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Review Article
2023
:2;
11
doi:
10.25259/MEDINDIA_20_2023

Need to address the root cause of Polycystic ovary syndrome (PCOS)

Department of Medicine, Institute of Medical Sciences and SUM Hospital, Bhubaneswar, Odisha, India
Department of Medicine, Kasturba Medical College, Mangalore, Karnataka, India
Corresponding author: Jonnalagadda Vihari, PG Resident, Department of General Medicine, Institute of Medical Sciences & SUM Hospital, Bhubaneswar, Odisha, India. viharijtk5@gmail.com
Licence
This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-Share Alike 4.0 License, which allows others to remix, transform, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms.

How to cite this article: Vihari J, Sriteja N, Sahu S, Das C, Dalai SP, Tripathy D, et al. Need to address the root cause of Polycystic ovary syndrome (PCOS). Med India 2023;2:11.

Abstract

I was suddenly startled when I dug into polycystic ovary syndrome pathophysiology. Follicular arrest, a condition that has everything frozen at that pre-ovulatory phase, is the cause of the situation. Millions of dollars are spent yearly on infertility treatments when lifestyle changes may address the problem. This article demonstrates how altering the diet will considerably enhance it. This article allows us to explore novel concepts not part of conventional medical practice.

Keywords

Polycystic ovary syndrome
Follicular arrest
Pre-ovulatory phase
Infertility
Diet

INTRODUCTION

Anovulation is one of the three primary polycystic ovary syndrome (PCOS) criteria. Obesity and ovulation are correlated.[1] The likelihood of ovulation decreases with increasing weight. Even while infertility is not inherently harmful, it puts the person at high risk because it is a significant component of PCOS. Obesity and PCOS are closely associated.[2] We can observe that the prevalence of PCOS is rising as we go from being underweight to being fat [Figure 1]. The same happens with Type-2 diabetes [Figure 2], as there is more insulin resistance, and impaired glucose tolerance, and diabetes prevalence increases with body mass index.[3] Hyperandrogenemia is another crucial criterion. In essence, they have too much testosterone, which is what necessarily leads to masculinizing characteristics such as acne, body and facial hair, and male pattern baldness.

Figure 1:: Prevalence of diagnosed (black) and undiagnosed polycystic ovary syndrome according to NIH criteria (gray) in adolescents aged 15–19 years of age.[2]
Figure 2:: Prevalence of glucose intolerance by body mass index (BMI) in a US.[3] US: United States, PCOS: Polycystic ovary syndrome.

The yearly cost of treating a condition like PCOS is estimated to be $4,370 million [Figure 3],[4] which is a significant financial burden. Millions of dollars are spent yearly on infertility treatments when lifestyle changes may address the problem.

Figure 3:: The overall healthcare-related economic burden of polycystic ovary syndrome patients during their reproductive years in 2004.[4] US: United States, AUB: Abnormal Uterine Bleeding, DM: Diabetes Mellitus.

DISCUSSION

Why does too much testosterone usually occur? As we see in the pathophysiology, testosterone (the principal androgen in the body) is generated by the adrenal gland and the ovaries. The ovary is where the excess testosterone that some people produce comes from. It is an ovarian issue rather than an adrenal issue. The liver produces low sex hormone binding globulin (SHBG), a protein that binds to testosterone and is another element causing hyperandrogenemia. Usually, testosterone is linked to this SHBG and does not circulate freely in the blood very much. The level of free testosterone increases when this SHBG is insufficient. Imagine if we are at a cricket stadium; everyone leaves the stadium once the game is over and wants to take a cab to their homes. If there are not enough cabs available, everyone will mill around. The testosterone should also be attached to this binding globulin in this situation. The testosterone begins to swirl about if there is not enough globulin. Moreover, it is the reason why acne and other problems happen. Insulin is the reason for having too much testosterone [Figure 4]. Studies have shown that testosterone levels increase directly to insulin levels.[5] Moreover, there is an impact on the liver as well; higher insulin levels lower the level of this SHBG.

Figure 4:: Mean testosterone levels during the sequential euglycemic clamp.[5]

High insulin → hyperandrogenemia, low SHBG → masculinizing features

Polycystic ovaries are the second key indicator of polycystic ovarian syndrome. A normal ovary can be seen on the left in the image, and all the cysts can be seen on the right [Figure 5]. Why are these cysts growing? Usually, the ovary forms the egg which gets discharged after a typical menstrual cycle. However, we can see that the polycystic ovary is not getting ovulated [Figure 6]. They will not become pregnant since they are not ovulating. Follicular arrest, a condition that has everything frozen at that pre-ovulatory phase, is the cause of the situation.

Figure 5:: Polycystic ovary when compared to normal ovary.
Figure 6:: Polycystic ovary not got ovulated.

The typical development is shown in [Figure 7], where a preovulatory follicle follows a growing one after a hormone rise leutinizing hormone (LH). If we glance at Section B, there is too much insulin there. Under the influence of excessive insulin, these follicles turned too sensitive to the hormone.[6] Therefore, they have already begun to grow before the LH surge, and we are now witnessing the wrath of the follicles. In other words, they are freezing at a level of 8 mm before they reach the 10–15 cm stage when they are big enough to ovulate.

Figure 7:: (a and b) Proposed mechanism of anovulation in women with polycystic ovary syndrome.[6] LH: luteinizing hormone.

Moreover, for this reason, we have a lot of follicles that are locked in the pre-ovulatory stage. Moreover, too much insulin is the root of the problem. The polycystic ovaries’ cysts are ultimately caused by a follicular arrest brought on by excessive insulin.

Hence, once more, if we analyze the pathophysiology of PCOS, we find polycystic ovaries, an excess of testosterone, and anovulatory cycles. Everything is brought on by excessive insulin, which is also crucial for the onset of obesity and Type 2 diabetes, two serious health problems that are unmistakably linked to PCOS.

Beyond the problems with fertility, other ailments associated with PCOS include acne, cardiovascular disease, sleep apnea, non-alcoholic fatty liver, insulin resistance, and Type 2 diabetes.[7] All these conditions are caused by excess hormone insulin. The key is hyperinsulinemia, which travels to the ovary and instructs it to create more androgens while locking the SHBG. This is illustrated in [Figure 8] a review article from the New England Journal of Medicine in a lovely fancy picture.[8]

Figure 8:: Basic pathophysiology of hyperandrogenemia in the polycystic ovary syndrome.[8] STAR: steroidogenic acute regulatory protein (StAR), GnRH: Gonadotropin hormone-releasing hormone, LH: luteinizing hormone, FSH: follicle-stimulating hormone, HSD: Hydroxy steroid dehydrogenase. SHBG: sex hormone binding globulin.

Old-fashioned therapy for PCOS called ovarian wedge resection involved cutting a small wedge off the ovary, preventing it from producing as much testosterone. Consequently, many of the symptoms would improve. However, once more, as we never properly treated the root cause (hyperinsulinemia), we are not improving the actual illness.

A recommended course of therapy includes IVF, birth control pills, insulin-secreting pharmaceuticals, and stimulating agents. Where in all of this have we genuinely given attention to the root cause and our efforts to treat it? This is not the solution. Hearing all the tales of ladies who want to become pregnant but cannot do so is depressing.

We must reduce insulin since it is too high. Moreover, because no medicine excels at accomplishing it, pharmacological therapies are not all that effective. The fantastic thing is that we can cure this problem without medications by first understanding the disease. Low-carb diets, ketogenic diets, and intermittent fasting should all be recommended to patients since they all work to lower insulin levels. They are only attempting to reduce insulin levels. Our insulin levels drop if we do not eat or consume ketogenic or very low-carbohydrate diets, which can reverse PCOS.[9-11]

CONCLUSION

This article opened my eyes to the fact that some diseases in medicine can be cured if we can identify their underlying causes. Only then we can develop a logical action plan. Understanding the true pathophysiology of PCOS will make it much simpler to reverse the condition. This article allows us to explore novel concepts not part of conventional medical practice.

AUTHOR CONTRIBUTIONS

Dr. Jonnalagadda Vihari

Contribution: Concepts, Design, Data analysis, Manuscript editing and review, Manuscript preparation.

Dr. Neerukonda Sriteja

Contribution: Concepts, Design.

Dr. Samir Sahu

Contribution: Manuscript editing and review.

Dr.Chandan Das

Contribution: Manuscript editing and review.

Dr.Siba Prasad Dalai

Contribution: Manuscript editing and review.

Dr.Debasmita Tripathy

Contribution: Manuscript editing and review.

Dr. Abhishek Prasad Dash

Contribution: Manuscript editing and review.

Dr. Uppu Pooja

Contribution: Definition of intellectual content, Literature search.

Dr. Sourav Maiti

Contribution: Definition of intellectual content, Literature search.

Dr. Sonam Samal

Contribution: Definition of intellectual content, Literature search.

Declaration of patient consent

Patient’s consent not required as patients identity is not disclosed or compromised

Conflicts of interest

There are no conflicts of interest.

Financial support and sponsorship

Nil.

References

  1. . Consensus on infertility treatment related to polycystic ovary syndrome. Hum Reprod. 2008;23:462-77.
    [CrossRef] [PubMed] [Google Scholar]
  2. , , , , , , et al. Prevalence of polycystic ovary syndrome in adolescents. Fertil Steril. 2013;100:470-7.
    [CrossRef] [PubMed] [Google Scholar]
  3. . Role of obesity and adiposity in polycystic ovary syndrome. Int J Obes (Lond). 2007;31:S8-13.
    [CrossRef] [PubMed] [Google Scholar]
  4. , , , , . Health care-related economic burden of the polycystic ovary syndrome during the reproductive life span. J Clin Endocrinol Metab. 2005;90:4650-8.
    [CrossRef] [PubMed] [Google Scholar]
  5. , , , , , , et al. Androgen levels during sequential insulin euglycemic clamp studies in patients with polycystic ovary disease. J Steroid Biochem. 1988;31:995-9.
    [CrossRef] [PubMed] [Google Scholar]
  6. , , , . Insulin action in the normal and polycystic ovary. Endocrinol Metab Clin North Am. 1999;28:361-78.
    [CrossRef] [PubMed] [Google Scholar]
  7. , , , , , , et al. Cardiometabolic aspects of the polycystic ovary syndrome. Endocr Rev. 2012;33:812-41.
    [CrossRef] [PubMed] [Google Scholar]
  8. , . Polycystic ovary syndrome. N Engl J Med. 2016;375:54-64.
    [CrossRef] [PubMed] [Google Scholar]
  9. , . The PCOS Plan In: Prevent and Reverse PCOS through Diet and Fasting. Canada: Greystone Books; .
    [Google Scholar]
  10. , . A Patient's Guide to PCOS: Understanding-and Reversing-Polycystic Ovary Syndrome New York: Henry Holt and Company; .
    [Google Scholar]
  11. , , , , , , et al. Ketogenic diet as medical prescription in women with polycystic ovary syndrome (PCOS) Curr Nutr Rep. 2023;12:56-64.
    [CrossRef] [Google Scholar]
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