Wallenberg Laboratory for Cardiovascular and Metabolic Research, Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, S-413 45 Gothenburg, Sweden.
Department of Medicine, Hospital of Halland, S-434 80 Kungsbacka, Sweden.
J Clin Endocrinol Metab. 2024 Oct 15;109(11):2967-2978. doi: 10.1210/clinem/dgae197.
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.
To quantify sex steroids in women with hypopituitarism by a high-sensitivity assay.
Using a combination of clinical and biochemical criteria, women with hypopituitarism (n = 104) who started GH replacement in 1995 to 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.
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 ACTH deficiency had markedly lower concentrations of all sex hormones than those without ACTH deficiency.
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.
患有垂体功能减退症的女性仍然存在较高的发病率和死亡率。有人认为，性激素替代不足是一个促成因素，但患有垂体功能减退症的女性的性激素水平尚未得到全面描绘。
通过高灵敏度测定法对患有垂体功能减退症的女性的性激素进行定量。
使用临床和生化标准相结合的方法，对 1995 年至 2014 年期间在一家中心开始接受 GH 替代治疗的患有垂体功能减退症的女性（n=104）进行分类，分为性腺功能正常或患有促性腺激素低下性性腺功能减退症（HH）。以人群为基础的女性队列（n=288）作为对照组。将性腺功能正常的女性和对照组分为绝经前/绝经后，将 HH 女性分为年轻/年长（≤52 岁或>52 岁）。使用经验证的液相色谱-串联质谱法测定脱氢表雄酮（DHEA）、雄烯二酮、睾酮、二氢睾酮、孕酮、17α-羟孕酮、雌二醇和雌酮。
在绝经前/年轻和绝经后/年长的女性中，与对照组相比，HH 女性的性激素前体（DHEA、雄烯二酮）和雄激素（睾酮和二氢睾酮）水平较低。孕酮、17α-羟孕酮、雌酮和雌二醇也呈现出相似的模式。伴有 ACTH 缺乏的 HH 女性的所有性激素浓度明显低于无 ACTH 缺乏的女性。
本研究首次表明，无论年轻还是年长的 HH 女性均存在广泛而严重的性激素缺乏，尤其是那些伴有促性腺激素和 ACTH 缺乏的女性。患有垂体功能减退症的女性的低性激素水平对健康的影响需要进一步研究，并且伴有促性腺激素和 ACTH 缺乏的女性应成为性激素替代干预研究的优先群体。
