Shahla Nader

Acne and hyperandrogenism

Elevated serum androgen levels have been reported in patients with acne resistant to conventional dermatologic therapy. This study was designed to investigate the relationship between serum androgen levels and the presence of acne in an unselected population of women seen consecutively by a dermatologist for various dermatologic complaints. Elevated serum testosterone levels were associated with acne regardless of whether this was the presenting complaint or an incidental finding. Women with both acne and hirsutism had higher serum testosterone levels than those with acne alone. Higher incidence of irregular menstrual cycles was noted in women complaining of acne. Normal serum testosterone levels were found only in those patients with regular menstrual cycles and the absence of acne or hirsutism. In conclusion, this study suggests that elevated serum testosterone levels are related to the presence of acne. Attention is called to the possibility that acne may be a clinical manifestation of a disorder with systemic and reproductive consequences.

GnRH-Deficient Phenotypes in Humans and Mice with Heterozygous Variants in KISS1/Kiss1

CONTEXT KISS1 is a candidate gene for GnRH deficiency. OBJECTIVE Our objective was to identify deleterious mutations in KISS1. PATIENTS AND METHODS DNA sequencing and assessment of the effects of rare sequence variants (RSV) were conducted in 1025 probands with GnRH-deficient conditions. RESULTS Fifteen probands harbored 10 heterozygous RSV in KISS1 seen in less than 1% of control subjects. Of the variants that reside within the mature kisspeptin peptide, p.F117L (but not p.S77I, p.Q82K, p.H90D, or p.P110T) reduces inositol phosphate generation. Of the variants that lie within the coding region but outside the mature peptide, p.G35S and p.C53R (but not p.A129V) are predicted in silico to be deleterious. Of the variants that lie outside the coding region, one (g.1-3659C→T) impairs transcription in vitro, and another (c.1-7C→T) lies within the consensus Kozak sequence. Of five probands tested, four had abnormal baseline LH pulse patterns. In mice, testosterone decreases with heterozygous loss of Kiss1 and Kiss1r alleles (wild-type, 274 ± 99, to double heterozygotes, 69 ± 16 ng/dl; r(2) = 0.13; P = 0.03). Kiss1/Kiss1r double-heterozygote males have shorter anogenital distances (13.0 ± 0.2 vs. 15.6 ± 0.2 mm at P34, P < 0.001), females have longer estrous cycles (7.4 ± 0.2 vs. 5.6 ± 0.2 d, P < 0.01), and mating pairs have decreased litter frequency (0.59 ± 0.09 vs. 0.71 ± 0.06 litters/month, P < 0.04) and size (3.5 ± 0.2 vs. 5.4 ± 0.3 pups/litter, P < 0.001) compared with wild-type mice. CONCLUSIONS Deleterious, heterozygous RSV in KISS1 exist at a low frequency in GnRH-deficient patients as well as in the general population in presumably normal individuals. As in Kiss1(+/-)/Kiss1r(+/-) mice, heterozygous KISS1 variants in humans may work with other genetic and/or environmental factors to cause abnormal reproductive function.

Ageing and hormones

With ageing, there is a decline in hormone levels, including oestrogen, testosterone, dehydroepiandrosterone and growth hormone. Replacement of these hormones has been investigated and reviewed in this paper. There are still controversies regarding the benefits and risks of replacement therapy.

Acne and hyperandrogenism: Impact of lowering androgen levels with glucocorticoid treatment

The impact of lowering androgen levels with glucocorticoid treatment in a group of consecutive female patients presenting to the Department of Reproductive Medicine and Biology, University of Texas, with a chief complaint of acne has been studied. One hundred fifty-eight patients, ages 16 to 40, who received prednisone at a maximum daily dose ranging from 7.5 to 15 mg for a period of at least 6 months were selected for the study. These patients were not taking other systemic medication affecting androgens or acne. Only thirty patients (19%) had pretreatment testosterone levels below the upper limits (40 ng/dl) of our normal range; while on treatment 146 patients (92.4%) had testosterone levels below 40 ng/dl. In sixty-three patients (39.9%) the acne completely cleared, in eighty patients (50.6%) it significantly improved, and in only fifteen patients (9.5%) was the acne not affected by the medication. There was a highly significant difference between the mean testosterone levels during treatment of those who cleared or improved, versus those who did not (p less than 0.05), the percentage drop in testosterone being greatest in those who cleared. Pretreatment testosterone levels were not significantly different in those who cleared, improved or did neither. It is concluded that glucocorticoid treatment frequently results in a lowering of androgen levels in hyperandrogenic women with acne and that this is associated with clearing or improvement of the acne.

Endocrine profiles of patients with testicular tumors treated with radiotherapy

Blood samples for hormone analysis were obtained 5 to 20 years post-therapy from 12 men with testicular tumors who were originally treated by unilateral orchiectomy followed by abdominal and/or pelvic irradiation. In nine patients (75%) the levels of FSH and LH, and in one patient (8%) the testosterone values, were outside the ranges found in age- and sex-matched controls. From this retrospective study we conclude that, even when the remaining testis is kept outside the field of radiation, significant radiation damage occurs, mainly through scatter. This damage is more likely to occur if the hemiscrotum is irradiated. Methods of shielding are available to reduce the dose received by the contralateral testis.

Euthyroid sick syndrome in psychiatric inpatients

Numerous disorders are associated with euthyroid sick syndrome (ESS). This retrospective study examines the incidence and circumstances of ESS among 3188 psychiatric inpatients. There were 324 patients (10.2%) who met strictly defined criteria for ESS. Of these, 95 were hyperthyroxinemic (HT), 6 were hypothyroxinemic, 179 had mildly elevated thyroid-stimulating hormone (HTSH), and 47 had suppressed TSH. All were classified by DSM-III-R discharge diagnoses, encompassing five categories. chi 2 tests of significance of the 95 HT and 179 HTSH subjects revealed the following: 1) no relationship with age or gender; 2) the frequencies of HT and HTSH differed significantly (p < .05 and p < .01, respectively) across the five psychiatric categories; 3) HT frequency was highest in mood disorders (HT in mood versus others p < .02); and 4) HTSH frequency was highest in substance abuse (HTSH in substance abuse versus others p < .02). In conclusion, ESS is common in psychiatric inpatients, especially HT and HTSH; pathophysiologic mechanisms may vary according to psychiatric diagnosis.

Polycystic ovary syndrome and the androgen-insulin connection.

The association of hyperandrogenism, insulin resistance, and polycystic ovarian disease is well established. The accompanying hyperinsulinemia results in acanthosis nigricans, an epiphenomenon of this syndrome. The knowledge that states of insulin resistance of diverse causes are associated with ovarian hyperandrogenism makes the argument for insulin-driven ovarian androgen secretion compelling. However, equally compelling evidence suggests that hyperandrogenism may contribute to insulin resistance and hyperinsulinemia. The irreconcilable differences between these two hypotheses have resulted in an array of contradictory studies. In this article a unified concept of polycystic ovary syndrome and its androgen-insulin connection is proposed. The hypothesis incorporates the role of hyperinsulinemia in the androgen excess observed (and vice versa); the key to this connection is the androgen-dependent change in regional body fat distribution and its metabolic consequence. The pathophysiologic features of polycystic ovary syndrome, which has important clinical sequelae, deserve further consideration.

Luteal-phase support in stimulated cycles in an in vitro fertilization/embryo transfer program: Progesterone versus human chorionic gonadotropin

A study was undertaken to compare the hormonal parameters [serum concentrations of estradiol (E2), and progesterone (P) and P/E2 ratios] of patients undergoing in vitro fertilization/embryo transfer to whom either progesterone in oil or human chorionic gonadotropin (hCG) was administered as luteal support. Seventeen patients were studied in 20 cycles. In 10 randomly assigned cycles 25 mg of intramuscular progesterone in oil was administered daily from the day of embryo transfer (day +4) until day +18. In the other 10 cycles, 1500 IU of hCG was given intramuscularly on days +4, +7, +10, and +13. Even when accounting for the differences in recruitment in the two groups, the hCG-treated group had significantly higher concentrations of serum P (P<0.01) and E2 (P<0.05) during the luteal phase. The luteal P/E2 ratios were higher in the progesterone-treated group because of the lower E2 levels in that group, although the difference was not statistically significant. The ratio of the mean luteal P to the preovulatory serum E2 was significantly higher in the hCG-treated group (P<0.01). There were three clinical pregnancies in the hCG-treated group. We conclude that (1) higher P concentrations are achieved with hCG treatment than with progesterone treatment during the luteal phase; (2) high luteal P/E2 ratios per se may not be an important determinant of implantation; (3) progesterone production by the corpus luteum is not maximal in progesterone-treated cycles; and (4) the usefulness of hCG as a luteal support agent should be further evaluated.

Hyperandrogenism during puberty in the development of polycystic ovary syndrome

The hormonal events of puberty, from adrenarche to menarche and beyond, include the secretion of androgens as well as estrogen and P. This normal pubertal process is briefly reviewed and a physiologic role for pubertal androgens proposed. It is further suggested that the hyperandrogenic state we call polycystic ovary syndrome is a maladaptation of the advantageous role of normal pubertal androgens.

Endogenous luteinizing hormone surges following administration of human chorionic gonadotropin: further evidence for lack of loop feedback in humans.

The existence of inhibitory short- and ultrashort-loop feedback mechanisms for luteinizing hormone (LH), while documented in animals, has been questioned in humans. Since human chorionic gonadotropin (hCG) binds to LH receptors but can be distinguished from LH in immunoassays, it is possible to identify LH surges in the face of exogenously administered hCG. The present study demonstrates LH surges at midcycle in normal volunteers and in women undergoing controlled ovarian hyperstimulation, given hCG. This provides further evidence for lack of loop feedback control of LH secretion in humans.