Mechanism of Prolactin-Induced Amenorrhea
Prolactin inhibits the release of gonadotropin-releasing hormone (GnRH), which is the primary mechanism by which hyperprolactinemia causes amenorrhea. 1, 2
The Correct Mechanism
Prolactin suppresses pulsatile GnRH secretion from the hypothalamus, which subsequently reduces LH pulse frequency and disrupts the normal hormonal cascade required for ovulation. 2 This represents a direct effect on the hypothalamic-pituitary-gonadal axis at the level of the hypothalamus. 3
Evidence Supporting GnRH Inhibition
Experimental studies demonstrate that hyperprolactinemia decreases LH pulse frequency from 8.7 to 6.0 pulses per 12 hours, confirming suppression of GnRH pulsatility. 2
The mechanism involves prolactin increasing tuberoinfundibular dopamine turnover, which suppresses hypothalamic GnRH secretion. 2
This GnRH suppression results in disturbed secretion of pituitary gonadotropins with low LH levels, characteristic of hypothalamic amenorrhea. 3
Hyperprolactinemia accounts for approximately 20% of secondary amenorrhea cases through this mechanism. 1, 4
Why the Other Options Are Incorrect
Prolactin Does NOT Increase FSH Release
The question option suggesting "prolactin increases the release of FSH leading to no ovulation" is physiologically incorrect. 2
In fact, hyperprolactinemia is associated with low or normal gonadotropin levels, not elevated FSH. 5, 6
Studies show that patients with hyperprolactinemic amenorrhea release only minimal amounts of LH and FSH, demonstrating impaired gonadotropin reserve. 6
Prolactin Does NOT Stimulate Excessive Estrogen
Prolactin actually inhibits estrogen synthesis in the ovary by interfering with FSH action on granulosa cells. 7
Hyperprolactinemic amenorrhea is characterized by estrogen deficiency, not excess, which leads to complications like osteoporosis. 8
The hypoestrogenic state is a direct consequence of impaired follicular development due to disrupted GnRH/gonadotropin secretion. 8
Progesterone Decrease Is Secondary, Not Primary
While progesterone production is indeed decreased in hyperprolactinemic amenorrhea, this is a secondary consequence of anovulation, not the primary mechanism. 3
The fundamental problem is the suppression of GnRH pulsatility, which prevents normal follicular development and ovulation, thereby eliminating the corpus luteum that would produce progesterone. 2
Clinical Implications
Functional hyperprolactinemia causes amenorrhea, oligomenorrhea, subfertility, galactorrhea, and hirsutism through this GnRH suppression mechanism. 3
Treatment with dopamine agonists (such as bromocriptine) restores normal GnRH pulsatility by reducing prolactin levels, which subsequently restores follicular growth and ovulation. 7, 8
The degree of GnRH disruption determines clinical severity—mild suppression may cause oligomenorrhea, while severe suppression results in complete amenorrhea. 2
Important Diagnostic Consideration
- Not all elevated prolactin requires treatment—macroprolactinemia (biologically inactive "big big molecule") can cause falsely elevated prolactin levels in normally ovulating women and does not require intervention. 8