What is the cause of recurrent nipple discharge in a 48-year-old female patient with a history of pelvic pain, upcoming surgery, and inverted right nipple, who is presenting for a Depo (medroxyprogesterone acetate) injection and reports spotting that started on Wednesday?

From the Guidelines

This 48-year-old female patient requires a breast surgical consultation to evaluate the recurrent right nipple discharge, and should undergo diagnostic imaging including a repeat mammogram and breast ultrasound to rule out underlying pathology such as intraductal papilloma, ductal ectasia, or malignancy, as recommended by the American College of Radiology Appropriateness Criteria 1. The patient's history of pelvic pain, previous doctor's visit in Simolone on May 5,2025, and upcoming surgery scheduled for July 29th are noted, but are not directly relevant to the current concern of nipple discharge. The patient's mammogram in February is also noted, but given the recurrence of nipple discharge, a repeat mammogram and breast ultrasound are necessary to evaluate for any changes or underlying pathology, as suggested by the ACR Appropriateness Criteria 1. Some key points to consider in the evaluation of nipple discharge include:

• The type of nipple discharge, with pathologic discharge being more concerning for underlying malignancy 1
• The patient's age, with women over 40 requiring mammography or digital breast tomosynthesis (DBT) as the initial examination, and ultrasound as a complementary examination 1
• The importance of monitoring the discharge characteristics (color, consistency, bloody components) and reporting any changes before the surgical consultation 1 The patient can proceed with her scheduled Depo-Provera injection today, as the spotting is a common side effect, but should be advised that hormonal contraception might occasionally influence breast symptoms, as noted in the patient's history of spotting since Wednesday. Given the potential for underlying pathology, it is essential to prioritize the patient's breast health and proceed with the recommended diagnostic imaging and surgical consultation, as the rate of malignancy associated with pathologic nipple discharge can be as high as 11% to 16% 1.

From the FDA Drug Label

Medroxyprogesterone acetate inhibits (in the usual dose range) the secretion of pituitary gonadotropin which, in turn, prevents follicular maturation and ovulation. Because of its prolonged action and the resulting difficulty in predicting the time of withdrawal bleeding following injection, medroxyprogesterone acetate is not recommended in secondary amenorrhea or dysfunctional uterine bleeding.

The patient is experiencing spotting and nipple discharge, but the provided drug labels do not directly address these symptoms in relation to medroxyprogesterone acetate.

• The labels discuss the effects of medroxyprogesterone acetate on the endometrium and menstrual cycle, but do not provide information on nipple discharge or spotting as side effects.
• The labels also mention that medroxyprogesterone acetate can affect various laboratory tests, but do not provide guidance on managing spotting or nipple discharge in patients taking the medication 2, 2.

From the Research

Patient Presentation

• The patient is a 48-year-old female presenting for follow-up with a history of pelvic pain.
• She has an upcoming surgery scheduled for July 29th.
• The patient had completed a mammogram in February and had reported nipple discharge, which had resolved after antibiotic treatment.
• However, she now reports nipple discharge on the right nipple, which she states has been inverted her whole life.
• The patient is also experiencing spotting, which started on Wednesday, and is due for a repeat Depo injection.

Nipple Discharge Evaluation

• According to 3, the initial evaluation of pathologic nipple discharge involves mammography and ultrasound.
• 4 suggests that a thorough history and physical exam can help differentiate physiologic from pathologic nipple discharge.
• 5 states that the primary goal of evaluation and management is to separate patients with pathologic causes of discharge from those with benign or physiologic causes.
• 6 found that the combination of digital mammography and ultrasound had a 93% sensitivity and a 98% negative predictive value (NPV) for malignancy, while contrast-enhanced MRI (CE-MRI) had a 100% sensitivity and a 100% NPV for malignancy.

Imaging Recommendations

• 3 recommends MRI as a preferred imaging modality for evaluating pathologic nipple discharge due to its increased sensitivity, specificity, and patient comfort.
• 4 suggests that mammography and ultrasound are widely available for initial work-up, while MRI has become more commonplace in recent years.
• 6 found that CE-MRI can detect malignancies not detected on mammography or ultrasound and can obviate the need for surgical duct excision.

Management Considerations

• 4 introduces a flow chart as an overview for step-by-step management of nipple discharge.
• 5 emphasizes the importance of a thoughtful and prudent approach to nipple discharge to alleviate patient anxiety and efficiently define the underlying etiology.
• 6 suggests that the combination of mammography and ultrasonography can detect most breast malignancies associated with nipple discharge, while CE-MRI can detect the remaining malignancies.