Malaria compound to treat polycystic ovary syndrome

Artemisinins, plant-based antimalarials, may serve as a treatment for polycystic ovary syndrome - which affects millions of women worldwide and can lead to infertility - according to a new study published in Science. The compounds suppressed ovarian androgen production in rodents, as well as in a small cohort of 19 human patients for 12 weeks, leading to more regular menstrual cycles without side effects. 

13/06/2024 - 20:00 CEST
 
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Cristina Carrasco - malaria ovarios EN

Cristina Carrasco

Substitute lecturer and researcher at the Department of Physiology, Faculty of Medicine and Health Sciences of the University of Extremadura

Science Media Centre Spain

This research demonstrates the effectiveness of the therapeutic application of compounds derived from the Artemisia plant, known as artemisinins, in polycystic ovary syndrome (PCOS). This is one of the most common endocrine disorders in women of reproductive age, which impairs their quality of life and even their reproductive capacity. Generally, it is characterized by an excess of male hormones or androgens, which are primarily responsible for some of the typical symptoms, such as ovulation disturbances, numerous cysts in the ovaries, and, in some cases, metabolic problems. Currently, available therapeutic options are scarce, limited to alleviating symptoms, and have undesirable side effects. Hence the importance of finding new effective and safe treatments that directly address androgen overproduction. 

In this interesting study published by the journal Science, the research team explores in depth the physiological effect of artemisinins and their derivatives, not only in isolated cells and animal models of this syndrome but also in patients. Through successive meticulously conducted experiments, they precisely identify the therapeutic target of these compounds, ruling out any effect on the levels of other hormones or proteins involved in the process, or on the androgen-producing cells themselves. Thus, the results show that artemisinins are capable of reducing the levels of the enzyme responsible for the first step in androgen synthesis, called CYP11A1. Specifically, these plant derivatives act as a 'molecular glue' between this enzyme and the LONP1 protein, located in the mitochondria and responsible for its degradation, ultimately inhibiting ovarian androgen overproduction, such as testosterone. Following these molecular findings, the researchers conducted a pilot study in 19 women with polycystic ovary syndrome that confirmed the effectiveness of oral artemisinin administration for 12 weeks, reducing serum androgen levels, improving the morphology of polycystic ovaries, and restoring menstrual cycles in 63% of the patients. 

It is worth noting that this would be the first study on the potential therapeutic application of artemisinins, widely recognized as a treatment for malaria, in polycystic ovary syndrome. However, as with all research, there are certain limitations that could influence the results obtained. In this regard, the authors point out that it is necessary to develop animal models that accurately reproduce the pathology in women to extrapolate the experimental evidence and determine both the optimal dose and long-term effects. 

In summary, this brilliant research reinforces the promising future in the research, development, and clinical application of plant extracts in female reproductive disorders, which experimentally show greater efficacy and safety than conventional treatments. In this case, we would also be talking about the repositioning of an antimalarial drug for use in women's health. Undoubtedly, more scientific studies like this one are needed to expand our knowledge about the pathophysiology of highly prevalent diseases among women, as an essential step for successful treatment in all aspects. 

The author has declared they have no conflicts of interest
EN

Cornelia Jaursch-Hancke - malaria ovario poliquístico EN

Cornelia Jaursch-Hancke

Head of the Department of Diabetology and Endocrinology, DKD Helios Clinic Wiesbaden

Science Media Center Germany

In addition to oral contraceptives, we currently have a highly effective treatment for polycystic ovary syndrome (PCOS): metformin. This is a drug that we have been using for over 30 years, which offers a high level of safety and can only cause minor short-term side effects in the gastrointestinal tract, which can usually be avoided with an adequate dosage regimen. In addition, many alternative treatment options are being discussed, such as inositol, resveratol, monk’s pepper, coenzyme Q10, ginseng, curcumin and others. There are similar studies that have shown effects for these, but they did not show sufficient effect in placebo-controlled follow-up studies. Only inositol is mentioned in the international guidelines: as ‘could be considered’. Some even have negative effects. We are also currently working on a first detailed national guideline for Germany, which will be published soon.

The herbal active ingredient artemisinin from mugwort is also used for other indications. These include artemisinin-based active ingredients against malaria parasites, although the WHO is already warning of resistance here. We do not yet know the exact effects of artemisinin on the human organism. The study by Liu et al. only examines how artemisinin effects the enzymes that are involved in PCOS. But they did not investigate what other effects the drug can cause. These could also be undesirable side effects.” “The study is methodologically well done. It provides good evidence of the mechanism of action on testosterone production in rodents. What it does not show, are positive effects on the metabolism, there are none at all. As already mentioned, there is a lack in the investigation of the effects in the rest of the body. Overall there could even be a harmful effect. The observational study on 19 patients who were only treated for 12 weeks is not sufficient.

 What we need is a randomized controlled trial to prove an effect in patients that goes beyond the placebo effect. Then we could look at the results again. Based on my experience with studies on other drug candidates, I don’t see any prospects for artemisinin at the moment. Resveratol, for example, initially showed similar effects on testosterone production, but the results from randomized controlled trials could not show any significant effects.

The author has declared they have no conflicts of interest
EN
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Artemisinins ameliorate polycystic ovarian syndrome by mediating LONP1-CYP11A1 interaction
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Yang Liu et al.

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