The Prolactin can be elevated from hCG or testosterone. It is marginally elevated and might even be wnl on re-testing. It might be worthwhile to check E2. [Interestingly, there is a E2-Hepcidin connection that might explain the Ferritin results.]
Evidence for the causal relationship between testosterone replacement and a rise in PRL was suggested by the observation that PRL levels declined when testosterone was temporarily discontinued and rose again with its readministration.
It is postulated that the rise in PRL was a result of the aromatization of testosterone to estradiol, which in turn stimulated PRL synthesis and release. An accumulating body of evidence suggests that estrogen plays an integral role in the pathogenesis and progression of lactotroph tumors. Specifically, estrogen exerts a stimulatory effect upon PRL secretion by disrupting the inhibitory influence of dopamine; chronic exposure to estrogen functionally uncouples the anterior pituitary D2 receptor from its G protein-coupled receptor.
Estradiol in vitro stimulates PRL gene transcription and prevents the ability of dopamine agonists to inhibit PRL synthesis and secretion. In vivo, large doses of estrogens have induced prolactinomas in rats and may induce them in humans as well.
Sodi R, Fikri R, Diver M, Ranganath L, Vora J. Testosterone replacement-induced hyperprolactinaemia: case report and review of the literature. Ann Clin Biochem 2005;42(Pt 2):153-9. Testosterone replacement-induced hyperprolactinaemia: case report and review of the literature
Half of all men with prolactin (PRL)-producing macroadenomas present with hypogonadism, decreased libido and impotence, and therefore require testosterone replacement. However, very little is known about the effect of testosterone on prolactinomas. We report a case of an 18-year-old obese man who presented with hypogonadism and hyperprolactinaemia and underwent a transphenoidal hypophysectomy after a computer tomography scan showed the presence of a suprasellar macroadenoma. On separate occasions, we documented a rise in PRL when testosterone replacement was started and a fall in PRL when testosterone replacement was stopped (r = 0.6090, P = 0.0095). Furthermore, imaging studies suggested the possibility of tumour re-growth after testosterone therapy. We hypothesize that the exogenous testosterone was aromatized to oestradiol, which stimulated the release of PRL by the anterior pituitary. This was supported by the increase in oestradiol levels after testosterone replacement, although statistical significance was not achieved due to the availability of only a few data points. This case highlights the need to be aware of testosterone-replacement-induced hyperprolactinaemia, an under-recognized complication of androgen replacement in this setting. The use of aromatase inhibitors together with testosterone-replacement therapy or the use of non-aromatizable androgens might be indicated in such patients. Taken together, this report and previous studies show that dopamine agonists apparently do not suppress the hyperprolactinaemia induced by testosterone replacement.
Gillam MP, Middler S, Freed DJ, Molitch ME. The Novel Use of Very High Doses of Cabergoline and a Combination of Testosterone and an Aromatase Inhibitor in the Treatment of a Giant Prolactinoma. J Clin Endocrinol Metab 2002;87(10):4447-51. http://jcem.endojournals.org/cgi/content/full/87/10/4447 (The Novel Use of Very High Doses of Cabergoline and a Combination of Testosterone and an Aromatase Inhibitor in the Treatment of a Giant Prolactinoma)
Most prolactinomas respond rapidly to low doses of dopamine agonists. Occasionally, stepwise increases in doses of these agents are needed to achieve gradual prolactin (PRL) reductions. Approximately 50% of treated men remain hypogonadal, yet testosterone replacement may stimulate hyperprolactinemia. A 34-yr-old male with a pituitary macroadenoma was found to have a PRL level of 10,362 {micro}g/liter and testosterone level of 3.5 nmol/liter. Eleven months of dopamine agonist therapy at standard doses lowered PRL levels to 299 {micro}g/liter. Subsequent stepwise increases in cabergoline (3 mg daily) further lowered PRL levels to 71 {micro}g/liter, but hypogonadism persisted. Initiation of testosterone replacement resulted in a rise and discontinuation in a fall of PRL levels. Aromatization of exogenous testosterone to estradiol and subsequent estrogen-stimulated PRL release was suspected. Concomitant use of cabergoline with the aromatase inhibitor anastrozole after resuming testosterone replacement resulted in the maintenance of testosterone levels and restoration of normal sexual function, without increasing PRL. Ultimately, further reduction in PRL on this therapy permitted endogenous testosterone production. Thus, novel pharmacological maneuvers may permit successful medical treatment of some patients with invasive macroprolactinomas.
Nicoletti I, Filipponi P, Fedeli L, Ambrosi F, Gregorini G, Santeusanio F. Testosterone-induced hyperprolactinaemia in a patient with a disturbance of hypothalamo-pituitary regulation. Acta Endocrinol (Copenh) 1984;105(2):167-72. Testosterone-induced hyperprolactinaemia in a patient with a disturbance of hypothalamo-pituitary regulation
A case of a patient with hypopituitarism due to a disturbance of hypothalamo-pituitary regulation is presented, who developed high-grade hyperprolactinaemia after the initiation of substitutive therapy with testosterone esthers. The increase in serum Prl was strictly related to testosterone aromatization to oestradiol, since anti-oestrogen compounds were effective in reducing (clomiphene) or abolishing (tamoxifen) the enhanced Prl secretion. The oestrogen effect in raising Prl release was not attributable to a reduction in the dopamine inhibition of Prl-secreting cells, as the dopamine-antagonist domperidone failed to increase Prl serum levels in the same patient. This suggests that, in man, the oestrogen effect in enhancing Prl release is mainly enacted directly on the pituitary lactotrophs rather than exerted through a reduction in the hypothalamic dopamine activity.
Prior JC, Cox TA, Fairholm D, Kostashuk E, Nugent R. Testosterone-related exacerbation of a prolactin-producing macroadenoma: possible role for estrogen. J Clin Endocrinol Metab 1987;64(2):391-4. http://jcem.endojournals.org/content/64/2/391.abstract (Testosterone-Related Exacerbation of a Prolactin-Producing Macroadenoma: Possible Role for Estrogen)
Men with PRL-producing macroadenomas often present with hypogonadism and impotence. This report documents exacerbation of a PRL-secreting tumor after two separate 200-mg testosterone enanthate (T) injections despite continued bromocriptine (BRC) therapy. A 37-yr-old man with a 60-mm invasive tumor and a serum PRL level of 13,969 +/- 332 ng/ml (mean +/- SD) responded to BRC therapy with rapid disappearance of visual field defect, headache, and facial pain as well as decrease in serum PRL to 5,103 +/- 1,446 ng/ml. T injection was followed by severe headache, facial pain, and increase in PRL to 13,471 ng/ml. Visual field deterioration and increased tumor size (height, 40-43 mm) by computed tomography were documented. A relationship between T injection and exacerbation of the prolactinoma was not recognized until after a second T injection 3 months later. After that therapy, baseline PRL increased from 6,900 to 12,995 ng/ml. The hypothesis that T was aromatized to estradiol, directly stimulating lactotrophs, was supported by an increase in serum estradiol from 24 to 51 pg/ml after the second T injection. Although T treatment is accepted as appropriate therapy for hypogonadism in men with prolactinomas, it may not only interfere with the response of the tumor to BRC therapy, but even stimulate tumor growth and secretion.
