Can hyperprolactinemia cause low testosterone in women?

The hormonal disruption caused by hyperprolactinemia significantly impacts the female reproductive axis, extending beyond the well-known effects on estrogen to influence total androgen production.

Clinical and effectiveness evidence

Hyperprolactinemia is a primary driver of hypogonadotropic hypogonadism. In this state, elevated prolactin levels create a functional deficiency in the hormones that regulate the ovaries.

• Gonadotropin suppression: Extensive research confirms that high prolactin levels disrupt the pulsatile release of Gonadotropin-Releasing Hormone (GnRH). This suppression leads to a subsequent decline in the secretion of Luteinizing Hormone (LH) and Follicle-Stimulating Hormone (FSH) from the pituitary.
• Impact on androgens: In women, approximately 50% of circulating testosterone is derived from the ovaries (either through direct secretion or the peripheral conversion of ovarian androstenedione). Because LH is the primary stimulus for the ovarian theca cells to produce these androgens, the reduction in LH pulses logically results in decreased ovarian testosterone production.
• Clinical presentation: While clinical studies frequently focus on the resulting estrogen deficiency (leading to amenorrhea or bone density loss), the pathway for testosterone reduction is identical. However, some evidence suggests a complex interaction where prolactin may occasionally increase adrenal androgen precursors like DHEA-S, though this rarely compensates for the loss of ovarian output.

Mechanistic explanations

The suppression occurs through a sophisticated neuroendocrine feedback loop:

• Kisspeptin inhibition: Prolactin acts directly on the KNDy (Kisspeptin/Neurokinin B/Dynorphin) neurons in the arcuate nucleus of the hypothalamus. It binds to prolactin receptors (Prlrs) on these neurons, directly inhibiting the expression of kisspeptin. Since kisspeptin is the essential "master switch" for GnRH, its absence halts the entire downstream hormonal cascade.
• Direct ovarian interference: Beyond the brain, prolactin receptors are present on ovarian cells. High levels of prolactin can directly interfere with LH-stimulated androgen synthesis in theca cells and downregulate aromatase (CYP19A1) activity in granulosa cells.
• Dopaminergic activity: Prolactin increases the activity of tuberoinfundibular dopaminergic (TIDA) neurons. While this is a feedback mechanism to inhibit further prolactin release, the increased dopamine can further suppress GnRH pulsatility via D2 receptors.

Bottom line

Hyperprolactinemia is a recognized cause of low testosterone in women. It works by suppressing the hypothalamic kisspeptin-GnRH axis, which removes the LH stimulation necessary for ovarian theca cells to produce testosterone and its precursors.