Oelkers W, Berger V, Bolik A, Bähr V, Hazard B, Beier S, Elger W, Heithecker A
Department of Internal Medicine, Klinikum Steglitz, Freie Universitat Berlin, Germany.
J Clin Endocrinol Metab. 1991 Oct;73(4):837-42. doi: 10.1210/jcem-73-4-837.
Dihydrospirorenone (DHSP; 6 beta,7 beta,15 beta,16 beta-dimethylen-3-oxo-17- alpha-pregn-4-en-21,17-carbolacton) is an aldosterone antagonist 8 times as potent as spironolactone in the rat. It is also a progestogen that suppresses ovulation in normal women at a daily dosage of 2 mg. The effects of this dosage on the renin-aldosterone system and sodium and potassium balances were investigated in two experiments. In study I, 12 healthy women received a diet with 100 mmol sodium and 60-70 mmol potassium per day from days 3-13 of their normal menstrual cycles. Six women took 2 mg DHSP; 6 others received placebo from days 8-13 of the cycle. Sodium excretion in the DHSP group rose from a mean of 79 to 98.5 +/- 8.3 mmol/day during medication. Placebo had no effect. The difference between average sodium excretion rates in subjects treated with DHSP or placebo was close to significance (P = 0.053). Potassium excretion did not change. Weight loss was slightly greater after DHSP than placebo treatment. PRA and plasma and urinary aldosterone rose significantly during DHSP medication. In study II, 12 women on a free diet were studied during a control and a treatment cyle. From days 5-25 of the second cycle, they took 2 mg DHSP (n = 6) or 1 mg cyproterone acetate. Both compounds suppressed ovulation and the rise in progesterone. During cycle 1, sodium excretion, PRA, and aldosterone were higher in the luteal than in the follicular phase, probably due to an antialdosterone effect of progesterone. DHSP reversed this pattern of natriuresis by inducing a significant early natriuresis and a rise in PRA and aldosterone. Cyproterone acetate only abolished differences in natriuresis between the follicular and luteal phases and the rise of PRA and plasma aldosterone in the luteal phase. We conclude that DHSP may be a suitable partner of ethinyl estradiol as a constituent of an oral contraceptive, since its progestogenic and antialdosterone profile is similar to that of progesterone. Other synthetic progestogens are devoid of an antialdosterone effect. The antialdosterone effect of DHSP may help prevent sodium retention and a rise in blood pressure in susceptible women.
二氢螺内酯（DHSP；6β,7β,15β,16β - 二亚甲基 - 3 - 氧代 - 17α - 孕甾 - 4 - 烯 - 21,17 - 碳内酯）是一种醛固酮拮抗剂，在大鼠体内的效力是螺内酯的8倍。它也是一种孕激素，每日剂量为2mg时可抑制正常女性排卵。在两项实验中研究了该剂量对肾素 - 醛固酮系统以及钠和钾平衡的影响。在研究I中，12名健康女性在正常月经周期的第3 - 13天接受每天含100mmol钠和60 - 70mmol钾的饮食。6名女性服用2mg DHSP；另外6名在月经周期的第8 - 13天接受安慰剂。服药期间，DHSP组的钠排泄量从平均79mmol/天升至98.5±8.3mmol/天。安慰剂无效果。接受DHSP或安慰剂治疗的受试者平均钠排泄率之间的差异接近显著水平（P = 0.053）。钾排泄量未改变。DHSP治疗后的体重减轻略大于安慰剂治疗。服用DHSP期间，血浆肾素活性（PRA）、血浆和尿醛固酮显著升高。在研究II中，对12名自由饮食的女性在对照周期和治疗周期进行了研究。在第二个周期的第5 - 25天，她们服用2mg DHSP（n = 6）或1mg醋酸环丙孕酮。两种化合物均抑制排卵和孕酮升高。在周期1中，黄体期的钠排泄、PRA和醛固酮高于卵泡期，这可能是由于孕酮的抗醛固酮作用。DHSP通过诱导显著的早期钠排泄以及PRA和醛固酮升高，逆转了这种利钠模式。醋酸环丙孕酮仅消除了卵泡期和黄体期之间利钠的差异以及黄体期PRA和血浆醛固酮的升高。我们得出结论，DHSP作为口服避孕药的成分，可能是炔雌醇的合适配伍药物，因为其孕激素和抗醛固酮特性与孕酮相似。其他合成孕激素没有抗醛固酮作用。DHSP的抗醛固酮作用可能有助于预防易感女性的钠潴留和血压升高。
