背景:患有垂体功能减退症的女性发病率和死亡率仍然增加。性类固醇替代不足被认为是一个促成因素,但是垂体功能减退症女性的性类固醇水平尚未得到全面的定位。
目的:通过高灵敏度测定来定量女性垂体功能减退症患者的性类固醇。
方法:结合临床和生化标准,1995-2014年在一个中心开始使用生长激素替代治疗的垂体功能减退女性(n=104)被归类为性腺功能低下或性腺功能减退(HH).以人群为基础的女性队列(n=288)作为对照。Eugonadal妇女和对照组被归类为绝经前/绝经后和HH妇女被归类为年轻/老年(≤或>52岁)。脱氢表雄酮(DHEA),雄烯二酮,睾丸激素,双氢睾酮,黄体酮,17αOH-孕酮,雌二醇和雌酮通过有效的液相色谱-串联质谱分析。
结果:在绝经前/年轻和绝经后/老年妇女中,患有HH的女性性激素前体水平较低(DHEA,雄烯二酮)和雄激素(睾酮和二氢睾酮)比对照组。孕酮,17αOH-孕酮,雌酮和雌二醇表现出相似的模式。患有HH和促肾上腺皮质激素(ACTH)缺乏症的妇女的所有性激素浓度明显低于没有ACTH缺乏症的妇女。
结论:这项研究首次证明了年轻和老年女性患有HH的广泛和严重的性类固醇缺乏症,特别是在促性腺激素和ACTH缺乏的患者中。低性别类固醇水平对垂体功能减退症女性的健康影响需要进一步研究,患有促性腺激素和ACTH缺乏症的女性应作为性激素替代干预研究的优先群体。
BACKGROUND: Women with hypopituitarism remain at increased risk of morbidity and mortality. Insufficient replacement of sex steroids has been suggested as a contributing factor, but sex steroid levels in women with hypopituitarism have not been comprehensively mapped.
OBJECTIVE: To quantify sex steroids in women with hypopituitarism by a high-sensitivity assay.
METHODS: Using a combination of clinical and biochemical criteria, women with hypopituitarism (n = 104) who started growth hormone replacement 1995-2014 at a single center were categorized as eugonadal or having hypogonadotropic hypogonadism (HH). A population-based cohort of women (n = 288) served as controls. Eugonadal women and controls were categorized as pre-/postmenopausal and HH women as younger/older (≤ or >52 years). Dehydroepiandrosterone (DHEA), androstenedione, testosterone, dihydrotestosterone, progesterone, 17αOH-progesterone, estradiol and estrone were analyzed by a validated liquid chromatography-tandem mass spectrometry assay.
RESULTS: Among both premenopausal/younger and postmenopausal/older women, women with HH had lower levels of sex steroid precursors (DHEA, androstenedione) and androgens (testosterone and dihydrotestosterone) than controls. Progesterone, 17αOH-progesterone, estrone and estradiol showed similar patterns. Women with HH and adrenocorticotropic hormone (ACTH) deficiency had markedly lower concentrations of all sex hormones than those without ACTH deficiency.
CONCLUSIONS: This study demonstrates for the first time a broad and severe sex steroid deficiency in both younger and older women with HH, particularly in those with combined gonadotropin and ACTH deficiency. The health impact of low sex steroid levels in women with hypopituitarism requires further study and women with combined gonadotropin and ACTH deficiency should be a prioritized group for intervention studies with sex hormone replacement.