Characteristic Features of Reproductive Hormone Profiles in Late Adolescent and Adult Females with Complete Androgen Insensitivity Syndrome

Abstract

Little is known about gonadotropins and sex steroid levels in postpubertal women with complete androgen insensitivity syndrome (CAIS). In order to define reproductive hormone profiles in women with CAIS and intact gonads, 42 postpubertal females with proven CAIS (age range 14-50 years) with testes in situ were examined. Reproductive hormone values [testosterone (T), estradiol (E2), sex hormone-binding globulin (SHBG), luteinizing hormone (LH), follicle-stimulating hormone (FSH)] were assessed by commercially available immunoassays. In women with CAIS, LH levels (median 18.5 IU/l, range 5.5-51.1 IU/l) were elevated above the usual adult reference ranges, whereas FSH values (3.5 IU/l, 0.4-16.3 IU/l) were not. Basal T (20 nmol/l, 6-52 nmol/l) and E2 values (113 pmol/l; 18-257 pmol/l) were found in the usual adult male reference ranges; SHBG levels (53 nmol/l, 15-180 nmol/l) were in the adult female reference range. Calculated free androgen indices (Tx10³/SHBG: 380, 114-863) and aromatization indices (E2/T: 0.052, 0.020-0.196) did not differ from the reference ranges for adult men given in the literature (Tx10³/SHBG: 315-936; E2/T: 0.03-0.07). Reproductive hormone profiles in women with CAIS do not follow the usual male/female pattern, suggesting a specific postpubertal hormone milieu. Albeit calculation of CAIS-specific reference ranges requires larger series and standardization of laboratory methods, these results may be a prerequisite for the identification of pathologic hormone patterns in women with CAIS and gonads in situ. The present data will also be useful to monitor hormone replacement therapy in individuals with removed gonads.

Novel Familial Variant of the Desert Hedgehog Gene: Clinical Findings in Two Sisters with 46,XY Gonadal Dysgenesis or 46,XX Karyotype and Literature Review

“…A histological report (year 1961) described a dysgenetic-like testis structure with seminiferous tubules containing only Sertoli cells, but slides were not available for a re-examination; remnants of müllerian structures were also found (immature Fallopian tubes but not uterus). When she was 18 years old, she was diagnosed with complete androgen insensitivity syndrome because of primary amenorrhea and 46,XY karyotype, but clinical findings (absence of breast development, normal pubic and axillary hair) and endocrine data (LH, 105 IU/L; FSH, 210 IU/L; both testosterone and 17β-estradiol undetectable) were not consistent with such a diagnosis [21, 22]. At the age of 20 years, this woman underwent surgery for acute appendicitis and the right gonad was removed.…”

Gonadectomy in Complete Androgen Insensitivity Syndrome: Why and When?

“…Recently, we have examined the very specific endocrine profiles of women with CAIS [Doehnert et al, 2015]. A conclusion towards "irregular" or "abnormal" cannot be made in this condition as the usual male/female pattern is lacking and therefore a reference population does not exist.…”

“…The underlying condition is a peripheral resistance towards all androgenic steroids due to a mutation of the androgen receptor. This leads to a very specific endocrine environment with slightly elevated LH levels and FSH, testosterone, and estradiol values in the male reference range despite pubertal feminization [Doehnert et al, 2015].The current debate on the prophylactic gonadectomy versus the saving of the testes is inflamed by several points. As reviewed by Cools et al [this issue], an increased risk for testicular germ cell tumors (GCT) has been demonstrated.…”

Mismatch between fetal sexing and birth phenotype: a case of complete androgen insensitivity syndrome

“…A typical hormone profile for CAIS patients has the following features: low LH/FSH and elevated testosterone levels at birth, low LH/FSH and low testosterone levels at minipuberty, low LH/FSH and low testosterone levels during infancy and childhood, and elevated LH, normal or mild elevated FSH, and elevated testosterone levels together with an elevated estradiol levels for male reference range after the onset of puberty [11,31,32]. A recent publication reported that basal testosterone and estradiol levels in postpubertal women with CAIS were found in the usual adult male reference ranges [33]. It is necessary to understand the disease-specific hormone profile at each developmental stage for accurate diagnosis.…”