Oral Contraceptives and Prolactin Levels
Yes, oral contraceptives do increase prolactin levels in women of reproductive age, with a small but statistically significant elevation that occurs within the first few months of use.
Magnitude of Effect
Combined oral contraceptives containing estrogen cause prolactin levels to rise by approximately 15-25% above baseline values. 1 In a prospective longitudinal study of 126 normal premenopausal women, mean prolactin concentration increased from 8.9 ng/ml at baseline to 10.2 ng/ml at 3 months (P < 0.05) and 10.9 ng/ml at 12 months (P < 0.001) in those using oral contraceptives. 1 Women using intrauterine devices showed no change in prolactin levels over the same period, confirming this is a hormonal effect specific to oral contraceptives. 1
Incidence of Hyperprolactinemia
- Approximately 30% of women taking oral contraceptives develop some degree of hyperprolactinemia during treatment. 2
- The incidence of hyperprolactinemia in oral contraceptive users (12%) is more than double that of control subjects (5%). 3
- Importantly, this hyperprolactinemia is often transient and resolves spontaneously in about 50% of affected women, even with continued oral contraceptive use. 3
Dose-Response Relationship
The estrogen component drives the prolactin elevation, though the relationship is not strictly linear:
- 50-microgram estrogen-containing oral contraceptives double basal prolactin levels at 5-8 weeks in women with initial control values below 15 ng/ml. 4 However, this elevation is no longer evident at 6 months of use, suggesting tachyphylaxis. 4
- 35-microgram estrogen-containing oral contraceptives fail to significantly alter prolactin levels at 5-8 weeks in women with control values less than 15 ng/ml. 4
- Neither the dosage of steroids nor the duration of therapy consistently correlates with the presence or degree of hyperprolactinemia across all studies. 2
Individual Susceptibility
Some women appear more sensitive to the prolactin-stimulating effects of exogenous estrogen. 3 Estrogen provocation studies suggest that women who develop hyperprolactinemia while taking oral contraceptives may be at greater risk of developing pill-related menstrual aberrations. 3 This individual variation explains why not all women experience prolactin elevation despite similar hormonal exposure.
Effect on Macroprolactin
In women with pre-existing macroprolactinemia, oral contraceptives containing ethinyl estradiol and levonorgestrel exhibit a stimulatory effect on macroprolactin production. 5 After 16 weeks of treatment, both pre-polyethylene glycol serum prolactin levels and macroprolactin levels increased slightly, with the magnitude of effect correlating with baseline values. 5
Clinical Context
The prolactin elevations induced by oral contraceptives, while statistically significant, are generally modest and rarely cause clinical symptoms in otherwise healthy women. 1, 4 The relationship between prolactin and oral contraceptives is relevant in specific contexts, such as lactation management in women with hereditary angioedema, where increased prolactin levels have been associated with increased frequency of abdominal attacks. 6
Common Pitfalls to Avoid
- Do not assume all women will experience the same degree of prolactin elevation—individual susceptibility varies significantly. 3, 4
- Do not interpret a single elevated prolactin level in an oral contraceptive user as pathologic—multiple blood sampling is more accurate, and transient elevations are common. 3
- Do not overlook that prolactin elevations may diminish over time despite continued oral contraceptive use, particularly with higher-dose formulations. 4