Abstract
Background/Objective
Elevated prolactin levels are associated with galactorrhea, menstrual irregularities, or infertility. While nicotine is known to affect prolactin secretion via dopaminergic pathways, noncombustible nicotine products such as pouches are rarely considered as contributing factors. The objective of this report is to describe a patient with hyperprolactinemia associated with nicotine pouch use, highlighting a potentially overlooked etiology.
Case Report
A 21-year-old woman with a history of attention deficit hyperactivity disorder and bipolar disorder presented with infertility after 12 months of trying. She had discontinued oral contraceptives and risperidone 1 year prior, as she wanted to start her family, with improvement in breast engorgement and galactorrhea over the last 12 months, she reported regular menstrual cycles. She had quit smoking 2 to 3 weeks prior to having her prolactin levels checked and had started using 10-12 nicotine pouches daily (6 mg each) to help with nicotine cravings. Initial labs showed a prolactin level of 312 ng/mL (reference: 5.2–26.5 ng/mL), thyroid-stimulating hormone 1.18 uIU/mL (0.40–4.00 uIU/mL), and β-human chorionic gonadotropin <2 mIU/mL (reference: <5 mIU/mL).She discontinued nicotine pouches immediately after seeing high prolactin levels, and prolactin levels normalized 2 and 3 days later (13.4 ng/mL, then 8.8 ng/mL, respectively).
Discussion
Nicotine may increase prolactin by inhibiting dopamine’s regulatory effects. While this is documented in smokers, its impact via nicotine pouches is less well studied.
Conclusion
This case highlights nicotine pouch use as a possible cause of hyperprolactinemia. Clinicians should consider alternative nicotine products when evaluating patients with unexplained hyperprolactinemia.
Key words: hyperprolactinemia, nicotine pouches, prolactin, noncombustible nicotine products
Highlights
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Nicotine’s risks are established; its endocrine effects are less acknowledged
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Nicotine has been shown to affect prolactin secretion in a dose-dependent manner
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The rise of tobacco-free nicotine use calls for a study of its hormonal health effects
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The link between nicotine and hyperprolactinemia underscores the need for screening
Clinical Relevance
Prolactin elevation more than 5-fold the upper level of normal is considered significant. In this, patient greater than 25-fold elevation was likely caused by using nicotine pouches. The use of nicotine products (pouches, vaping, E-cigarettes) should be part of a detailed history elicited in patients with hyperprolactinemia.
Introduction
Nicotine is a widely used psychoactive substance that acts on nicotinic acetylcholine receptors in both the central and peripheral nervous systems. While its cardiovascular and pulmonary risks are well-established, nicotine also has significant, though less frequently discussed, endocrine effects. These include hypothalamic-pituitary-adrenal axis stimulation, elevated cortisol levels, increased insulin resistance, and associations with infertility and osteoporosis.1
Nicotine pouches are small microfiber pouches that contain a powder made of nicotine and flavoring agents. These pouches are referred to as nontobacco- nicotine; however, there is little chemical difference between tobacco derived nicotine and synthetic nicotine. This case report describes a young woman who developed marked hyperprolactinemia associated with the use of high-dose nicotine pouches, which resolved rapidly upon cessation, suggesting a potentially underrecognized link between this delivery system and prolactin elevation.
Case Report
A 21-year-old woman with a medical history of attention deficit hyperactivity disorder, bipolar disorder, asthma, environmental allergies, and premature adrenarche presented to gynecology for infertility evaluation. She had discontinued oral contraceptives and risperidone 1 year prior and reported regular menstrual cycles (every 30 days), intermittent breast engorgement, and mild and intermittent galactorrhea which was progressively improving after stopping risperidone.
Initial laboratory results revealed a high prolactin level of 312 ng/mL (reference range: 5.2–26.5 ng/mL), TSH: 1.18 uIU/mL (reference range: 0.40–4.00 uIU/mL) and beta human chorionic gonadotrophic hormone: <2 mIU/mL (reference range: <5 mIU/mL). She denied headaches or visual disturbances. Endocrinology was consulted and repeat prolactin levels 2 and 3 days after stopping the use of nicotine pouches were 13.4 ng/mL and 8.8 ng/mL, respectively. See Figure 1 and Table 1 for prolactin trends before and after nicotine cessation.
Fig. 1.
Prolactin levels before and after nicotine cessation.
Table 1.
Initial Endocrine Laboratory Evaluation
| Time point | TSH, mIU/mL | β-hCG, mIU/mL | Reference ranges |
|---|---|---|---|
| Before nicotine cessation | 1.18 | <2 | TSH: 0.40–4.00 μIU/mL β-hCG: <5 mIU/mL (nonpregnant adult) |
Abbreviations: β-hCG = beta-human chorionic gonadotropin; μIU/mL = micro–international units per milliliter; mIU/mL = milli–international units per milliliter; TSH = thyroid-stimulating hormone.
Her medication history included risperidone, which had been discontinued over 1 year prior, and she denied any current use of medications known to elevate prolactin.
Importantly, the patient had recently switched from cigarette smoking to using nicotine pouches—consuming 10–12 pouches daily, each containing 6 mg of nicotine (60–72 mg/d total) Figure 2. She discontinued use immediately upon learning of her elevated prolactin. No pituitary imaging was pursued given the rapid normalization of levels and symptom resolution.
Fig. 2.
Nicotine pouch. Each pouch contains 20 sugar-free pouches.
Discussion
This case highlights symptomatic hyperprolactinemia likely induced by high-dose nicotine pouches, a novel and underrecognized cause in endocrine evaluation. Although venipuncture induced stress can elevate prolactin, the degree of hyperprolactinemia seen in this case is unlikely to result from stress alone. Additionally, the patient’s symptoms of intermittent breast engorgement and galactorrhea argue against the acute stress-induced prolactin elevation. The patient’s initial prolactin level (312 ng/mL) was markedly elevated and raised suspicion for a prolactin-secreting adenoma. However, the absence of visual symptoms and the normalization of prolactin within days without treatment strongly suggest a reversible, non-neoplastic etiology. Patients with persistent hyperprolactinemia, even in the presence of a medication that is known to cause hyperprolactinemia, should get central imaging to rule out the presence of macroadenoma. However, in this patient, the hyperprolactinemia was not persistent and returned to normal after stopping nicotine pouches. Incidentalomas are quite common, present in about (7%) of the population. Given lack of symptoms and low concern for pituitary tumors, an informed decision was made not to get MRI of the Sella in this case.
Acute and subacute nicotine exposure has been demonstrated to increase prolactin secretion. Studies on both humans and animals reveal that nicotine elevates serum prolactin levels in a dose-dependent manner. Benowitz et al2 noted heightened prolactin levels in chronic male smokers following the use of high-nicotine (2.0 mg) cigarettes, while low-dose (0.2 mg) cigarettes did not trigger this increase. Likewise, Tsuda et al found that prolactin levels rose by about 1 ng/mL for every 10 ng/mL increase in venous plasma nicotine.3 In rodent studies, intravenous nicotine led to increased prolactin levels, an effect that mecamylamine, a nicotinic receptor antagonist, could reverse.4 In contrast to acute nicotine exposure, chronic nicotine stimulation can result in suppression of prolactin levels as evidenced by lower prolactin levels in chronic smokers. This is likely due to receptor desensitization from chronic effects of the nicotine metabolite cotinine.5
Nicotine pouch products contain nicotine salts and filling materials. They are tobacco-free and are placed between the upper lip and gums for a period during which a majority of nicotine is absorbed through the buccal mucosa, and a smaller percentage of nicotine is mixed in saliva and absorbed systemically. Though considered safer from a pulmonary standpoint, they may still exert systemic effects, including hormone levels.6
Nicotine stimulates nicotinic acetylcholine receptors, modulating dopaminergic tone in the hypothalamus. Because dopamine tonically inhibits prolactin release, nicotine can reduce this inhibition, resulting in elevated prolactin.2,4 Studies in rodents have also demonstrated that nicotine-induced prolactin elevation is attenuated by naltrexone, indicating a role for endogenous opioid signaling.7,8
Unlike other stimulants such as cocaine or methylphenidate, which increase dopamine and decrease prolactin, nicotine exerts a unique endocrine effect.9
Although nicotine pouches have not been approved by the U.S. Food and Drug Administration for smoking cessation, their use is increasing. As these products become more prevalent, clinicians must recognize their systemic effects, including on prolactin levels. Importantly, current guidelines10 for hyperprolactinemia do not routinely recommend screening for nicotine product use, a gap this case underscores.
Conclusion
The case illustrates that even noncombustible nicotine products, such as pouches can significantly disrupt prolactin regulation. It emphasizes the need to include detailed histories of nicotine use, especially newer forms like pouches, in the diagnostic workup for hyperprolactinemia.
Statement of Patient Consent
Patient consent was obtained for this case report.
Disclosure
The authors have no conflicts of interest to disclose.
References
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