What hormone could contribute to nipple discomfort?

Hormones Contributing to Nipple Discomfort

Prolactin is the primary hormone that can contribute to nipple discomfort, particularly through hormone-induced hyperprolactinemia causing nipple discharge, periductal inflammation, and breast pain. 1

Prolactin as the Primary Culprit

Elevated prolactin levels directly cause nipple and breast symptoms through multiple mechanisms:

• Hyperprolactinemia induces nipple discharge, which is a well-recognized presentation in transgender women on feminizing hormone therapy and can occur in any patient with elevated prolactin 1
• Prolactin promotes periductal and intraductal sterile inflammation, leading to nonpuerperal mastitis that manifests as burning pain behind the nipple, particularly in the subareolar area 2, 3
• In patients with nonpuerperal mastitis (duct ectasia), 26.8% exhibit transiently elevated prolactin levels during inflammation (mean 42 ± 22 μg/L), while 20.4% present with more severe hyperprolactinemia (78 ± 56 μg/L) 2

Clinical Algorithm for Evaluation

When evaluating nipple discomfort, measure serum prolactin levels in the following scenarios:

• Patients presenting with nipple discharge, especially if bilateral or milky 1
• Burning or focal pain localized to the subareolar area or nipple 1, 2
• Patients with low testosterone combined with low or low-normal luteinizing hormone levels who develop breast symptoms 1
• Any patient on medications that can elevate prolactin (antipsychotics, metoclopramide, etc.) 1

If prolactin is elevated, repeat the measurement to confirm it is not spurious 1

Persistently elevated prolactin warrants:

• Referral to endocrinology for evaluation of pituitary adenomas (prolactinomas) 1
• Pituitary MRI if testosterone <150 ng/dL with low/normal LH, regardless of prolactin level 1

Estrogen's Role in Nipple Discomfort

Estrogen contributes to nipple discomfort primarily through cyclical hormonal fluctuations:

• Cyclical mastalgia (70% of breast pain cases) is hormonally driven, waxing and waning with the menstrual cycle 4
• Measure serum estradiol in testosterone-deficient patients who present with breast symptoms or nipple tenderness prior to commencing testosterone therapy 1
• Elevated baseline estradiol measurements require endocrinology referral 1
• Men who develop nipple tenderness on testosterone therapy may experience increased estradiol as total testosterone increases, though symptomatic breast complaints are uncommon 1

Testosterone and Hormone Therapy Considerations

In transgender patients receiving gender-affirming hormone therapy:

• Transfeminine patients treated with antiandrogens and estrogens can develop nipple discharge related to hormone-induced hyperprolactinemia 1
• Mammary development from hormone therapy creates functional breast tissue histologically identical to cisgender females, making these patients susceptible to the same hormone-related breast symptoms 1

Critical Pitfalls to Avoid

• Do not dismiss nipple discomfort without measuring prolactin, especially if accompanied by discharge or subareolar burning pain 1, 2
• For smokers with periductal inflammation and burning nipple pain, advise smoking cessation as this is associated with nonpuerperal mastitis 1, 4
• Recognize that hyperprolactinemia may present with mastitis as the first symptom - in one study, 11 of 22 patients with severe hyperprolactinemia had mastitis as their initial presentation 2
• Chronic nipple stimulation from piercings alone does not cause sustained hyperprolactinemia in the absence of infection 5