Adverse effects of spironolactone therapy in women with acne.
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Biomedical subjects
Publications and source records attributed to L I Rose.
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BACKGROUND: Androgen excess is frequently associated with oligomenorrhea as well as acne. Oligomenorrhea in hirsute women has been demonstrated to be associated with higher active testosterone levels than found in eumenorrheic hirsute women. This study was designed to evaluate whether similar findings are present in women with acne. Forty-four consecutive women with acne were evaluated by measuring their levels of total testosterone, biologically active testosterone, and free testosterone. The women with oligomenorrhea and acne had significantly higher levels of biologically active testosterone than those with eumenorrhea and acne. This implies that biological active testosterone should be measured in oligomenorrheic women with acne and, if elevated, consideration should be given to antiandrogen therapy. METHODS: Data were collected from 44 consecutive Caucasian women aged 14 to 38 years. The patients were separated into two groups based on menstrual history. Group 1 had regular menses, and group 2 had oligomenorrhea, defined as menstrual intervals of greater than 36 days. All patients had blood samples drawn on their initial office visit, regardless of the phase of the menstrual cycle, and the levels of total testosterone (TT), biologically active testosterone (BT), and free testosterone (FT) were obtained. RESULTS: The serum TT level was 87 +/- 41.3 ng/dL (range, 31-150 ng/dL) in oligomenorrheic women and 56 +/- 27.5 ng/dL (range 8-107 ng/dL) in eumenorrheic women. There was no statistically significant difference. The serum BT level in oligomenorrheic women was 33 +/- 16.9 ng/dL (range, 11-51 ng/dL) and in eumenorrheic women 19 +/- 13.6 ng/dL (range, 11-51 ng/dL). This difference was statistically significant (p < 0.05). The serum FT level in oligomenorrheic women was 18 +/- 9.4 pg/mL (range, 1-29 pg/mL) and in eumenorrheic women 10 +/- 7.1 pg/mL (range, 1-32 pg/mL). This difference was not statistically significant (Table 1). CONCLUSIONS: Women with acne and oligomenorrhea, similar to women with hirsutism and oligomenorrhea, have higher levels of biologically active testosterone than those with normal menses.
This is the case of a large 2 x 1.5 cm adrenal tumor demonstrated on CT scan that was proven biochemically and surgically to be an aldosteronoma and that did not concentrate 6-beta(131I)-iodo-methyl-19-norcholesterol (NP-59). Before the publication of this case, all CT-identified aldosteronomas of greater than 1 cm have concentrated NP-59. Previously, an adrenal mass of greater than 1 cm that failed to concentrate NP-59 was excluded from being an aldosteronoma. This concept must be reevaluated with the publication of this case.
The patient with type II, or non-insulin-dependent, diabetes mellitus (NIDDM) is characterized by obesity and insulin resistance, with resultant hyperinsulinemia and hyperglycemia. Sulfonylureas are the chief therapy for patients with NIDDM; for a limited time, these agents stimulate increased insulin secretion. With chronic administration, sulfonylureas improve the diabetic patient's insulin activity by increasing cellular insulin receptors and reducing insulin postreceptor defects. Metformin, a drug in the biguanide class, is now approved for use in the United States. This drug does not stimulate insulin release but works by lowering glucose in peripheral tissues. It can be used alone or in combination with a sulfonylurea. With sulfonylureas and metformin, therapy for the patient with NIDDM can be more effectively tailored.
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BACKGROUND: To evaluate the possible benefits of the addition of intermediate-acting insulin administered at bedtime to therapy with daytime sulfonylureas in patients with non-insulin-dependent diabetes mellitus for whom maximal doses of oral hypoglycemic agents have not been successful. METHODS: Study subjects were 16 consecutive obese patients aged from 44 to 78 years (mean age, 62 years) with histories of non-insulin-dependent diabetes mellitus for a mean of 9 years. None of the subjects had been able to control their diabetes with maximal doses of oral hypoglycemic agents. All patients received 20 mg glipizide or 10 mg glyburide twice a day, as well as education about the American Diabetes Association diet. Neutral protamine Hagedorn (NPH) insulin was empirically added in doses from 0.1 to 0.2 units/kg given at bedtime. The dose was adjusted on the basis of fasting blood glucose levels. RESULTS: Mean fasting blood glucose decreased from 13.7 +/- 3.4 to 8.3 +/- 2.7 mmol/L at 3 months and 7.3 + 2.0 mmol/L at 1 year. Glycosylated hemoglobin decreased from 9.0% +/- 1.9% to 6.2% +2- 1.16% at 3 months and 6.3% +/- 1.22% at 1 year. CONCLUSION: A late-night dose of NPH insulin was added to a regimen of daytime sulfonylureas in a group of obese patients with type II diabetes whose hyperglycemia was not controlled with maximal doses of oral hypoglycemic agents. This treatment proved to be beneficial and is a useful alternative to conventional insulin therapy in this group of patients.
Twenty consecutive women referred for evaluation and treatment of idiopathic hirsutism were evaluated with regard to levels of serum androgens, degree of hirsutism, nature and prevalence of psychological symptoms, and mood and affects. Androgens measured were total testosterone, free testosterone, biologically active testosterone, dehydroepiandrosterone, dehydroepiandrosterone sulfate and androstenedione. Psychological symptoms were quantified via the Derogatis Symptom Inventory, and mood and affects were measured by the Affects Balance Scale. Results revealed very significant correlations between unbound fractions of testosterone (i.e. free and biologically active testosterone) and both symptom and mood measures of depression (r = 0.60; p < 0.01). Significant inverse correlations were also observed between unbound fractions of testosterone and positive affects measures (e.g. 'contentment' r = -0.51; p < 0.05). Correlations between total testosterone and psychological variables were non-significant in all instances. Measures of degree of hirsutism correlated approximately zero (o) with psychological symptom and mood measures in this sample. When psychiatric 'caseness' criteria were applied to the cohort, seven of the 20 women (35%) were found to be positive. Results are interpreted to suggest that depression among hirsute women appears more likely to have its basis in a deranged neuroendocrine mechanism than in psychosocial causes.
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BACKGROUND: Measurement of serum 5 alpha-androstane-3 alpha, 17 beta-diol glucuronide (3 alpha-diolG) has been proposed as a useful biochemical marker of peripheral androgen metabolism. Is 3 alpha-diol G a useful biochemical marker of peripheral androgen metabolism and does it correlate with degree of facial hirsutism? OBJECTIVE: Our purpose was to assess possible correlation between serum 3 alpha-diol G and degree of facial hirsutism and to compare serum 3 alpha-diol G levels with levels of other commonly measured serum androgens. METHODS: Twenty-three consecutive women with facial hirsutism were studied, and serum concentrations of 3 alpha-diol G, testosterone (total, free, and biologically active portions), dehydroepiandrosterone sulfate, and androstenedione were measured. RESULTS: There was no correlation between serum 3 alpha-diol G levels and degree of facial hirsutism. There was a correlation between levels of 3 alpha-diol G and dehydroepiandrosterone sulfate (p less than 0.01), biologically active testosterone (p = 0.01), free free testosterone (p less than 0.02), and androstenedione (p less than 0.05). CONCLUSION: Serum 3 alpha-diol G concentrations have no correlation with degree of facial hirsutism and do not provide additional information over the commonly measured androgens.
BACKGROUND: Studies on the psychopathologic aspects of hirsutism are sparse. Attempts to correlate these aspects with either the extent of the facial hirsutism and/or circulating serum androgens are virtually nonexistent. This study evaluates the psychopathologic aspects of hirsutism and correlates these findings with the extent of the facial hirsutism as well as with the circulating serum androgens. OBJECTIVE: Our purpose was to assess the psychopathologic aspects of facial hirsutism and to determine whether any correlation exists between these findings and either the extent of the facial hirsutism or the circulating serum androgens. METHODS: Twenty consecutive women with facial hirsutism were studied by administration of psychologic tests (DeRogatis Symptom Inventory and the Affects Balance Scale). The results of these tests were correlated with the grade of facial hirsutism as well as serum levels of total testosterone (T), biologically active testosterone (BT), free testosterone (FT), dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEA-S), and androstenedione (A-dione). RESULTS: Significant levels of depression were found. No correlation was found between the psychopathologic measurements and the extent of facial hirsutism or serum levels of T, DHEA, DHEA-S, and A-dione. Significant correlations were found between depression and serum levels of FT and BT. CONCLUSION: There is an increased incidence of depression in facially hirsute women and this correlates with their circulating active testosterone levels and not with the extent of their facial hirsutism.
The pathogenesis of benign prostatic hyperplasia is related to the action of 5 alpha-dihydrotestosterone (DHT), the physiologically active form of testosterone. The conversion of testosterone to DHT is catalyzed intracellularly in prostatic tissue by the enzyme 5 alpha-reductase. Finasteride blocks the action of 5 alpha-reductase by competitively inhibiting the binding of testosterone to 5 alpha-reductase. The maximum effect of finasteride on reducing prostatic volume occurs after three months of oral therapy. Most patients experience improvement in urine flow rates, and side effects are minimal. However, following discontinuation of treatment, serum DHT levels return to baseline within two weeks.
Antiandrogens have been found to be effective in the treatment of acne and hirsutism. Cyproterone acetate has been used in Europe for many years, but in the United States it has only been approved as an orphan drug to treat severe hirsutism. Spironolactone is approved in the United States for its antialdosterone effect but not for its antiandrogenic effect, although it is widely used for the latter purpose. While cyproterone is a more effective drug than spironolactone, it is more likely to produce undesirable side effects.
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A recent study demonstrated that hirsute women with irregular menses had higher levels of serum androgens that hirsute women with regular menses. To investigate this finding, we measured total testosterone, biologically active testosterone, free testosterone, androstenedione, dehydroepiandrosterone, and dehydroepiandrosterone sulfate in 51 hirsute women with regular menses and compared the levels found to those found in 28 hirsute women with oligomenorrhea. There was no significant difference in the degree of facial hirsutism between the two groups. Oligomenorrheic women had significantly higher levels of free testosterone (p less than 0.02) and biologically active testosterone (p less than 0.05). The other androgens did not differ significantly between the two groups. The free fractions of testosterone are the metabolically active forms of the hormone and their levels are a function of the rates of production and clearance of testosterone that are elevated in states of hyperandrogenism. This study confirms that hirsute women with oligomenorrhea have higher levels of free and biologically active testosterone than those with regular menses.
Gonadotropin-releasing hormone (GnRH), a decapeptide synthesized and released by the hypothalamus, regulates production and release of the gonadotropins luteinizing hormone (LH) and follicle-stimulating hormone (FSH) by the adenohypophysis. Parenterally administered GnRH was initially used diagnostically as a test of adenohypophyseal reserve of LH and FSH. Subsequently, native GnRH was used therapeutically to treat hypothalamic hypogonadal and infertility states in both men and women. Because of the low potency and short half-life of native GnRH, long-acting, potent analogs have been developed that suppress secretion of native pituitary gonadotropins, resulting in medical gonadectomy. When administered parenterally and, more recently, intranasally, these compounds are useful in the management of prostate and breast carcinoma, endometriosis and uterine leiomyomata, precocious puberty and nontumorous ovarian hyperandrogenic syndromes.
The cutaneous expression of Marfan's syndrome is generally limited to striae distensae and a number of uncommon associations with other dermatologic disorders. To date, there have been no reported cases of hair or nail abnormalities accompanying this disorder. We describe a patient with Marfan's syndrome who presented with an acquired white forelock and we review the literature on the association of poliosis with various entities.
The biphosphonates are becoming well established as effective agents for the treatment of metabolic bone diseases. Etidronate disodium is the only biphosphonate approved by the U.S. Food and Drug Administration. Accepted indications for etidronate therapy are symptomatic Paget's disease, heterotopic ossification and hypercalcemia of malignancy. An unapproved, but apparently successful use is treatment of postmenopausal osteoporosis. Both oral and intravenous preparations are available. Newer biphosphonates, which may be more efficacious and less toxic than etidronate, are being studied.
Many physicians routinely measure the gonadotropins PRL, LH, and FSH and the androgens dehydroepiandrosterone (DHEA), androstenedione (ADIONE), and testosterone, as well as testosterone's biologically active fractions in the evaluation of hirsute women. Is this cost effective? To answer this question, 38 consecutive premenopausal hirsute women were evaluated. Two women each had minor elevations in PRL and FSH, and 11 had minor elevations in LH. Three women had minor elevations in the LH/FSH ratio, and only one was above a ratio of 3, believed to be indicative of polycystic ovarian syndrome. Because these gonadotropin elevations did not correlate with the androgens measured and were of no value in the diagnosis or management of these women, they were not believed to be cost effective. Their routine measurements should be abandoned.