Influence of Pre-diagnostic Estrogen Fluctuations on the Development of Prolactin-Secreting Macroadenomas or Microadenomas: A Comparative Study Conducted at Hôpital Louis Pradel

Hospices Civils de Lyon1 个研究点分布在 1 个国家目标入组 180 人开始时间: 2026年1月6日最近更新: 2026年1月22日

适应症

试验速览

阶段: 不适用
状态: 招募中
发起方: Hospices Civils de Lyon
入组人数: 180
试验地点: 1
主要终点: number of patients exposed to combined estrogen-progestin contraception

研究概览研究设计入排标准结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

Prolactinomas are the most common pituitary adenomas, representing about two-thirds of clinically relevant cases. Their prevalence is around 50 per 100,000 individuals, with an incidence of 3-5 new cases per 100,000 per year and has been rising in recent decades.

They may increase morbidity and mortality due to several factors:

Hormone hypersecretion: excess prolactin causes galactorrhea, amenorrhea, and infertility.
Mass effect: macroadenomas can compress adjacent structures, leading to headaches, visual loss, or neurological symptoms.
Treatment complications: medical or surgical treatments may carry risks.

A marked sex difference exists, with a male-to-female ratio of 1:5-1:10, and peak diagnosis in women aged 25-44. This disparity disappears after menopause, supporting a potential role of estrogens in tumor development. Lactotrope cells, from which prolactinomas arise, are estrogen-sensitive, unlike other pituitary tumor cells (e.g., somatotrophs, gonadotrophs).

A large 2022 prospective cohort (nurses) suggested a possible association between pituitary adenomas and both combined oral contraceptives (COCs) and hormone therapy (HT). However, limitations included self-reported diagnoses, lack of adenoma characterization, and contradictory findings (association with HT but not consistently with COCs). A 2009 case-control study including all adenomas found no link with hormonal contraception, while older studies from the 1980s assessed high-dose contraceptives no longer in use.

Microprolactinomas are 4-5 times more frequent than macroprolactinomas (≥10 mm). Distinguishing between the two is essential, as they differ in clinical presentation, prognosis, and sex distribution. Macroadenomas are more common in men, possibly due to delayed diagnosis, as symptoms such as decreased libido are less specific, whereas women often present with amenorrhea or galactorrhea. However, studies suggest tumor size is not directly linked to symptom duration, indicating other factors may explain macroadenoma development.

Why some patients develop macro- rather than microadenomas remains unclear. Estrogen exposure is a possible explanation. It is therefore relevant to investigate whether women with macroprolactinomas had greater exposure to endogenous estrogens (early menarche, late menopause, pregnancies, breastfeeding) or exogenous estrogens (contraception, menopausal HT) compared to women with microprolactinomas.

The hypothesis is that women with macroprolactinomas were exposed to higher cumulative levels of estrogens before diagnosis than women with microprolactinomas.

研究设计

研究类型: Observational
观察模型: Other
时间视角: Prospective

入排标准

年龄范围: 18 Years 至 —（Adult, Older Adult）
性别: Female
接受健康志愿者: 否

入选标准

•Female patients aged ≥ 18 years at recruitment (diagnosis may have occurred before age 18).
•Diagnosis of a prolactin-secreting macroadenoma established between January 2013 and December
•The diagnosis may have been made either in the Endocrinology Department of Hôpital Louis Pradel or by another medical team, whether within or outside the hospital setting. However, follow-up or part of the follow-up must have been performed in the Endocrinology Department of Hospices Civils de Lyon (HCL)
•Diagnosis established by : A hypothalamic-pituitary MRI centered on the sella turcica, performed with gadolinium injection, including fine T1-weighted coronal and sagittal slices (1.5-3 mm), showing an adenoma with at least one axis measuring > 10 mm, AND Serum prolactin > 100 µg/L, or 24-100 µg/L with either a favorable response to medical therapy or histopathological confirmation after surgery.
•Ability to understand the study and provide informed non-opposition.
•Inclusion Criteria of controls :
•Female patients aged ≥ 18 years at the time of recruitment (diagnosis may have occurred before age 18).
•Diagnosis of a prolactin-secreting microadenoma established between January 2013 and December
•The diagnosis may have been made in any medical center, but follow-up or part of the follow-up must have been carried out in the Endocrinology Department of Hôpital Louis Pradel.
•Diagnosis must be based on: A hypothalamic-pituitary MRI centered on the sella turcica, performed with gadolinium injection, including fine T1-weighted coronal and sagittal slices (1.5-3 mm), showing a prolactin-secreting adenoma with all axes measuring < 10 mm, AND A biological assessment performed outside any condition likely to bias results (significant stress, physical exertion, pregnancy, or intake of hyperprolactinemia-inducing drugs unrelated to prolactinoma treatment), showing serum prolactin > 24 µg/L.
•Ability to understand the nature and implications of the study and to provide informed non-opposition to participation.

排除标准

•Presence of a non-secreting macroadenoma.
•History of isolated hyperprolactinemia or an isolated pituitary lesion documented prior to 2013, without subsequent direct diagnosis of prolactinoma.
•Presence of a known genetic abnormality or a genetic syndrome predisposing to the development of a prolactin-secreting adenoma.
•Exclusion Criteria of controls :
•Presence of a non-secreting microadenoma.
•Uncertain diagnosis of adenoma with an ongoing therapeutic trial.
•Isolated hyperprolactinemia without evidence of adenoma.
•Hyperprolactinemia or pituitary lesion without hyperprolactinemia documented prior to 2013, without subsequent direct diagnosis of prolactinoma.
•Presence of a known genetic abnormality or a genetic syndrome predisposing to the development of a prolactin-secreting adenoma