S.M. Slayden

Hyperandrogenemia in patients presenting with acne

OBJECTIVE To determine whether acne is associated with hyperandrogenemia, regardless of age of presentation. DESIGN Prospective controlled study. SETTING Tertiary-care medical center. PATIENT(S) Thirty consecutive unselected women presenting with acne and no hirsutism and 24 eumenorrheic healthy controls. INTERVENTION(S) Serum samples was taken in all patients, and an acute 60-minute ACTH-(1-24) test was performed in 19 patients. MAIN OUTCOME MEASURE(S) Total and free T, sex hormone-binding globulin (SHBG), and DHEAS levels in basal samples, and ACTH-stimulated 17-hydroxyprogesterone (17-HP) response to exclude 21-hydroxylase (21-OH)-deficient nonclassic adrenal hyperplasia (NCAH) were determined. RESULT(S) Nonhirsute patients with acne demonstrated significantly lower levels of SHBG and higher free-T and DHEAS levels than controls. Nineteen (63%) acneic patients had at least one androgen value above the 95% of controls. In patients aged 12-18 years, 7/8 (88%) had at least one increased androgen value, compared with 12/22 (55%) patients aged 19-43 years. One patient (5.3%) was found to have 21-OH-deficient NCAH. CONCLUSION(S) Hyperandrogenemia was evident in a majority of nonhirsute acneic patients studied, regardless of age. These data suggest that androgen suppression may be useful in treating acne in many of these patients.

The 21-Hydroxylase-Deficient Adrenal Hyperplasias: More Than ACTH Oversecretion

Twenty-one hydroxylase (21-OH)-deficient classic adrenal hyperplasia (CAH) and nonclassic adrenal hyperplasia (NCAH) are two of the most common genetic disorders known to man, yet the machanism(s) resulting in steroid excess remains unclear. Overactivation of the hypothalamic-pituitary-adrenal (HPA) axis and increased ACTH secretion appear to be important mechanisms resulting in steroid excess in untreated patients, at least in the classic forms of the disorder. Nonetheless, most NCAH patients do not demonstrate overactivity of the HPA axis. A few of these patients may demonstrate a mild degree of ACTH hyper-responsiveness to corticotropin-releasing hormone stimulation, and up to 40% have radiologic evidence of adrenocortical hyperplasia and/or isolated adenomas, suggesting that some degree of chronic ACTH excess is present. Another mechanism resulting in adrenocortical excess in adrenal hyperplasia, and primarily in NCAH, follows the alteration in enzyme kinetics resulting from the mutation of 21-OH. The mutated enzyme product is less efficient than the wild type, resulting in an increased precursor to product ratio, independent of ACTH levels. Hence, progesterone (P4) and 17-hydroxyprogesterone (17-HP) levels in these patients may remain above normal even in the presence of excess glucoroticoid administration. Overactivity of the renin-angiotensin system may also be important in stimulating adrenocortical steroidogenesis in patients with salt-wasting and in some with simple virilizing CAH. Alterations in ovarian and gonadotropic function, with the appearance of a polycystic ovary-like picture, also contribute to the androgen excess of these patients. Functional ovarian abnormalities in patients with CAH or NCAH may relate to a number of causes, including prenatal masculinization of the hypothalamic-pituitary-ovarian (HPO) axis by adrenal androgens, continued disruption of the HPO axis by persistently elevated P4 or androgen levels, and/or a direct glucocorticoid effect. Finally, these data suggest that the measurement of P4 or 17-HP may not be the most accurate marker of therapeutic efficacy, and suppression of both the ovaries and adrenals may be necessary for optimum steroidogenic control.

Fertilization Potential of Human Sperm Is Correlated with Endogenous Platelet-Activating Factor Content

AbstractPurpose: Platelet-activating factor (PAF) is a potent signaling phospholipid that is found in mammalian sperm and has a positive correlation with fertility. Whereas PAF is present in human sperm, there are no relational reports on its content and the cells fertilization potential. Therefore, the study objective was to determine if PAF content in capacitated-induced sperm is related to fertilization potential as determined by the sperm penetration assay (SPA). Methods: Endogenous sperm lipids were measured for PAF content by a specific radioimmunoassay following insemination of zona pellucida-free hamster ova. Data were analyzed by regression analysis and Students t test. Results: Regression analysis revealed a positive and significant relation (R2 = 0.806; P < 0.05) between PAF content in human sperm and SPA outcome (pass: ≥5.0; fail: <5.0, penetrations/ova). Patients that passed (22.61 ± 5.21 picomoles/106) the SPA had significantly (P < 0.01) higher PAF levels in their sperm than patients that failed (12.91 ± 1.76 picomoles/106 cells) the test. Conclusions: PAF content in capacitated-induced sperm has a significant and positive relationship with fertilization potential. Fertilization potential may be predicted by measuring PAF levels in capacitation-induced human sperm. Determining PAF content in capacitated human sperm may be a beneficial diagnostic tool for the infertility specialist.