R. Jeffrey Chang

Treatment of severe androgen excess due to ovarian hyperthecosis with a long-acting gonadotropin-releasing hormone agonist☆

A 31-year-old nulligravid patient presented with irregular menses, severe hirsutism, and infertility. Evaluation revealed marked increases of serum androstenedione and testosterone levels and a possible ovarian mass. At operation a cystic teratoma was removed from the left ovary and bilateral wedge resection revealed severe ovarian hyperthecosis. After operation only a transient decrease of androstenedione and testosterone was noted and the patient failed to ovulate or improve clinically. Subsequently a long-acting gonadotropin-releasing hormone agonist was administered daily for 6 months, which reduced circulating delta 4-steroids and estrogens to levels approximating those of castrated women. Immediately after discontinuation of treatment, ovulation induction was successfully achieved with human menopausal gonadotropin. This report introduces a new therapeutic approach to the problem of severe ovarian hyperthecosis and may provide an opportunity for childbearing in these patients.

Tumor-level serum testosterone associated with human immunodeficiency virus lipodystrophy syndrome.

BACKGROUND: Human immunodeficiency virus (HIV) lipodystrophy syndrome consists of insulin resistance, hyperlipidemia, increased waist-to-hip ratios, and relative hyperandrogenemia, which resembles polycystic ovary syndrome. CASE: A 30-year-old HIV-positive multipara with lipodystrophy syndrome had an elevated level of serum total testosterone (244 ng/dL) in the tumor range. CONCLUSION: In HIV lipodystrophy syndrome, marked elevations of total serum testosterone in the range reserved for androgen-producing tumors may occur. The elevated testosterone levels are derived from the ovary and are responsive to gonadotropin suppression.

Hypothalamic-Pituitary Dynamics in Polycystic Ovary Syndrome

Polycystic ovary syndrome (PCOS) is characterized by chronic anovulation and hyperandrogenism. Despite our knowledge on the pathophysiology of this condition, the exact etiology remains elusive. An altered function of each of the following has been suggested as the initiating etiologic factor: the hypothalamic-pituitary unit, the ovary, the adrenal, and general metabolic control. This chapter focuses on some relevant observations of altered hypothalamic-pituitary dynamics in PCOS.

Effects of Gonadotropin-Releasing Hormone (GnRH) Agonist on Pituitary and Ovarian Responses to Pulsatile GnRH Therapy in Polycystic Ovarian Disease

Nine clomiphene citrate-resistant polycystic ovarian disease (PCOD) patients received intravenous gonadotropin-releasing hormone (GnRH) pulses before and immediately after 1 month of GnRH agonist (GnRH-a) therapy. Circulating gonadotropin and ovarian steroid levels, as well as follicular development, were measured throughout therapy. Results were compared with those obtained from five hypogonadotropic patients treated with GnRH pulses only who ovulated during six of seven treatment cycles. Only two PCOD patients ovulated normally with GnRH pulses before GnRH-a therapy. Aberrant gonadotropin and ovarian steroid secretory patterns were noted in the others. After GnRH-a, gonadotropin and ovarian steroid hormone levels were similar to those of the hypogonadotropic patients. Subsequent secretory responses to GnRH pulses were partially normalized. However, only two additional PCOD patients ovulated.

Origin of Serum Progestins in Polycystic Ovarian Disease

The glandular origin of excess circulating steroid hormones in women with polycystic ovarian disease has been difficult to establish with previously described perturbation techniques. Recently it was demonstrated that daily administration of a potent gonadotropin-releasing hormone agonist achieves complete and reversible suppression of ovarian steroid secretion. To examine the source of C-21 steroid hormones, circulating levels were measured before and after administration of the same agonist in polycystic ovarian disease subjects and normal control subjects. Serum levels of these hormones were also determined after administration of dexamethasone and adrenocorticotropic hormone (ACTH) as well as bilateral oophorectomy. Subjects with polycystic ovarian disease exhibited significant elevations of serum pregnenolone, 17OH-pregnenolone, and 17OH-progesterone by comparison with normal control subjects. The glandular origins of the excess levels of pregnenolone and 17OH-pregnenolone were more difficult to determine and appear to be different from that of 17OH-progesterone.

Circulating Levels of Plasma Adrenocorticotropin in Polycystic Ovary Disease

Excessive adrenal androgen production contributes to hyperandrogenism in polycystic ovarian disease (PCO). This study was performed to determine the concentration of basal plasma ACTH in PCO patients and normal women and correlate its level with that of circulating adrenal androgen. In PCO patients, significant increases in serum testosterone, androstenedione, and dehydroepiandrosterone sulfate were noted compared to levels in normal women. The mean circulating plasma ACTH in PCO patients (22 +/- 2 pg/ml) was not different from that in normal controls (20 +/- 2 pg/ml). The mean ratio of dehydroepiandrosterone sulfate to ACTH in individual PCO patients was significantly greater than that in normal subjects, whereas the cortisol to ACTH ratio was similar in both groups. These results suggest that increased adrenal androgen production in PCO patients is not due to abnormal ACTH secretion but arises from either altered adrenal responsiveness to ACTH or abnormal adrenal stimulation by a factor(s) other than ACTH.