks estrogen synthesis in the female, its possible effect upon testicular physiology was evaluated in 13 healthy men by measuring the circulating levels of FSH, LH, prolactin (PRL), testosterone (T), dihydrotestosterone (DHT), androstenedione (A), estradiol (E2) and cortisol (C) every 4 h throughout the day, before (control) and after PA (6 mg/d/7 d). The total concentrations of each hormone, as well as the PA-induced suppressibility (measured as percent decrease in the mean 24 h plasma level) were analyzed. PA suppressed neither the basal nor circadian rhythm of T and had no effect on LH, FSH or PRL output. DHT, A, E2 were significantly reduced and the basal concentrations and circadian variations of C were abolished. PA showed a dual control on the pituitary gonadal axis and while causing a maximal suppressed adrenocortical activity it had no interference in testosterone synthesis.

Adult

Effect of paramethasone acetate on women with secondary amenorrhea: a preliminary report.

Twelve women of normal weight (ages 17 to 36 years) with scanty menstrual bleeding were studied. They had no signs of virilization, gynecologic or endocrine pathology, or past history of hormonal treatment. Five women (group 1) experienced withdrawal bleeding after a 3-day course of chlormadinone acetate (2 mg/day) and the other seven did not (group 2). Daily venous blood samples were obtained 10 to 15 days afterward for 5 consecutive days of no treatment (control period) and during the next 5 days while the women received paramethasone acetate (PA), 2 mg/day (treatment period). In each plasma sample the concentrations of 17beta-estradiol (E2) and luteinizing hormone (LH; LER-907) were determined. The mean plasma E2 levels in group 1 were 35 +/- 8 and 86 +/- 10 pg/ml during the control and treatment periods, respectively (P less than 0.001), and the mean plasma LH levels were 28 +/- 6 and 94 +/- 34 ng/ml, respectively (P less than 0.001). No significant changes in plasma E2 and LH levels were observed in group 2 in either period. During the control period, the plasma E2 level in group 2 (14 +/- 2 pg/ml) was lower than that in group 1 (P less than 0.01); however, plasma LH levels were similar in both groups. The administration of PA for 5 months induced monthly ovulation in group 1 but not in group 2. These data suggest that the best results are obtained in women with optimal pretreatment levels of plasma E2.

Adolescent