Richard N. Andersen

Changes in plasma hormones across the menstrual cycle in patients with menstrually related mood disorder and in control subjects

A variety of hypotheses have been proposed to explain the premenstrual syndromes. These hypotheses serve as rationales for an equally diverse range of proposed treatments. To investigate these hypotheses, we obtained multiple blood samples across the menstrual cycle in women with well-characterized menstrually related mood disorder and in control subjects. No diagnosis-related differences were observed in the levels or patterns of secretion of progesterone, estradiol, follicle-stimulating hormone, luteinizing hormone, testosterone-estradiol-binding globulin, dehydroepiandrosterone sulfate, dihydrotestosterone, prolactin, or cortisol. Our data suggest that premenstrual syndrome does not represent a simple hormonal deficiency and that the cited rationales for several of the proposed treatments are of questionable merit.

Oral dehydroepiandrosterone in physiologic doses modulates immune function in postmenopausal women

OBJECTIVE This study tests the hypothesis that dehydroepiandrosterone or its metabolic products are immunomodulatory in postmenopausal women with relative adrenal androgen deficiency. STUDY DESIGN A prospective, randomized, double-blind, crossover study of 11 subjects with 3-week treatment arms separated by a 2-week washout period was performed. Immunologic evaluation at the beginning and end of the treatment arms consisted of flow cytometry to delineate T-cell populations, in vitro T-cell mitogenic response and cytokine production, and natural killer cell cytotoxicity. Statistical analysis was based on a split-plot design with analysis of variance with repeated measures. RESULTS Dehydroepiandrosterone supplementation decreased CD4+ (helper) T cells and increased CD8+/CD56+ (natural killer) cells. Although T-cell mitogenic and interleukin-6 responses were inhibited, natural killer cell cytotoxicity increased dramatically. CONCLUSIONS These data provide the first in vivo evidence in human for an immunomodulatory effect of dehydroepiandrosterone. The salutary immune changes could account for clinical and experimental evidence of antioncogenic effects of this steroid. This study provides a strong rationale for further clinical studies on dehydroepiandrosterone supplementation in adrenal androgen-deficient states.

Sedative and hypnotic effects of oral administration of micronized progesterone may be mediated through its metabolites

Progesterone and its metabolites were measured in serum extracts by radioimmunoassay and gas chromatography-mass spectrometry, respectively, after ingestion of micronized progesterone by eight postmenopausal women. One subject received 400 mg of micronized progesterone orally that induced a hypnotic state that lasted for approximately 2 hours. Blood samples were drawn periodically from all subjects for measurement of progesterone and its metabolites in serum. Levels of serum progesterone and its metabolites increased significantly from baseline values and reached a peak between 2 and 6 hours after oral progesterone administration. Significant quantities of five compounds (progesterone, 5 alpha-pregnan-3 alpha-ol-20-one, 5 beta-pregnan-3 alpha-ol-20-one, 5 beta-pregnan-3 alpha,20 beta-diol, and 5 beta-pregnan-3 alpha-ol-11,20-dione) that have been reported to possess anesthetic qualities were identified. The sedative and hypnotic effects of oral administration of progesterone may be mediated through those compounds.

Androgen parameters and their correlation with body weight in one hundred thirty-eight women thought to have hyperandrogenism

The first objective of this study was to determine which plasma androgen assay or combination of assays would be the most useful in documenting hyperandrogenism in women with hirsutism, acne, oligomenorrhea, or unexplained infertility. Plasma levels of androstenedione (A), total testosterone (T), and dehydroepiandrosterone sulfate (DHEAS) were measured and free T (FTc) was calculated from the measured total T and T-estradiol-binding globulin binding capacity (TeBG-BC) in 138 consecutive women referred to our clinic for hirsutism, acne, oligomenorrhea, and/or unexplained infertility. FTc was elevated in 82% and was most frequently elevated parameter. DHEAS was elevated in 59% of the women, and 93% were noted to have hyperandrogenemia on the basis of a combination of FTc and DHEAS levels. The second objective of this study was to determine whether there was significant correlation between the androgen parameters and any of the clinical features. Body weight was significantly negatively correlated with DHEAS and TeBG-BC in those women with a normal DHEAS level but not in those with an elevated level. A strong positive correlation (simple and partial) was noted between body weight and plasma T levels in the whole group of patients, as well as in those with a normal or an elevated DHEAS level. It is suggested that the relationship between T and body weight is multifaceted. Conceivably, T could influence body mass by effects on food intake or through alterations in intermediary metabolism.

The effectiveness of two oral contraceptives in suppressing plasma androstenedione, testosterone, LH, and FSH, and in stimulating plasma testosterone-binding capacity in hirsute women

The effectiveness of two oral contraceptives in suppressing plasma androstenedione (A), testosterone (T), LH, and FSH and in stimulating testosterone-estradiol-binding globulin (TeBG) was evaluated in 39 hirsute women. Twenty-seven hirsute women received norethindrone 2 mg.-mestranol 0.1 mg. (Group I) and 12 received norgestrel 0.5 mg.-ethinyl estradiol 0.05 mg. (Group II). Hormone assays were performed before treatment and at the end of 3 weeks of therapy. Ninety percent of the women in both groups had an elevated plasma A and/or T. During treatment, plasma A,T, LH, and FSH were significantly reduced in both groups (p less than 0.01). In Group I, 78% of the women had a normal plasma A and T during treatment. In Group II, 83% of the women had a normal A and T during treatment. There was a greater increase in TeBG in Group I (p less than 0.01). It is concluded that these two oral contraceptives effectively suppressed the hyperandrogenism of most of the hirsute women.

Replacement of dehydroepiandrosterone enhances T-lymphocyte insulin binding in postmenopausal women * †

OBJECTIVE To demonstrate bioavailability of 3 weeks of oral micronized DHEA and to delineate changes induced on insulin sensitivity, morphometric indexes, and lipoprotein profiles. DESIGN Oral micronized DHEa (50 mg/d) was administered in 3-week treatments to 11 postmenopausal women in a prospective, placebo-controlled, randomized, blinded, crossover trial with an interarm washout. After dose (23 hour) serum DHEA, DHEAS, T, and cortisol levels were measured, as were fasting lipoproteins, oral glucose tolerance tests (OGTT), T-lymphocyte insulin binding and degradation, and urine collagen cross-links. Morphometric changes were determined by hydrostatic weighing. RESULTS Dehydroepiandrosterone sulfate, DHEA, T, and free T increased up to two times premenopausal levels with treatment. Fasting triglycerides declined; no change in collagen cross-links or morphometric indexes was noted. Oral glucose tolerance test parameters did not change, but both T-lymphocyte insulin binding and degradation increased with DHEA. CONCLUSION Fifty milligrams per day of oral DHEA gives suprahysiologic androgen levels; 25 mg/d may be more appropriate. Dehydroepiandrosterone enhanced tissue insulin sensitivity and lowered serum triglycerides. Rationale is provided for postmenopausal replacement therapy with this androgen.

Familial Male Pseudohermaphroditism without Gynecomastia Due to Deficient Testicular 17-Ketosteroid Reductase Activity

Abstract To evaluate possible 17-ketosteroid reductase deficiency, we studied two sisters with primary amenorrhea, hirsutism, clitoral enlargement and a 46,XY karyotype, who lacked breast development. Plasma luteinizing hormone, follicle-stimulating hormone and urinary 17-ketosteroids were elevated in both subjects. Plasma Δ4-androstenedione was seven to nine times greater than normal, whereas plasma testosterone was low or in the low-normal male range. Spermatic venous plasma of Case 2 contained increased amounts of Δ4-androstenedione and estrone and subnormal amounts of testosterone and estradiol, findings consistent with testicular 17-ketosteroid reductase deficiency. In vitro incubation of testicular tissue of Case 2 confirmed a partial defect in testicular 17-ketosteroid reductase activity and documented increased 3β-hydroxysteroid dehydrogenase activity. Failure of breast development was probably due to lower estrogen levels than in previously reported cases. We conclude that testicular 17-ketostero...

Identification of fatty acid amides in human plasma

A family of five long-chain fatty acid carboxamides has been identified and semi-quantified in human plasma by GC-MS. One saturated and four unsaturated amides were found. Luteal phase plasma from 16 women was studied, and all five of the amides were found in ten of the subjects, but none in the other six. The structure of these endogenous amides was established by comparing their GC and MS characteristics with those of the synthetic amides prepared by ammonolysis of corresponding long-chain fatty acid acyl chlorides.

Familial ovarian hyperthecosis: A study of two families☆☆☆

Abstract Two families containing 41 women with hirsutism and/or oligomenorrhea were studied. Ovarian histology of eight demonstrated hyperplasia of theca cells in atretic follicles, a paucity of primordial and developing follicles, and stromal hyperplasia. Elevated levels of androstenedione and/or testosterone and luteinizing hormone (LH) were found. Estradiol and follicle-stimulating hormone (FSH) were low. Following bilateral ovarian wedge resection, the LH and FSH levels of the proband of Family I were normal. Three men of Family I had low plasma testosterone and an abnormally high LH/FSH ratio similar to that of the women. Conclusions were: (1) Ovarian hyperthecosis can be inherited; (2) the inheritance is consistent with an autosomal dominant pattern, but X-linked inheritance cannot be ruled out if the males are excluded; (3) the abnormal LH/FSH ratio can serve as a biochemical marker; (4) ovarian wedge resection corrected the abnormal LH/FSH ratio in one case; and (5) ovarian hyperthecosis may be a type of gonadal dysgenesis.

Fetus-placenta-newborn

Abstract OBJECTIVE: Our purpose was to determine whether third-trimester maternal serum α-fetoprotein predicts adverse perinatal outcome and whether use of both second- and third-trimester maternal serum α-fetoprotein enhances the positive predictive value for various abnormal outcomes. STUDY DESIGN: A cohort study with obstetric outcome assessed by chart analysis after delivery was performed at Regional Medical Center (Memphis, Tennessee), a hospital staffed by university-based physicians saving a large urban population with many indigent patients. A total of 650 women attending prenatal clincis in the above setting with a singleton pregnancy without a neural tube defect, contributing a maternal blood samples in both the second and third trimesters, and delivered in the above hospital participated. Various pregnancy outcomes were correlated with maternal serum α-fetoprotein levels in the second the third trimesters and in both. RESULTS: In the third trimester no significant associations were found between maternal serum α-fetoprotein elevations and pregnancy complications. In the second trimester elevation (≥2.0 multiples of the median) were, by contrast, significantly associated with preterm premature rupture of the membranes, preterm birth, and low birth weight. No association was found with certain other complications. When second-trimester data were grouped according to the types of complications occurring in individual women, only preterm premature rupture of the membrane proved statistically significant. CONCLUSIONS: Second-trimester but not third-trimester maternal serum α-fetoprotein is significantly elevated with preterm premature rupture of the membranes, preterm birth, and low birth weight; in this conhort study no association was found with preeclampsia, oligohydramnios, or polyhydramnios.