Potassium-magnesium citrate is an effective prophylaxis against recurrent calcium oxalate nephrolithiasis.

PURPOSE: We examined the efficacy of potassium-magnesium citrate in preventing recurrent calcium oxalate kidney calculi. MATERIALS AND METHODS: We conducted a prospective double-blind study of 64 patients who were randomly assigned to receive placebo or potassium-magnesium citrate (42 mEq. potassium, 21 mEq. magnesium, and 63 mEq. citrate) daily for up to 3 years. RESULTS. New calculi formed in 63.6% of subjects receiving placebo and in 12.9% of subjects receiving potassium-magnesium citrate. When compared with placebo, the relative risk of treatment failure for potassium-magnesium citrate was 0.16 (95% confidence interval 0.05 to 0.46). Potassium-magnesium citrate had a statistically significant effect (relative risk 0.10, 95% confidence interval 0.03 to 0.36) even after adjustment for possible confounders, including age, pretreatment calculous event rate and urinary biochemical abnormalities. CONCLUSIONS: Potassium-magnesium citrate effectively prevents recurrent calcium oxalate stones, and this treatment given for up to 3 years reduces risk of recurrence by 85%.

Comparison of endometrial growth produced by unopposed conjugated estrogens or by micronized estradiol in postmenopausal women.

OBJECTIVE: When unopposed estrogen replacement treatment is used, what is the pattern of endometrial growth? Does endometrial growth differ for various dosages and formulations? STUDY DESIGN: A total of 87 postmenopausal women, median age 57 years (mean 56.7 +/- 5.6 years, range 45 to 69 years), were studied in a prospective, randomized, open clinical trial lasting 24 weeks. The treatment arms consisted of micronized estradiol, 0.5 or 1.0 mg (Estrace, Bristol-Myers Squibb, Princeton, N.J.), and conjugated estrogens, 0.625 mg (Premarin, Wyeth-Ayerst, Philadelphia). Endometrial thickness was evaluated by vaginal probe ultrasonography at outset and after 6, 12, and 24 weeks of treatment. RESULTS: Endometrial growth was progressive over time; more than half the total 24-week growth occurred in the first 6 weeks. The mean weekly rate (+/-SD) of endometrial growth was similar for micronized estradiol, 1.0 mg, and conjugated estrogens, 0.625 mg (0.19 +/- 0.15 mm for micronized estradiol, 1.0 mg, and 0.19 +/- 0.14 mm for conjugated estrogens, 0.625 mg). These rates differed to a statistically significant degree (p < 0.05) from the growth rate produced by micronized estradiol, 0.5 mg (0.08 +/- 0.16 mm). Both unscheduled and scheduled uterine bleeding was less likely among women using micronized estradiol, 0.5 mg, than among women using micronized estradiol, 1.0 mg, or conjugated estrogens, 0.625 mg. CONCLUSIONS: In a 24-week trial the therapeutically equivalent estrogen doses produced the same mean increment in endometrial thickness, but half-strength estradiol produced half as much endometrial growth.

Randomized controlled trial of a low animal protein, high fiber diet in the prevention of recurrent calcium oxalate kidney stones.

Low protein diets are commonly prescribed for patients with idiopathic calcium nephrolithiasis, who account for > 80% of new diagnoses of kidney stones. This dietary advice is supported by metabolic studies and epidemiologic observational studies but has not been evaluated in a controlled trial. Using 1983-1985 data from three Northern California Kaiser Permanente Medical Centers, the authors randomly assigned 99 persons who had calcium oxalate stones for the first time to a low animal protein, high fiber diet that contained approximately 56-64 g daily of protein, 75 mg daily of purine (primarily from animal protein and legumes), one-fourth cup of wheat bran supplement, and fruits and vegetables. Intervention subjects were also instructed to drink six to eight glasses of liquid daily and to maintain adequate calcium intake from dairy products or calcium supplements. Control subjects were instructed only on fluid intake and adequate calcium intake. Both groups were followed regularly for up to 4.5 years with food frequency questionnaires, serum and urine chemistry analysis, and abdominal radiography; and they were urged to comply with dietary instructions. In the intervention group of 50 subjects, stones recurred in 12 (7.1 per 100 person-years) compared with two (1.2 per 100 person-years) in the control group; both groups received a mean of 3.4 person-years of follow-up (p = 0.006). After adjustment for possible confounding effects of age, sex, education, and baseline protein and fluid intake, the relative risk of a recurrent stone in the intervention group was 5.6 (95% confidence interval 1.2-26.1) compared with the control group. The authors conclude that advice to follow a low animal protein, high fiber, high fluid diet has no advantage over advice to increase fluid intake alone.

Prevalence of hypothalamic-pituitary imaging abnormalities in impotent men with secondary hypogonadism.

PURPOSE: Because prevalence of structural lesions of the pituitary and hypothalamus in impotent men with secondary hypogonadism was undefined, we evaluated 164 men 27 to 79 years old whose chief complaint was erectile dysfunction and who repeatedly had low serum testosterone levels (less than 230 ng./dl.). MATERIALS AND METHODS: With computerized tomography or magnetic resonance imaging of the sella we detected potentially serious lesions (pituitary lesions greater than 5 mm. or any hypothalamic lesion) in 11 men (6.7%, 95% confidence interval 2.9 to 10.5%), including 5 pituitary microadenomas (5 mm. or larger), 4 pituitary macroadenomas and 2 hypothalamic lesions. RESULTS: Mean serum testosterone was lower in patients with (121 +/- 66 ng./dl., standard deviation) than without (177 +/- 39 ng./dl.) hypothalamic or pituitary imaging abnormalities (p < 0.001). For every 10 ng./dl. decrease in testosterone the risk of hypothalamic or pituitary imaging abnormalities increased 1.2-fold (p < 0.005). Macroadenomas and hypothalamic lesions were confined to 6 subjects with testosterone levels of 104 ng./dl. or less. CONCLUSIONS: The risk of hypothalamic or pituitary imaging abnormalities is low among men evaluated for erectile dysfunction and secondary hypogonadism. However, this risk increases markedly when the serum testosterone level is markedly decreased.

Spinal bone mineral loss in estrogen-replete, calcium-replete premenopausal women.

After peak bone mass in women is attained, the benefits of increased dietary calcium or supplemental calcium are uncertain. In a longitudinal, 4-year study we have investigated the effect of calcium intake on bone mineral in a group of 41 premenopausal women, aged 38-42 years at entry. Skeletal density was measured four times during the 4-year follow-up; spinal trabecular bone density (STBD) was measured by quantitative computed tomography, and midradius bone mineral density (RBMD) was measured by single photon absorptiometry. At baseline, no differences in bone density were observed among subjects in the highest and lowest quartiles of habitual dietary intake. Overall, STBD declined -0.86 +/- 0.15% per year (p < 0.001), but RBMD did not decline. Total calcium intake (dietary calcium plus supplemental calcium) did not correlate with the rate of STBD loss. Serum estradiol level did not decrease during the study, and bone loss did not correlate with the mean estradiol level. We conclude that premenopausal women in the fifth decade lose about 1% of spinal trabecular mineral yearly, in spite of a normal serum estradiol level and ample calcium intake.

Cyclic hormone replacement therapy using quarterly progestin.

OBJECTIVES: To determine whether cyclic progestin, when part of postmenopausal hormone replacement therapy, can be used quarterly instead of monthly without increasing the risk of endometrial hyperplasia. In addition, we determined whether this hormone replacement therapy regimen produces an acceptable menstrual pattern. METHODS: The subjects were 214 postmenopausal women, mean (+/- standard deviation) age 56.2 +/- 5.4 years, who had regularly used hormone replacement therapy (consisting of Premarin 0.625 mg/day with monthly cyclic medroxyprogesterone, 5 or 10 mg) for a mean of 5.4 +/- 4.5 years (minimum 1 year). The study intervention consisted of changing the subjects' treatment from the usual monthly progestin to four 3-month (ie, quarterly) cycles of medroxyprogesterone, 10 mg/day for 14 days. Endometrial histology was evaluated by doing endometrial biopsies at study outset and after 1 year. Scheduled and unscheduled vaginal bleeding was reported in daily diaries. RESULTS: Endometrial hyperplasia was found in 1.5% of 199 women completing follow-up, a rate similar to the 0.9% prevalence found at baseline. Compared with monthly medroxyprogesterone, quarterly medroxyprogesterone resulted in longer menses (7.7 +/- 2.9 versus 5.4 +/- 2.0 days) and more reports of heavy menses (31.1 versus 8.0%) and unscheduled bleeding (15.5 versus 6.8%). Despite these problems, women preferred the quarterly regimen by nearly four to one. CONCLUSIONS: In a 1-year trial, quarterly medroxyprogesterone appeared as safe as monthly medroxyprogesterone and was preferred by most women. This schedule may be useful for women seeking relief from monthly use of progestin and monthly menses.

Gynecologic complications of cyclic estrogen progestin therapy.

We evaluated the long-term gynecologic risks of postmenopausal estrogen therapy in conjunction with cyclic, monthly progestin (progestin-estrogen replacement therapy, or PERT). Our medical record review showed that incidence of abnormal vaginal bleeding necessitating gynecologic procedures for evaluation was significantly higher (RR, 3.1; 95% CI, 2.1-4.5), as was the rate of endometrial biopsy (RR, 3.4; 95% CI, 2.3-5.1), among women receiving PERT than among women not receiving hormone therapy. We also identified a non-significant trend toward a higher rate of dilation and curettage (RR, 1.5; CI, 0.7-3.3) among women receiving PERT. However, rates of endometrial hyperplasia and hysterectomy were similarly low in both groups. PERT apparently protects women against these serious gynecologic consequences previously seen in women taking unopposed estrogen.

Chlorthalidone reduces calcium oxalate calculous recurrence but magnesium hydroxide does not.

We examined the effectiveness of chlorthalidone or magnesium hydroxide in the prevention of recurrent calcium oxalate kidney calculi. In a double-blind random allocation design daily dosages of 25 or 50 mg. chlorthalidone, 650 or 1,300 mg. magnesium hydroxide, or an identical placebo were administered. All groups showed significantly decreased calculous events compared to the pretreatment rates. During the trial 56.1 per cent fewer calculi than predicted developed in the placebo group (p less than 0.01), whereas the groups receiving low and high dosage magnesium hydroxide showed 73.9 and 62.3 per cent fewer calculi, respectively (p less than 0.001 and less than 0.01, respectively). Chlorthalidone treatment resulted in a 90.1 per cent decrease from predicted rates and both dosages yielded similar results. When the treatments were compared chlorthalidone was significantly better than the placebo or magnesium hydroxide (p less than 0.01). The large decreases in calculous events seen when placebo or ineffective therapy was given underscore the positive treatment bias that occurs when historical controls are used and they demonstrate the need for proper experimental design.

Randomized trial of allopurinol in the prevention of calcium oxalate calculi.

In a double-blind study, we examined the efficacy of allopurinol in the prevention of recurrent calcium oxalate calculi of the kidney. Sixty patients with hyperuricosuria and normocalciuria who had a history of calculi were randomly assigned to receive either allopurinol (100 mg three times daily) or a placebo. After the study, the placebo group had 63.4 percent fewer calculi (P less than 0.001), whereas the allopurinol group had 81.2 percent fewer calculi (P less than 0.001). During the study period, the mean rate of calculous events was 0.26 per patient per year in the placebo group and 0.12 in the allopurinol group. When the treatment groups were compared by actuarial analysis, the allopurinol group was found to have a significantly longer time before recurrence of calculi (P less than 0.02). We conclude that allopurinol is effective in the prevention of calcium oxalate stones in patients with hyperuricosuria. The large reduction in the frequency of calculi in the placebo group underscores the positive treatment bias that regularly occurs in trials of prophylaxis against renal calculi when historical controls are used.