Virilization In Women Research Articles

Diagnostic pitfalls in ovarian androgen-secreting tumors in postmenopausal women with rapidly progressed severe hyperandrogenism.

Sex cord-stromal neoplasms of the ovary are rare tumors and a very infrequent cause of androgen excess and virilization in women. We report two cases of postmenopausal women with rapidly progressive signs of virilization and negative or indeterminate imaging for pelvic masses. Both patients underwent a complete hormone profile, inconclusive transvaginal ultrasound and contrast-enhanced abdominopelvic computed tomography. Serum hormone analysis revealed for both cases a marked increase in serum total testosterone (T). In the first woman, Δ-4 androstenedione (Δ-4 A), dehydroepiandrosterone-sulfate (DHEA-S) and cortisol levels were in a normal range for age. In the second, Δ-4 A and DHEA-S levels were below the reference range. For both women, an ovarian source of androgens was suspected and bilateral laparoscopic oophorectomy was performed. Ovarian histology demostrated bilateral Leydig cell tumor (LCT) in the first case and bilateral ovarian thecoma in the second. After surgery, total testosterone returned to normal levels and clinical symptoms subsided. In cases of postmenopausal androgen excess, physicians must rule out relatively rare androgen-producing tumors originating from the adrenals or ovaries. Regardless of imaging evaluation, our report highlights the importance of prompt and careful clinical and hormonal evaluation to ensure appropriate and timely treatment for the patient.

Ovarian Sertoli Leydig cell tumors: a single institution series of predominantly postmenopausal women.

e17052Background: Sertoli Leydig cell tumors (SLCT) of the ovary are rare, and usually present as progressive virilization in women in their second to third decade of life. Less than 10% of patient...

Analogs and Antagonists of Male Sex Hormones

The steroid testosterone is the major circulating sex hormone in males and is the prototype for the androgens, the anabolic agents, and androgen antagonists. Endogenous androgens are biosynthesized from cholesterol; the majority of the circulating androgens are produced in the testes under the stimulation of luteinizing hormone (LH). The reduction of testosterone to dihydrotestosterone is necessary for androgenic actions of testosterone in many androgen target tissues such as the prostate; the oxidation of testosterone by the enzyme aromatase produces estradiol. The androgenic actions of testosterone and dihydrotestosterone are due to their binding to the androgen receptor, followed by nuclear localization, dimerization of the receptor complex, and binding to specific DNA sequences. This binding of the homodimer to the androgen response element leads to gene expression, stimulation, or repression of new mRNA synthesis, and subsequent protein biosynthesis. The synthetic androgens and anabolics were prepared to impart oral activity to the androgen molecule, to separate the androgenic effects of testosterone from its anabolic effects, and to improve on its biological activities. Novel nonsteroidal androgens, termed selective androgen receptor modulators, were developed to impart agonist activity in selective tissues. Drug preparations are used for the treatment of various androgen-deficient diseases and for the therapy of diseases characterized by muscle wasting and protein catabolism. Androgen antagonists include antiandrogens, which block interactions of androgens with the androgen receptor, and inhibitors of androgen biosynthesis and metabolism. Such compounds have therapeutic potential in the treatment of acne, virilization in women, hyperplasia and neoplasia of the prostate, and baldness. Keywords: androgens; testosterone; dihydrotestosterone; anabolics; antiandrogens; selective androgen receptor modulators; 5α-reductase inhibitors

Voice problems due to virilization in adult women with congenital adrenal hyperplasia due to 21‐hydroxylase deficiency

Congenital adrenal hyperplasia (CAH) is an autosomal recessive inherited disorder in which the lack of 21-hydroxylase results in cortisol and aldosterone insufficiency and an overproduction of adrenal androgens. High levels of androgens in women may cause virilization of the larynx and a masculine voice. The purpose of the present study was to investigate subjective voice problems due to virilization in women with CAH. Participants were 42 women with CAH between 25 and 71 years of age, and 43 age-matched female healthy control subjects. All patients, but two, were in good disease control. A validated Swedish version of the Voice Handicap Index (VHI) and questions related to voice virilization were used. Endocrine data were obtained from medical files. Patients scored significantly higher on VHI when the results were divided into no/mild, moderate and severe voice handicap as compared with the control subjects. They rated significantly higher for 'dark voice' and for 'being perceived as a man on the phone' compared with controls. Seven per cent of the women with CAH had voice problems clearly related to voice virilization. High ratings of dark voice were significantly associated with long periods of under-treatment with glucocorticoids and higher bone mineral density but not with severity of mutation. Subjective voice problems due to voice virilization may occur in women with CAH. This further emphasizes the importance of avoiding long periods of increased androgen levels to prevent irreversible voice changes. For these patients, we recommend referral to voice assessment and treatment.

Breakthrough in cachexia treatment through a novel selective androgen receptor modulator?!

Cachexia, and particularly the loss of metabolically active lean tissue, leads to increased morbidity and mortality in affected patients. An impairment of strength and functional status is usually associated with cachexia. A variety of anabolic and appetite-stimulating agents have been studied in patients with cachexia caused by various underlying diseases. Overall, these studies have demonstrated that treatment can increase body weight and/or lean body mass. However, these therapies may have severe side effects, particularly when utilizing testosterone and related anabolic steroids targeting the androgen receptor. These side effects include cardiovascular problems, prostate hyperplasia and cancer in men, as well as virilization in women.

The degree of external genitalia virilization in girls with 21‐hydroxylase deficiency appears to be influenced by the CAG repeats in the androgen receptor gene

Women with 21-hydroxylase deficiency present much variability in external genitalia virilization, even among those with similar impairments of 21-hydroxylase (21OH) activity. To evaluate if the number of CAG (nCAG) repeats of the androgen receptor gene influences the degree of external genitalia virilization in women with CYP21A2 mutations, grouped according to impairment of 21OH activity. The nCAG was determined in 106 congenital adrenal hyperplasia (CAH) patients and in 302 controls. The patients were divided, according to their CYP21A2 genotypes, into Groups A and B, which confer total and severe impairment of 21OH activity, respectively. The inactivation pattern of the X-chromosome was studied through genomic DNA digestion with Hpa II. The CAG repeat region was amplified by polymerase chain reaction (PCR) and analysed by GeneScan. The nCAG and the frequency of severe skewed X-inactivation did not differ between normal women and patients. The nCAG median in genotype A was 20.7 (IQR 2.3) for Prader I + II, 22.5 (3.6) for Prader III and 21 (2.9) for Prader IV + V (P < 0.05 for Prader III and Prader IV + V). The nCAG median in genotype B was 21.3 (1.1) for Prader I + II, 20.5 (2.9) for Prader III and 22 (2.8) for Prader IV + V (P > 0.05). A significant difference was found regarding the nCAG median in patients presenting Prader III from genotypes A and B. We observed great variability in the degree of external genitalia virilization in both CYP21A2 genotypes, and we showed that the CAG repeats of the androgen receptor gene influences this phenotypic variability.

Randomized trial of tamoxifen alone or combined with fluoxymesterone as adjuvant therapy in postmenopausal women with resected estrogen receptor positive breast cancer. North Central Cancer Treatment Group Trial 89-30-52

This clinical trial evaluated the addition of fluoxymesterone (Flu) to tamoxifen (Tam) in women with resected early stage breast cancer and attempted to corroborate the findings of superiority for the combination over Tam alone seen in a previous randomized trial in metastatic disease. Postmenopausal women with early stage breast cancer that was known to be estrogen receptor (ER) positive were randomized to treatment with Tam (20 mg per day orally for 5 years) alone or combined with Flu (10 mg orally twice per day for 1 year). The primary endpoint was relapse-free survival (RFS) defined as local-regional or distant recurrence including ductal carcinoma in situ of the ipsilateral, but not contralateral breast, and death from any cause. There were 541 eligible patients entered between 1991 and 1995 and the treatment arms were balanced with respect to patient characteristics. The median follow up of patients still alive was 11.4 years. No significant difference was found between Tam plus Flu and Tam alone in terms of RFS or overall survival. The adjusted hazard ratio (Tam+Flu/Tam) for relapse or death without relapse was estimated to be 0.84 (95% CI: 0.64-1.10) and that for death was 0.89 (95% CI: 0.67-1.18). As expected there was more virilization in women who received Flu. This clinical trial did not demonstrate superiority of Tam plus Flu over Tam alone as adjuvant therapy for postmenopausal women with resected early breast cancer known to be ER positive.

Anabolic steroids in athletics: How well do they work and how dangerous are they?

The use of anabolic drugs by athletes who wish to increase lean body mass and improve muscular strength is widespread, especially among elite weight-trained athletes. The current regimens used for steroid doping include combinations of injectable and oral preparations of steroids at doses 10 to 40 times greater than those prescribed therapeutically. Most of the scientific studies of steroid use by healthy male athletes have used steroid doses substantially lower than those used by many athletes. Analysis of these studies suggests that most persons will gain an average of 2.2 kg of lean body weight during steroid administration but that there exist great individual differences in strength changes induced by steroids. Approximately 50% of the investigations show significant improvements in strength measurements with steroid treatment, whereas the remainder show indefinite effects. There is no substantial evidence to support the use of anabolic steroids for improving aerobic work capacity. Anabolic steroids cause interrupted growth and virilization in children, birth defects in the unborn, severe virilization in women, and testicular atrophy and reduced blood levels of gonadotropins and testosterone in adult males. In addition, the oral preparations of anabolic steroids are associated with liver dysfunction, including carcinoma and peliosis hepatis, and a number of other disorders including unpredictable changes in mood, aggression, and libido. Although there have been only rare reports of severe or life-threatening side effects in athletes who have abused steroids, such side effects may not appear obvious until 20 years or more of widespread steroid abuse.

A comparison of androgen production and clearance in hirsute and obese women

Virilization in women is associated with increased production of testosterone as well as a variety of androgenic prehormones, including androstenedione, androstenediol, DHEA, DHEA-sulfate, dihydrotestosterone and androstanediol. Of these hormones, it is likely that testosterone is the androgen which initiates a series of androgen-receptor mediated events resulting in stimulation of 5α reductase in the skin and hair follicles, producing dihydrotestosterone locally. The metabolism of testosterone to dihydrotestosterone within the hair follicle results in increased clearance of testosterone, however at the expense of hair follicle stimulation. Increased 5α reductase of the skin and hair allows other prehormones to be metabolized to dihydrotestosterone and androstanediol, further stimulating the hair follicle (multiplier effect). In obese women, androgen production rates are elevated and SHBG levels are depressed, in many cases to the same magnitude as that observed in hirsute women. Increased androgen production rates in obesity, however, are associated with major increases in clearance rates of these androgens. Resultant androgen blood levels are even lower than observed in the non-obese population. It appears likely that adipose tissue is the site of the increased clearance rates and metabolism of prehormones to dihydrotestosterone and androstanediol. A delicate balance likely exists between production and clearance of these biologically active hormones. Minor aberrations in this balance may result in the increased incidence of hirsutism seen in the obese female population.