ProlactinomaOEMacroPrLNCT07268183
How Estrogen Fluctuations Before Diagnosis Affect the Size Prolactin-secreting Tumors
An observational study of Prolactinoma and Macroprolactinoma, run by Hospices Civils de Lyon at 1 site in France.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Prolactinoma, Macroprolactinoma
- What is being tested?
- Standardized questionnaire
- How many people
- 171 participants
- Where
- 1 siteFrance
- Study dates
- 6 Jan 2026to 13 Jan 2026
- Phase
- Observational
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Study population: Patients included in this study will be identified from the COLLEMARA database, used within the Hospices Civils de Lyon. This database, specifically dedicated to rare diseases, provides a structured registry of patients followed for rare pituitary disorders, such as prolactinomas. For the purpose of this study, the COLLEMARA database will be used solely to identify eligible patients, based on the coded diagnosis of "prolactinoma." The study population will consist of female patients whose diagnosis was made between 2013 and 2023 and who meet the other inclusion criteria. A total of 180 patients will be included: 60 in the case group ("macroprolactinomas") and 120 in the control group ("microprolactinomas").
Who may be able to join
- 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 2023. 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.
- 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 2023. 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.
Who cannot join
- 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.
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Influence of Pre-diagnostic Estrogen Fluctuations on the Development of Prolactin-Secreting Macroadenomas or Microadenomas: A Comparative Study Conducted at Hôpital Louis Pradel
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:
Read more
- 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.
- Conditions
- Prolactinoma, Macroprolactinoma
- Being tested
- Standardized questionnaire
- Keywords
- Prolactinoma, Macroprolactinoma, pituitary adenomas, lactotroph adenoma, risk factor, microprolactinoma, Combined hormonal contraception, combined oral contraception, estrogen impact
- Medical subject headings
- Prolactinoma, Pituitary Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Standardized questionnaireOther
The intervention is a questionnaire which will be administered only if informations available on medical files are not sufficient.
1 mounth before questionning our cases and controls, they will receive a participant information note.
It will be administered primarily by telephone. If the patient prefers not to answer by telephone, a paper version will be mailed to her. In this case, she will have up to two months to return the completed questionnaire by post.
The questionnaire will collect detailed information on potential exposures to estrogens and reproductive history.
| Study group | Role | What they receive |
|---|---|---|
| Women with a macroprolactinoma | Women with prolactin-producing macroadenomas diagnosed between 2013 and 2023 Followed by the Hospices Civiles de Lyon, Hôpital Cardiologique of Bron. Receives: Other: Standardized questionnaire | |
| Women with a microprolactinoma | Women with prolactin-producing microadenomas diagnosed between 2013 and 2023 Followed by the Hospices Civiles de Lyon, Hôpital Cardiologique of Bron. Receives: Other: Standardized questionnaire |
What is being measured
The primary outcome is the main question the study is designed to answer.
number of patients exposed to combined estrogen-progestin contraception
Identify the estrogen-dependent risk factor
Measured: week 4
number of patients exposed to menopausal hormone therapy
Identify the estrogen-dependent risk factor
Measured: week 4
number of patients exposed to progestin-only treatment
Identify the estrogen-dependent risk factor
Measured: week 4
number of patients exposed to Ovarian Stimulation
Identify the estrogen-dependent risk factor
Measured: week 4
Age at First Use of Hormonal Contraception
Identify the estrogen-dependent risk factor
Measured: week 4
Age at Menarche
Identify the estrogen-dependent risk factor
Measured: week 4
Age at Menopause
Identify the estrogen-dependent risk factor
Measured: week 4
Age at First Live Birth
Identify the estrogen-dependent risk factor
Measured: week 4
Nulliparity
Identify the estrogen-dependent risk factor
Measured: week 4
Number of Pregnancies Carried to Viability
Identify the estrogen-dependent risk factor
Measured: week 4
Exposure to Breastfeeding defined as the total cumulative duration of breastfeeding across all pregnancies, expressed in months. • None: 0-1 month • Moderate: 1-12 months • High: >12 months
Identify the estrogen-dependent risk factor
Measured: week 4
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Dec 2025
- Study start6 Jan 2026
- Primary completion13 Jan 2026
- Study completion13 Jan 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for ProlactinomaStudies of the same condition, open and under way.
- More trials run by Hospices Civils de LyonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Other
- Time perspective
- Prospective
- Enrolment
- 171 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hospices Civils de Lyon
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07268183
- Sponsor's protocol ID
- 69HCL25_0853
- Acronym
- OEMacroPrL
- Status last verified
- Jan 2026
- First submitted
- 19 Nov 2025
- Last updated
- 23 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No