Origin of serum estradiol in postmenopausal women.

In postmenopausal women, the circulating levels of estrone (E1) and estradiol (E2) may be of clinical importance. The origin of E1, but not of E2, has been defined. To examine the source of the latter, the serum concentrations, metabolic clearance rates, conversion ratios, and production rates of testosterone (T), androstenedione (A), E2, and E1 were measured in 20 postmenopausal subjects. For E2, the mean +/- SE CRTE2 was 0.0014 +/- 0.0005; thus, the contribution of circulating T to the circulating E2 pool was minimal (2.5%). The contribution of circulating A to E2 was also insignificant, whereas the CRE1E2 was appreciable (0.065 +/- 0.011), accounting for 21.5% of the E2 pool. For E1, the major contribution was the peripheral conversion of A, accounting for 24.6% of circulating E1. The contribution of peripheral conversion of T (unmeasurable) and E2 (2.9%) to the E1 pool were minimal. These data are consistent with the concept that in postmenopausal women the major contribution of peripheral conversion to the circulating E2 pool is from E1, which in turn is the product of peripheral aromatization of circulating A.

Ovarian and adrenal steroidogenesis in a virilized patient with gonadotropin-resistant ovaries and hilus cell hyperplasia.

A 26-year-old woman with secondary amenorrhea, temporal balding, and clitoromegaly was found to have both the gonadotropin-resistant ovary syndrome and hilus cell hyperplasia. Simultaneous sampling of peripheral and ovarian venous blood revealed excess ovarian testosterone secretion to be the probable cause of the patient's virilism. The marked response of the ovary to stimulation by luteinizing hormone (LH) coupled with the lack of ovarian follicular development suggested that an isolated resistance of the ovarian follicle to follicle-stimulating hormone (FSH) was present in this patient. The administration of a daily pharmacologic dose of dexamethasone for 14 days was followed by the patient's first menstrual period in 13 years, raising the possibility that autoimmunity may have been involved in this patient's ovarian resistance to FSH stimulation.

Serum androgens and estrogens in postmenopausal women with and without endometrial cancer.

Thirty-five consecutive patients with adenocarcinoma of the endometrium and an equal number of control subjects matched to the cancer patients for age and percentage of ideal weight were studied prospectively. In the cancer patients, the mean +/- SE serum androstenedione, testosterone, estrone (E1) and estradiol (E2) levels were 503 +/- 34 pg/ml, 224 +/- 22 pg/ml, 38.7 +/- 3.6 pg/ml, and 14.5 +/- 0.9 pg/ml, respectively. Similar concentrations were found in the control subjects. Body weight and percentage of ideal weight showed highly significant correlations (P less than 0.001) with E1 and E2 but not with the androgen concentrations in either group. The heavier patients had higher E1 and E2 levels. Age and years since menopause did not correlate with any of the hormonal levels. The cancer patients with overt diabetes tended to be more obese and have higher estrogen levels than did the nondiabetic subjects. Those with a history of prior estrogen usage were more slender and had lower endogenous estrogens than the nonusers. Twenty-three of the cancer patients (66%) had a presumed risk factor(s) for the development of this tumor, that is, excess body weight, high endogenous estrogen levels, or a history of prior estrogen usage. These data support the concept that conditions which lead to continued, unopposed estrogen stimulation may be associated with malignant transformation of the endometrium.

Age-related changes of calcitonin secretion in females.

Calcitonin secretion was studied in 50 normal females from 20--69 yr of age, with 10 subjects in each decade. Hormone measurements were made by RIA during response to a 10-min infusion of calcium (as the chloride salt) at 3 mg/kg BW. There was a progressive decrease of the calcium-stimulated plasma calcitonin with age. Linear regression analysis demonstrated a significant (P less than 0.05) negative correlation (r = 0.29) between calcitonin response and age. Postmenopausal females had a significantly (P less than 0.01) smaller calcitonin response than premenopausal females. The time of maximum calcitonin response progressively shifted from 10 min in the younger subjects to 20 min in the older subjects. These studies demonstrated that calcitonin secretion decreases with age in females. This decrease may play some role in the pathogenesis of the progressive loss of bone mass which occurs with aging in females.

Relationship of fasting urinary calcium to circulating estrogen and body weight in postmenopausal women.

Circulating estradiol (E2), estrone (E1), adrostenedione, and testosterone levels were measured in 40 normal postmenopausal women of widely varying body weights. The fasting urinary calcium to creatinine ratio (Ca:Cr) was also quantitated as an index of bone resorption. Significant positive correlations of E2 and E1 were found with body weight and correlations of E2 and E1 were found with body weight and percent ideal weight but not with height, age, or years since menopause. No correlations were observed between circulating androstenedione and testosterone levels and any of these characteristics. Significant negative correlations were noted between Ca:Cr and percent ideal weight and between Ca:Cr and E2 and E1 concentrations. Administration of 10 micrograms ethinyl E2 to 10 postmenopausal subjects for 30 days reduced Ca:Cr to the level observed in 20 premenopausal women. These data suggest that body weight can influence urinary calcium excretion. It is possible that the reduced amounts of endogenous estrogen found in conjunction with low body weight may be a factor contributing to the greater loss of urinary calcium and the more frequent occurrence of osteoporosis in slender postmenopausal women.

Elevations in skin temperature of the finger as an objective index of postmenopausal hot flashes: standardization of the technique.

The present study was designed to validate and standardize a technique of continuous recording of skin temperature of the finger as an objective index of hot flashes. Significant skin temperature rises (greater than 1 degree C) were recorded in close temporal relationship to 69% of subjective hot flashes experienced by seven postmenopausal women. The temperature elevations occurred at an interval of 54 +/- 10 minutes (mean +/- standard error) and lasted an average of 31 minutes. The mean increase was 2.7 degrees +/- 0.2 degrees C. The extent of the temperature elevations found in the postmenopausal subjects was significantly greater than in premenopausal control subjects (P less than 0.05) and was reduced by estrogen treatment (P less than 0.02). This study substantiates that the recording of skin temperature changes of the finger provides an objective index of hot flashes. This should assist in the investigation of the underlying disturbance and provide more accurate evaluation of modes of therapy.

Inhibition of peripheral aromatization of androstenedione to estrone in postmenopausal women with breast cancer using delta 1-testololactone.

To determine if delta 1-testololactone can inhibit the peripheral aromatization of androstenedione (delta), nine postmenopausal women with metastatic breast cancer were studied before and after 2 weeks of therapy with 250 mg of the drug, given every 6 h by mouth. The conversion ratio of delta to estrone (E1) was significantly reduced (P less than 0.005) from a mean (+/-SE) of 0.0098 +/- 0.0025 before to 0.0009 +/- 0.0005 after treatment. The drug's effect on the metabolism of delta seemed to be specific since significant changes in the MCR of delta and in the conversion ratio to testosterone were not observed. That this inhibition of peripheral aromatization had an effect on E1 metabolism was shown by the significant decrease (P less than 0.01) of mean serum E1 levels from 22 +/- 3 pg/ml before to 12 +/- 1 pg/ml after treatment. Serum estradiol levels rose slightly from 8 +/- 0.8 to 12 +/- 4 pg/ml. Serum delta and testosterone levels were unchanged by therapy. These data are consistent with the concept that delta 1-testololactone is a potent inhibitor of peripheral aromatization of delta to E1. This mechanism could explain the antitumor properties of this compound.