New discovery lowers prolactin and estrogen while raising T in men

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New discovery lowers prolactin and estrogen while raising T in men

Prolactin is a hormone released by the pituitary gland that contributes to lactation in females, and manboobs in males. 

Not only that, prolactin also contributes to central obesity in BOTH sexes. 

This is thought to occur as a means to “cushion the fetus” during pregnancy, which makes sense in females…

But the reason it also occurs in males is difficult to understand. 

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Regardless, it certainly does happen. Hyperprolactemia leads to both manboobs and visceral adiposity in males, but luckily for us, providence has supplied us with Vitex agnuscastus

This plant has historically been called the “chaste tree,” and studies since the ’80s have consistently reaffirmed this name. 

Because of the reproduction-inducing effects of prolactin in females, it’s understandable that Vitex agnuscastus should be called the “chaste tree.”

In males however, a prolactin “deficiency” doesn’t affect hormone levels or reproductive functions in the slightest. 

Since prolactin in males seems nearly worthless, perhaps a vestige of evolution, then reducing its concentration would appear perfectly safe. 

Both prolactin and its receptor are upregulated by estrogen, which is likely why males often have a smaller amount than premenopausal females. 

Prolactin release is also strongly induced by thyrotropin-releasing hormone, which is depicted below, a fact no doubt responsible for the gynecomastia that accompanies hypothyroidism:

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Another notable compound shown to induce prolactin release is γ-aminobutyric acid (GABA), perhaps explaining why green tea extracts have been shown to elevate it in mice. 

Gamma-aminobutyric acid has bimodal effects on prolactin release depending on the species and route of administration, yet it increases it in humans when given orally. 

Green tea contains threonine, a molecule very similar to GABA that appears to activate its receptors. 

This could be the main reason for green tea’s effect, but it also contains enough fluoride to cause hypothyroidism and consequent TRH release.

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So there’s a few things produced in our bodies shown to release prolactin — e.g. estradiol, TRH, GABA, endorphins — yet only 1 known to universally inhibit it: dopamine.

This is where Vitex agnuscastus comes in. On account of dopamine being the main agent known to inhibit prolactin at the time, the first publication on Vitex‘s effects used lisuride as a positive control.

Lisuride is a D2 receptor agonist similar to bromocriptine. 

In other words, the dopamine pathway was suspected from day 1 in underlying the prolactin-lowering effect of Vitex agnuscastus:

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Although proof of Vitex‘s effects were presented in a 1986 conference, it wasn’t until 1993 that it was published in a journal article. 

The authors first had to cash in on their prolactin-lowering herbal supplement Mastodynon®, greedy as they were.

The prolactin-lowering effect of Vitex agnus-castus is so profitable that it was kept secret for 7 years. 

Because the precise component(s) responsible for Vitex weren’t known back then, whole-plant extracts were used to ascertain its effects. 

Rat pituitary cells were used, and the prolactin released into the media was quantified.

This effect of Vitex extract is graphed below “in reverse,” with increasing concentrations going from right to left.

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I am not exactly sure why they graphed it “in reverse,” or with concentrations decreasing from left to right. Perhaps the journal it was published in had a large Jewish following back then?

Regardless, the effect of Vitex is considerable: the 2 highest concentrations used, 460 and 230 μgml, had reduced prolactin by half. 

This would no doubt translate into less manboobs and lower abdominal fat, something the authors were well aware of.   

“Therefore Agnus castus could be applied to man as alternative treatment of slight hyperprolactinaemia and associated disorders.” ―Sliutz, 1993

They also showed that its inhibition was similar to that of lisuride, thus implying a dopaminergic mechanism for the effect. 

Yet we don’t have to settle for just that because only 1 year later, a team from Germany provided more evidence:

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They first confirmed the results of the prior study, demonstrating that Vitex could inhibit prolactin release from rat pituitary cells. 

They also used thyrotropin-releasing hormone as a technique to augment prolactin release, and examined Vitex‘s ability to antagonize it, which it had. 

Similar to the previous study, they also graphed the Vitex concentrations “in reverse” of the usual convention — e.g., increasing from left to right.

This could imply that this was common practice in Germanic countries at the time, or that Experimental and Clinical Endocrinology was a popular journal in Israel. 

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But what differentiates this study from any published previously is their dopamine binding assay in which 125I-sulpride — a D2 receptor agonist — could be displaced by other dopaminergic agents. 

They showed that Vitex extracts in the milligram per milliliter range could displace 125I-sulpiride binding as effectively as 40-120 μM dopamine. 

This is significant, and seems capable of explaining its effects in vivo.

Since prolactin occupies the bulk of Vitex studies, and the pituitary contains only D2-type dopamine receptors, its effects on the D1-type currently remain unpublished. 

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They also showed that Vitex agnuscastus had no influence on 2 other pituitary products, luteinizing and follicle-stimulating hormone, which further demonstrates its dopamine-specific nature. 

1 year later, the same German group had published its effects in whole living rats, reporting that Vitex extract intravenously could decrease post-stress prolactin release.

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They also reported their data in 56 humans, half given Vitex and the other half a placebo. 

Prolactin decreased by 0.76 ngml in the placebo group, an insignificant amount, but it fell 5.02 ngml in the Vitex group. 

Basal prolactin concentrations weren’t reported, but seeing as it’s generally around 8 ngml in females this would be a significant reduction. 

They didn’t test its effects in males, yet 1 year later, a different group of Germans based in Frankfurt did:

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This was a crossover study using 20 men; initially given a placebo, followed by 3 escalating doses of Vitex extract: 120, 240, and 480 mgd.

They made their own extracts using dried Vitex fruit, but their wording was somewhat ambiguous about the doses, perhaps the translators’ fault. 

They could’ve meant either 120 to 480 milligrams of extract or the amount extracted from 120 to 480 milligrams of dried chasteberry, you decide:

“The medication sequence was determined as follows: placebo, special Agnus castus extract dose A (extract from 120 mg of ‘treatment’ per day), dose B (extract from 240 mg of ‘treatment’ per day), dose C (extract from 480 mg of ‘treatment’ per day).” ―Merz, 1996

I certainly hope they used “120 to 480 milligrams of extract” because Mastodynon® contains 162mg per capsule and 2 capsules are recommended each day. 

If the other possibility were true, it’d probably be too weak to have much affect. 

Yet they did demonstrate a dose-dependent reduction in both basal & TRH-stimulated prolactin release using Vitex, finally confirming it works in human males as well:

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Even though this study was underpowered (n = 20) and used intravenous TRH 4 times in 2 weeks, a potential confounder, the cumulative data of all studies paints a clear picture. 

As a dopaminergic agent, Vitex agnuscastus is very reliable in lowering prolactin. 

So what component(s) in Vitex is responsible for these effects? Is this safe, and is the same thing found in other plants?

The Göttingen study group attempted to determine this back in 1995 without success, but a German PhD dissertation surfaced a few years later which implicated 2 molecules in the benzene fraction: 

Rotundifuran and diacetoxy-13-hydroxy-labda-8,14-diene were shown to be 2 potent dopaminergic agents in Vitex

Perhaps feeling a bit deflated that a graduate student accomplished what they had failed to, the Göttingen study group carried out some binding studies and rushed an article into print:

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They acknowledged the 2 molecules implicated by Berger and discovered 3 more. 

2 of the 3 are apparently novel and specific to Vitex, yet 1 had been isolated previously from Haplopappus parvifolius.

All 5 of these molecules are very similar and are based around a labdane backbone:

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Using a D2-binding assay, he compared each one, finding that the newly discovered compound B-115 was undoubtedly the most potent. 

This was slightly over ⅕ the potency of dopamine itself, pretty good for a fruit that grows in Georgia. 

Compound B-115 has no common or non-prolix IUPAC name, but it’s quite similar to a deacetylated rotundifuran.

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So it might appear as though he found the more significant compound, yet when normalized to the amount actually contained in Vitex it’s about equal. 

In other words: even though compound B-115 is the most potent gram-for-gram, the whole Vitex extract contains enough rotundifuran (P-107) to match its dopaminergic activity. 

So it should be no surprise that neither rotundifuran or B-110, as tested by others, could individually match the potency of the whole hexane extract.

It’s also been shown that Vitex has some opiate receptor-binding substances in the water fraction, which could be significant. 

Although it’s impossible to say from the data whether it activates or blocks opiate receptors, you’d tend to assume the latter considering its effects on prolactin. 

For this reason, the effects of Vitex on prolactin could extend beyond the labdanes found in the hexane fraction. 

“Our results indicate a dopaminergic effect of Vitex agnus-castus extracts and suggest additional pharmacological actions via opioid receptors.” ―Meier, 2000

This is especially true considering that 7 years later, the Göttingen group isolated 2 clerodanes. 

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These clerodanes are very similar to the labdanes, and also have dopaminergic activity. 

Although not quite as potent as B-115 above gram-for-gram, together they contribute more dopaminergic activity than anything else towards the whole Vitex extract:

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They are called “BNO-diterpenes” because they were extracted with nitrosobenzene, a Benzene with a Nitrogen and Oxygen attached. 

So Vitex agnus-castus is certainly a worthwhile thing to consider for lowering prolactin, along with avoiding green tea and taking prothyroid supplements. 

Selenium, vanadium, and iodide are the 3 cofactors needed for maximum thyroid hormone synthesis.

The opiate peptides in wheat have also been shown to increase prolactin, so avoiding this could be a good idea. 

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Matt Cook is editor-in-chief of Daily Medical Discoveries. Matt has been a full time health researcher for 26 years. ABC News interviewed Matt on sexual health issues not long ago. Matt is widely quoted on over 1,000,000 websites. He has over 300,000 daily newsletter readers. Daily Medical Discoveries finds hidden, buried or ignored medical studies through the lens of 100 years of proven science. Matt heads up the editorial team of scientists and health researchers. Each discovery is based upon primary studies from peer reviewed science sources following the Daily Medical Discoveries 7 Step Process to ensure accuracy.


[1] Sliutz, G. "Agnus castus extracts inhibit prolactin secretion of rat pituitary cells." Hormone and metabolic research (1993)


[1] Jarry, H. "In vitro prolactin but not LH and FSH release is inhibited by compounds in extracts of Agnus castus: direct evidence for a dopaminergic principle by the dopamine receptor assay." Experimental and Clinical Endocrinology & Diabetes (1994)


[1] Wuttke, W. "Dopaminergic compounds in Vitex agnus castus." Phytopharmaka in Forschung und klinischer Anwendung. Steinkopff, 1995. 81-91.


[2] Christoffel, V. "Prolactin inhibiting dopaminergic activity of diterpenes from Vitex agnus castus." Phytopharmaka V. Steinkopff, Heidelberg, 1999. 209-214.


[3] Merz, P. "The effects of a special Agnus castus extract on prolactin secretion in healthy male subjects." Experimental and clinical endocrinology & diabetes (1996)


[4] Jarry, Hubertus. "In vitro assays for bioactivity-guided isolation of endocrine active compounds in Vitex agnus-castus." Maturitas (2006)