Jessie Marmorston

Clinical Studies of Long-Term Estrogen Therapy in Men with Myocardial Infarction

Conclusions and summary 1. In a clinical trial men with coronary artery disease who had recovered from a frank myocardial infarction were randomly treated with Lynoral (ethinyl estradiol), Anvene, Premarin, or a placebo. The 3 estrogen preparations were used in small well-tolerated doses of comparable potency as indicated by mild breast tenderness. 2. No untoward effects of the treatment were observed in up to 60 months of continuous treatment. Changes in libido were rarely noted. 3. Premarin therapy significantly improved survival, particularly in the first 2 years of treatment. Lynoral (ethinyl estradiol) and Anvene had no effect on survival as compared with placebo treatment. 4. Subclasses of patients most likely to benefit from Premarin therapy were those with relatively poor initial prognosis: men under age 55, who had had a first myocardial infarction, and with complications of arteriosclerotic heart disease present. 5. Lynoral (ethinyl estradiol) and Anvene significantly lowered the cholesterol-phospholipid ratio. Premarin had no such effect. 6. There is no necessary correlation between physical response (e.g., breast tenderness), serum lipid and survival effects of estrogen preparations in the male recovering from myocardial infarction: altering of the serum lipids does not necessarily improve survival, and survival may be improved without altering of the serum lipids.

II. Urinary excretion of estrone, estradiol, and estriol by patients with breast cancer and benign breast disease

The levels of estrogen fractions excreted by patients with breast cancer or benign breast disease are discussed. Urinary estrogen metabolites are an indirect measure of steroids circulating in the vascular system and contained in the hormonal environment. 113 women 55 premenopausal and 58 postmenopausal were studied. Urine specimens from premenopausal women were collected at about Day 10 or Day 20 of the menstrual cycles but no significant difference was found between levels excreted during follicular or luteal phases. Urinary estrone estradiol and estriol fractions were separated chemically and quantified by bioassay. Postmenopausal patients with breast cancer were found to excrete significantly higher levels of estriol and total estrogen than others. In premenopausal women with breast cancer or with benign breast disease the estriol fraction represented a significantly higher proportion of the total estrogen than in control groups.

Hormone Excretion Patterns in Breast and Prostate Cancer Are Abnormal

In patients with breast and prostate cancer hormone excretion patterns differ in a similar way from patterns in persons without cancer.

The collagen and hexosamine content of the skin of normal and experimentally treated rats

Abstract The collagen and hexosamine contents of the skin of growing rats were determined. Regression equations were derived upon the basis that there is a linear relationship between the logarithm of body weight and logarithm collagen, logarithm body weight and logarithm hexosamine, logarithm body area and logarithm collagen, and logarithm body area and logarithm hexosamine. The collagen content of the skin increases much more rapidly than the increase in weight. The hexosamine content increases with weight more nearly in a proportional manner so that the ratio of hexosamine to collagen falls as the weight increases. Several pilot experiments were carried out to determine the effects of a variety of factors upon the production of hexosamine and collagen in skin.

Enhancement of experimental atherosclerosis by ACTH in the dog.

Summary One to 3 injections of 40 units of ACTH-gel significantly enhanced the elevated serum cholesterol and phospholipid levels produced by subsequent thiouracil and cholesterol feeding in the dog. This effect was associated with paralytic strokes in 4 of 10 dogs. Autopsy revealed markedly more widespread and more severe atherosclerosis in dogs pretreated with ACTH than in dogs who received only a high thiouracil and cholesterol diet. The authors are indebted to Drs. Wilfrid Dixon and Frederick Moore for statistical evaluation of the data and Drs. John Mehl and Ross Jacobs for supervision of lipid and lipoprotein determinations.

Effect of Adrenalectomy on Spontaneous and Induced Proteinuria in the Rat.

Summary 1. Bilateral adrenalectomy abolishes or greatly reduces the types of experimentally produced proteinuria studied in the saline maintained rat. 2. The normal, spontaneous proteinuria of the male rat is significantly reduced by bilateral adrenalectomy. 3. Cortisone administration to bilaterally adrenalectomized male rats increases their spontaneous proteinuria to normal control levels. 4. Adrenal cortex extract, esoxycorticosterone acetate, and cortisone restore the ability of the salt-maintained, adrenalectomized rat to respond to renin injection with massive proteinuria.

Collagen and hexosamine content of femurs of rats.

Summary The collagen and hexosamine contents of the femurs of growing rats were determined. Regression equations were derived upon the basis that there is a linear relationship between the logarithm of body weight and of femur length and the logarithm of the quantity of collagen and hexosamine. Rate of collagen deposition decreases somewhat as the animal grows. Rate of deposition of hexosamine-containing material, decreases markedly so that the ratio of hexosamine to collagen decreases with growth.

Effect of premarin on survival in men with myocardial infarction.

Conclusion The incidence of deaths due to arteriosclerotic heart disease is being compared in men recovered from myocardial infarction and treated 75 days or more with either Premarin or no estrogen (control), allocation of treatments being randomized. Survival rate in those receiving Premarin is significantly higher than in controls.

Abnormalities in urinary hormone patterns in lung cancer and emphysema

Urinary hormone excretion patterns were studied in 55 lung cancer patients, 45 sick controls with pulmonary emphysema and 59 well controls, all men. The patterns included estrone, estradiol, estriol, androsterone, etiocholanolone, 11‐oxygenated‐17‐ketosteroids, beta fraction, pregnanediol, Porter‐Silber chromogen, 17‐ketogenic steroids and the biological activity, protein content and carbohydrate content of the gonadotropin residue. Lung cancer patients were classified by cell type into adeno, squamous and anaplastic carcinoma. The mean urinary hormone pattern for each cancer cell type and for emphysema was compared with that for the well individuals. Analysis using linear discriminant function showed that each sick group had an abnormal and distinctive pattern as compared to the normals. The findings suggest that changes in the endocrine system are associated with the particular type of lung cancer present and to a lesser degree with emphysema. This is of particular interest in a disease of an organ usually considered to be independent of endocrine control.

The steroid feedback mechanism.

The mechanism whereby high blood levels of the adrenal cortical hormones inhibit the secretion of ACTH following stress has been investigated. The 4-hour change in circulating eosinophils was used as criterion for ACTH secretion. DCA administration into intact rats prevented the endogenous mobilization of ACTH following stress. When the venous brain blood from the stressed hypophysectomized rat was injected into these DCA-treated intact rats, a discharge of ACTH occurred in the recipients as indicated by a pronounced 4-hour eosinopenia. Carotid artery blood from stressed hypophysectomized rats was relatively inactive in provoking ACTH secretion when injected into intact DCA-treated recipients. If DCA is administered to the hypophysectomized donor rat, its brain blood contains no, or only slight, pituitary stimulating activity. It is concluded that at least one mechanism whereby high levels of the adrenal cortical hormones inhibit the release of ACTH following stress is by blocking the secretion from a cerebral structure, presumably the hypothalamus, of a pituitary stimulating substance (s).