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Prolactin triggers male refractory interval, signifies examine

When you type in a search engine – “Why do men have to wait before having sex again?” – You will encounter prolactin very quickly. This tiny hormone is believed to be involved in hundreds of physiological processes in the body. Among them is the male refractory period after ejaculation. This period starts when a man ejaculates and ends when he regains his sexual skills.

If you do a little more research, you will find that this theory even led to the development of so-called “treatments”. These promise to shorten a person’s refractory period by lowering their body’s prolactin levels.

Well, here is some bad news for anyone who has bought goods like this. A new study on mice by scientists at the Champalimaud Center for Unknowns in Portugal shows that prolactin may not be the culprit after all. These results were published today (January 4th) in the journal Communications Biology.


Ironically, the research project that ultimately disproved the theory never aimed at that.

“When we started working on this project, we actually went out to explore the theory,” recalls Susana Lima, the lead researcher who led the study. “Our aim was to investigate more closely the biological mechanisms by which prolactin could produce the refractory period.”

What is the basis of the theory? According to Lima, it was created through multiple lines of evidence.

For one, some studies have shown that prolactin is released around the time of ejaculation in humans and rats. And since the refractory period begins immediately after ejaculation, prolactin seemed a good candidate.

Chronically unusually high levels of prolactin are also associated with decreased sex drive, anorgasmia and ejaculatory dysfunction. Finally, treatment with drugs that inhibit prolactin release in chronically high prolactin situations will reverse sexual dysfunction.

“These different results all point to a central role for prolactin in suppressing male sexual behavior,” says Lima. “However, a direct link between prolactin and post-ejaculatory refractory periods in men has never been directly established. Yet this theory is so widespread that it is now appearing in both textbooks and the popular press.”

Why not prolactin?

How did the team find out the theory was wrong?

To investigate the role of prolactin in the male refractory period, Lima and her team performed a series of experiments on mice.

“We chose mice as our model animal because the sequence of sexual behavior in mice is very similar to that in humans,” explains Susana Valente, the study’s lead author. “We can also use mice to test different strains that have different sexual performance, which gives us richer data. In this case, we used two different strains, one with a short refractory period and one with a long, multi-day period.”

The team began by checking whether prolactin levels also rise during sexual activity in male mice. “We measured the values ​​in the various stages of sexual behavior using blood samples. And they actually increased significantly during sexual interaction,” says Valente

After confirming this aspect, the researchers examined the relationship between prolactin and the length of the animals’ refractory period.

Our first manipulation was to artificially increase the level of prolactin before the animals were sexually aroused. We took special care that the artificial values ​​correspond to those that we measured during natural sexual behavior. If prolactin was indeed the cause of the refractory period, the animals’ sexual activity should have decreased. “

Susana Valente, first author of the study, Champalimaud Center for the Unknown

To their surprise, this manipulation did not affect the sexual behavior of the mice. “Despite the rise in prolactin levels, both strains of mice behave normally sexually,” she recalls.

Next, the researchers turned to see if blocking prolactin would have the opposite effect on refractory period. In other words, if animals were more sexually active without prolactin. Again the answer was “no”.

“If prolactin was actually necessary for the refectory period, men without prolactin should have regained sexual activity faster than control persons after ejaculation,” stresses Valente. “But they didn’t.”

Back to the drawing board

Together, the results of Valente and Lima provide strong counter-evidence for the theory that prolactin triggers the refractory period in men. Still, prolactin is undoubtedly a part of male sexual behavior. What could his role be?

“There are many options,” says Lima. “For example, there are studies that suggest a role of prolactin in establishing parental behavior. It is also important to note that the prolactin dynamics in male mice and men are very different. In mice, prolactin levels rise during mating. In men, prolactin appears to be released only at the time of ejaculation and only when ejaculation is reached. Hence, there may be some differences in its role between species. “

What’s the reason men have to wait before the second round?

“Our results show that prolactin is very unlikely to be the cause,” says Lima. “Now we can go ahead and see what is really going on,” she concludes.


Champalimaud Center for the Unknown

Journal reference:

Valente, S. et al. (2021) No evidence of prolactin involvement in the post-ejaculatory refractory period. Communication biology. doi.org/10.1038/s42003-020-01570-4.

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