European journal of endocrinology · 2014
Ovarian macrocysts and gonadotrope-ovarian axis disruption in premenopausal women receiving mitotane for adrenocortical carcinoma or Cushing's disease.
СтатьяНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Salenave Sylvie, Bernard Valérie, Do Cao Christine, Guignat Laurence, Bachelot Anne, Leboulleux Sophie, Droumaguet Céline, Bry-Gauillard Hélène, Pierre Peggy, Crinière Lise, Santulli Pietro, Touraine Philippe, Chanson Philippe, Schlumberger Martin, Maiter Dominique, Baudin Eric, Young Jacques
Аннотация
CONTEXT: Mitotane is an adrenolytic and anticortisolic drug used in adrenocortical carcinoma (ACC), Cushing's disease (CD), and ectopic ACTH syndrome. Its effects on the ovaries are unknown.
OBJECTIVE: To evaluate the ovarian and gonadotrope effects of mitotane therapy in premenopausal women.
PATIENTS: We studied 21 premenopausal women (ACC: n=13; CD: n=8; median age 33 years, range 18-45 years) receiving mitotane at a median initial dose of 3 g/day (range 1.5-6 g/day).
METHODS: Gynecological history was collected and ovarian ultrasound was performed. Four women also underwent ovarian CT or magnetic resonance imaging. Serum gonadotropin, estradiol (E2), androgens, sex hormone-binding globulin (SHBG), and circulating mitotane levels were determined at diagnosis and during mitotane therapy.
RESULTS: In the women included, ovarian macrocysts (bilateral in 51%) were detected after a median 11 months (range: 3-36) of mitotane exposure. The median number of macrocysts per woman was two (range: 1-4) and the median diameter of the largest cysts was 50 mm (range: 26-90). Menstrual irregularities and/or pelvic pain were present in 15 out of 21 women at macrocyst diagnosis. In two women, the macrocysts were revealed by complications (ovarian torsion and hemorrhagic macrocyst rupture) that required surgery. Mitotane therapy was associated with a significant decrease in androstenedione and testosterone levels and a significant increase in LH levels. Serum FSH and E2 levels were also increased, and SHBG levels rose markedly.
CONCLUSIONS: Mitotane therapy causes significant morphological and ovarian/gonadotrope hormonal abnormalities in premenopausal women. Follicular thecal steroid synthesis appears to be specifically altered and the subsequent increase in gonadotropins might explain the development of macrocysts. The mechanisms underlying these adverse effects, whose exact prevalence in this population still needs to be determined, are discussed.
OBJECTIVE: To evaluate the ovarian and gonadotrope effects of mitotane therapy in premenopausal women.
PATIENTS: We studied 21 premenopausal women (ACC: n=13; CD: n=8; median age 33 years, range 18-45 years) receiving mitotane at a median initial dose of 3 g/day (range 1.5-6 g/day).
METHODS: Gynecological history was collected and ovarian ultrasound was performed. Four women also underwent ovarian CT or magnetic resonance imaging. Serum gonadotropin, estradiol (E2), androgens, sex hormone-binding globulin (SHBG), and circulating mitotane levels were determined at diagnosis and during mitotane therapy.
RESULTS: In the women included, ovarian macrocysts (bilateral in 51%) were detected after a median 11 months (range: 3-36) of mitotane exposure. The median number of macrocysts per woman was two (range: 1-4) and the median diameter of the largest cysts was 50 mm (range: 26-90). Menstrual irregularities and/or pelvic pain were present in 15 out of 21 women at macrocyst diagnosis. In two women, the macrocysts were revealed by complications (ovarian torsion and hemorrhagic macrocyst rupture) that required surgery. Mitotane therapy was associated with a significant decrease in androstenedione and testosterone levels and a significant increase in LH levels. Serum FSH and E2 levels were also increased, and SHBG levels rose markedly.
CONCLUSIONS: Mitotane therapy causes significant morphological and ovarian/gonadotrope hormonal abnormalities in premenopausal women. Follicular thecal steroid synthesis appears to be specifically altered and the subsequent increase in gonadotropins might explain the development of macrocysts. The mechanisms underlying these adverse effects, whose exact prevalence in this population still needs to be determined, are discussed.