Polycystic Ovary Syndrome (PCOS): Exploring the Underlying Causes and Clinical Symptoms

Polycystic Ovary Syndrome (PCOS) is a chronic reproductive health condition that results from the abnormal functioning of the ovaries, which release estrogen, progesterone, and a slight degree of androgens. These hormones govern menstruation and ovulation as being governed by follicle-stimulating hormone (FSH) and luteinizing hormone (LH) hormones from the pituitary gland. Type-1 endometrial cancer has been linked with PCOS because women suffering from the syndrome have higher estrogen exposure than normal women of the same age. These factors include hypersecretion of luteinizing hormone, chronic hyperinsulinemia, and increased level of insulin like growth factors. Studies are still underway to determine the exact level of endometrial cancer risk in the women with PCOS. Further, there are also testimonial evidences that have linked PCOS to some forms of ovarian cancer. this is accompanied by hyperandrogenism and anovulation, which alter fertility and menstrual cycles in women. Hyperandrogenism and anovulation combined, frequently with hirsutism, acne, oligomenorrhea, infertility, and irregular uterine bleeding, are the hallmarks of PCOS.

Polycystic Ovary Syndrome (PCOS) is a hormonal disorder involves the production of excessive amounts of androgens in women as a result of the formation of small cysts. This disorder occurs among women of childbearing age and may develop during teenage years. A few of the complications associated with PCOS include; changes in hormone levels, irregular menstrual cycles, and fertility problems. For instance, it can be accompanied by obesity, insulin resistance, high androgen levels, and in most cases is genetically determined.

Although there is no treatment for the PCOS, most of the sign and symptoms may be controlled through diet changes, prescribed medication, and fertility therapies. It also results in anxiety, depression, and poor body image, thereby leading to Social exclusion and thus, the individual’s lives are affected in different ways especially in the areas of family, relationships and work. Although, it is believed to affect between 5% and 10% of women of reproductive age, many women with PCOS are not diagnosed.

History of Polycystic Ovaries

The illness known as polycystic ovarian syndrome, or PCOS, was initially identified by Stein and Leventhal in 1935 and is common among women who are of reproductive age. Stein and Leventhal formally described the PCOS in 1935 years after the condition was noted to affect the ovaries irregularly with cysts. Amenorrhea, obesity and hirsutism were linked by them to polycystic ovaries in seven patients – using this resultant term, they introduced the condition as “Stein–Leventhal syndrome”. Previous chronological accounts of ovarian similarity from Chereau beginning in 1721 and later reestablished in 1844 were not acknowledged until Stein and Leventhal’s more inclusive research.

Epidemiology of PCOS

PCOS is a hormonal condition that primarily affects women between the ages of 15 and 44 who are fertile. PCOS is affecting approximately 5-10% of women globally. PCOS affects between 2.2 and 26.7 percent of women in this age range. Many women are unaware that they have PCOS. Up to 70% of women with PCOS in one research had not received a diagnosis.

With an overall power ranging from 2.2% to 26% in Western nations, 2% to 7.5% in China, 6.3% in Sri Lanka, and 9.13% to 36% in India, the deep-rooted anovulation (CA) is prevalent in these regions. Individuals who have this problem are more likely to develop endometrial cancer, weight, dyslipidemia, cardiovascular disease (CVD), and insult resistance (IR). Hyperinsulinemia and insulin resistance are trained to treat the second-rate engrained basic aggravation

Etiology of PCOS

PCOS is a “syndrome,” or group of symptoms that affects the ovaries and ovulation.

· Ovaries being one of the important reproductive organs filled with cysts.

· High androgen levels, that is hormones present in males also known as the male sex hormones.

· One of the signs that suggest hormonal imbalance is the irregular or the so-called skipped periods.

A hormonal imbalance in PCOS leads to the growth of many tiny sacs called follicles, which contain immature eggs that do not develop enough to be released in the menstrual cycle. This affects the hormonal activity by decreasing the levels of estrogen and progesterone and increased FSH and LH thereafter affecting the cycle and causing fewer menstruations. PCOS was first diagnosed in 1721, by Antonio Vallisneri, who was an Italian physician.

Insulin also contributes to PCOS by promoting androgen production through the stimulation of theca cells of the ovary; inhibition of sex hormone binding globulin (SHBG); the resultant effect escalating free testosterone level. But, it is worth to note that insulin resistance is not present across all the PCOS patients, which further shows the multifactorial nature of the disorder.

Common Symptoms for PCOS Patients 

Polycystic Ovary Syndrome (PCOS) is a complex endocrine disorder that affects women in the reproductive years, 15-44 years of age, with higher estimates indicating that 50-70% of these women may remain undiagnosed. It affects the ovary, the organ which releases estrogen, progesterone and a little amount of androgens also. PCOS disrupts ovulation, controlled by follicle-stimulating hormone (FSH) and luteinizing hormone (LH), leading to three main symptoms: Cysts in the ovaries, high levels of male hormone and even missed or uneven menstrual cycle. The syndrome leads to the formation of numerous microscopic vesicles in the ovaries and a hormonal imbalance that also reduces the frequency of menstruation.

Symptoms of Polycystic Ovary Syndrome:

· Amenorrhea, oligomenorrhea, or hypomenorrhea This abnormality of the menstrual cycle may sometimes be expressed as amenorrhea, in which there is absence of the periods; oligomenorrhea refers to infrequent occurrence of the periods; while hypomenorrhea explains scanty and light periods. These symptoms include enlarged ovaries or multiple ovarian cysts.

· Having body hair on places where females generally do not have hair on their body such as chest, stomach and back.

· Obesity and central obesity are the common issues that are associated with increased mortality rates. 

· Acne or oily skin The type of skin is considered as the outer-most layer of our skin and it is composed of dead skin cells, skin oil, and various other substances that are found within our skin IRA.

· It is also become prevalent for men to lose their hair either through male-pattern baldness or thinning hair.

· Infertility.

· Melanosis – black or thick skin color change in the folds of the skin in areas such as neck, armpits, and under the breasts.

· Heavy bleeding: Compensated cycles or higher shedding with endometrial thickness attributable to prolonged presence of the endometrial lining.

· Weight gain: It is estimated that the PCOS affects around 5-10% of women of reproductive age, and up to 80% of these women could be overweight or obese

· Male pattern baldness: Hair loss and or thinning hair at the top of the scalp

· Darkening of the skin: Side effects skin issues: Under arm and other skin folds problems /dark skin color.

· Headaches: This is assocated with the fluctuating hormones in some female individuals.

Associated Health Conditions:

· Type 2 diabetes.

· Hypertension is a medical condition characterized by high blood pressure.

· High cholesterol

· Heart disease

· Endometrial cancer

Normal Vs Polycystic Ovary

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Hormonal Imbalance and Reproductive Complications in PCOS

An imbalance in reproductive hormones that results in the development of cystic ovarian follicles is the cause of PCOS. The eggs inside these fluid-filled sacs are not fully matured, which prevents ovulation and throws off the menstrual cycle, frequently leading to amenorrhea. Every cyst has a width of 8–10 mm. This inhibition of egg release lowers the likelihood of fertilization and pregnancy. There is a significant chance of miscarriage even in the event of implantation. Other issues including as pre-eclampsia, hypertension, gestational diabetes, and early birth can also result from PCOS.

Pathophysiology of PCOS   

The pathophysiology of PCOS has not been definitely elucidated however, there is altered insulin signaling and apparent metabolic dysfunction even in non-obese females. Hyperinsulinemia causes increased concentrations of insulin, and impacts on the rate of androgen synthesis by effecting the protein binding, thus leading to high levels of free androgen content. This hormonal change alters the visible features of the ovaries and its abilities, which results to fertility. Said to be associated with Obesity which in return is linked to the PCOS in a causal cycle, the insulin resistance is known to be aggravated if one is obese. Weight gain contributes to worsening PCOS and making it more severe but engagement in exercises and taking modified diets enhances insulin sensitivity.

The premise for the pathophysiology of PCOS is the increase in levels of free testosterone that subsequently result in hyperandrogenism. This causes hormonal imbalances especially in the ovaries and hence there is problem in ovulation and fertility. Neuroendocrine influences, dietary habits, genetic susceptibility, hormonal exposure, lifestyle and environmental factors have been found to play a role in the pathogenesis and management of PCOS and its complications. Knowledge of these mechanisms is therefore important when managing and treating people who have developed PCOS.

https://www.researchgate.net/figure/Pathophysiology-of-polycystic-ovary-syndrome_fig2_357920670

PCOS genetics

Moreover, genetic factors are proved to be important since mutations of SNP genes, CYP19 and CYP11A1 genes in particular, are involved in PCOS development and worsening. Some of these genetic changes cause hormonal abnormalities that predispose women to develop some types of cancer such as endometrial and breast cancer.

PCOS and Psychological Symptoms

Recent studies have identified that 42 percent of women with Polycystic Ovary Syndrome (PCOS) suffer from depression, though its pathophysiological factors comprise insulin resistance, hypothalamic-pituitary-adrenal axis dysregulation, hyperandrogenism, obesity, and infertility. Diet modifications and weight loss; psychological therapy by cognitive behavioral therapy; and anti-depressants are useful interventions for managing PCOS related depression. Increasing evidence show that the prevalence of depression in women with PCOS has risen in the last decade required improved comprehensiveness and management strategies.

The PCOS is an endocrine disorder affecting up to 80% women in reproductive age group and its symptoms include amenorrhea, hirsutism, infertility, obesity, acne and androgenic alopecia. This specifically affects a woman’s social status, psychological wellbeing, and general well-being. The anxiety and depression in PCOS are therefore complex and highly associated with factors such as acne, hirsutism and obesity. Despite this, the pathophysiology of PCOS remains unclear with questions still existing about the natural history, range of symptoms that may develop in the course of the disease, and the severity of morbidity.

PCOS affects body by following ways:

PCOS and Infertility

Taken with the fact that PCOS is one of the biggest causes of female barrenness due to hormonal imbalance causing infrequent ovulation and thus fewer eggs to be fertilized. Available therapeutic options include the use of insulin sensitizers such as metformin, rosiglitazone, and pioglitazone; however, there is controversy regarding the therapeutic effectiveness of metformin, rosiglitazone, and pioglitazone compared to clomiphene. According to previous research, metformin appears to be more beneficial than clomiphene for achieving better results in fertility treatment, conversely, other researchers opine that, treatment based on clomiphene can result in better live birth rates. The use of metformin and clomiphene in combination has been reported to have variable effectiveness, including, one study proposed the possibility of its better efficacy than using clomiphene alone.

 PCOS and Weight Gain

Unhealthy food intake and poor exercise habits are some of the possible causes of obesity in women with PCOS, which is commonly caused by high insulin levels that subsequently stimulate androgen production, resulting to other symptoms such as excessive hair growth and acne, irregular menstrual cycle and severe weight gain in the abdomen. Approximately, obesity especially in the abdominal region is proven to cause diseases like heart diseases among others.

PCOS and Metabolic Syndrome

This cardiovascular metabolic disorder is more likely to occur in women with PCOS and those who are obese, and is identified by high blood pressure, low levels of HDL cholesterol or good cholesterol, elevated levels of LDL cholesterol or bad cholesterol, and high insulin resistance. These activities increase the chances of developing diabetes and angina pectoris.

PCOS and Sleep Apnea

Researchers point out that women with PCOS, particularly overweight ones, who are at high risk of developing sleep apnea, a condition in which breathing is interrupted during sleep. MSA is found to be at a much higher risk amongst obese women with PCOS than among those who do not have the syndrome.

 PCOS and Cancer Risk

PCOS brings about endometrial cancer risks as a result of hormonal unbalances and in this case, the use of hormonal contraceptives and change of lifestyle are recommended. However, several studies have pointed at PCOS as a relationship with ovarian cancer, and this is where the use of oral contraceptives may prove helpful. Insufficient evidence exist in the literature to compare the risk of women with PCOS to those with other forms of cancer.

PCOS and Insulin Resistance

The metabolic disorder such as insulin resistance has been found in PCOS with up to 70% prevalence. It results in increased insulin; the ovaries are then stimulated to produce more male hormones. It is also important to note that obesity is a major risk factor for development of type 2 diabetes and that insulin resistance also contributes to this condition.

PCOS and Inflammation

Polycystic ovarian syndrome (PCOS) is associated with inflammation in most women and is made worse in courses with unhealthy weight. The research also established that high levels of androgens are associated with high inflammation in PCOS patients.

Causes of PCOS

Till date there is no clear understanding of what exactly leads to PCOS, but various aspects have been found to be in some way related to development of it. Some of the causes may be hereditary, that is, have existed in the original family; besides changing a lifestyle, getting a job, moving to another city, or country; inactivity, shift towards or away from high fiber diet, increased or decreased work pressure, polluted environment, and stress. Among them, stress has been found to be contributing to PCOS most evidently that results to hypertension, type 2 diabetes, increased susceptibility to uterine cancer and cardiovascular diseases. Today, despite studies carried out on genetic aspect associated with PCOS, the disease presents it complications differently in different people, making the accurate cause a subject of controversy.

PCOS is multifactorial disorder in which various factors can play a role like genetic, environmental factors and diet attitudes. Several environmental causes like use of certain chemicals such as triclosan in personal products can lead to its development (Lai, Ye et al. 2022).

Multiple causes are associated with Polycystic Ovary Syndrome (PCOS), including genetics, environment, and sex hormones. On the basis of these investigations, it has been observed that genetic predisposition, insulin resistance, and inflammation play a vital role in the endocrine dysfunction. Research indicates that the genetic system that underlies the development of PCOS is multifactorial, including multiple genes. Type 2 diabetes and insulin resistance, present in 60-70% of women suffering from PCOS, cause increased insulin levels promoting the production of androgens. Also, inflammation that is commonly linked to obesity contributes to hormonal issues as well. 

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Management of PCOS

Some of the potential remedies might therefore include vitamin D and calcium supplements, flaxseed, licorice root, Rhizoma coptidis, and Nicker Bean for instances managing the occurrence of PCOS. Nevertheless, there are gaps in knowledge pertaining to hormonal disruptions including the hypothalamus-pituitary-gonadal axis affected by hormonal contraceptives, lactation, insulin-sensitizing agents, reproductive development both in males and females, and pregnancy.

Millions of women worldwide suffer from PCOS, a multifaceted disorder marked by symptoms like insulin resistance, irregular menstruation, and hyperandrogenism. Although there are conventional medicines, research into natural alternatives is prompted by the adverse effects of these treatments. Plants such as grapes contain a polyphenol called resveratrol, which has anti-inflammatory, anticarcinogenic, and antioxidant qualities. It also promotes ovulation by preventing the overproduction of ovarian androgens. Quercetin is a flavonoid that has anti-inflammatory and antioxidant properties. It also lowers LH and testosterone levels and increases insulin sensitivity. Furthermore, 6-gingerol, which comes from ginger, has anti-inflammatory and antioxidant properties that increase estradiol levels and reduce ovarian cysts. Through the correction of hormone imbalances and symptom mitigation, these natural extracts present a viable route for the treatment of PCOS (Hajam, Kumar et al. 2023).

PCOS Diagnosis and Treatment

Diagnosis usually requires the identification of clinical signs including symptoms like high levels of androgens, disturbed menstrual cycle and ovarian cysts mostly by blood tests and ultrasound. Some remedies include contraceptive pills, metformin, letrozole, spironolactone, clomiphene, medications for hair removal surgeries, and surgical needs such as ovarian drilling or wedge resection depending on the patient’s objective.

PCOS Treatment

There is available many different kinds of treatments for PCOS, aimed at the symptom control, hormone balance, and fertility improvement. Common treatment is taken in the form of birth control pills to help balance hormonal levels; Metformin to enable enhanced insulin sensitivity, and Clomiphene to stimulate ovulation. If other methods are unproductive, the doctors may require the woman to undergo operations such as ovarian drilling. The outlined lifestyles include exercise, a healthy diet, weight management, and smoking cessation, which are necessary in the management of PCOS. Blood Tests and Hormonal Assessments are mandatory.

Lifestyle changes are the foundation for intervention wherein patients are encouraged to adopt healthy weight control, optimal eating habits, adequate physical activity, stress management, and elimination of irresponsible behaviors such as frequent consumption of fast foods or taking alcohol. These are the recent developments in the management of PCOS where the current possible treatments consist of oral contraceptives, antiandrogen like cyproterone acetate and insulin-lowering like metformin. These drugs work towards achieving normalization of hormones, beautifying symptoms such as hirsutism, abnormality that characterizes menstrual cycles and fertility health.

Future Directions and Research

Treatment plans for PCOS have been changing over the years, due to the variations observed in the condition. Pharmacologically, certain presentations like anovulation or hirsutism might be addressed through specific treatment interventions. In hirsutism, the methods of managing the hairs are by removing them and the antiandrogen where the commonest one is spironolactone. ORMP commonly used for anovulatory women has in the past included drugs such as clomiphene citrate or metformin. Weight loss interventions have also come out freely; this is due to the fact that Obesity worsens insulin resistance and hormonal balance that is common among women with PCOS. Medical therapies for PCOS are considered to be crucial intervention strategies, and should be combined with guidelines regarding diet, physical activity and weight loss in order to enhance their impact and patients’ quality of life.

Conclusion:

PCOS a multisystem and complex endocrine disorder of genetic basis significantly affect fertility and metabolic functions in women. The signs and symptoms of which are: Irregular menstruation, hirsutism and infertility can alter life expectancy to a great extent. Even though the condition is easily manageable through diet and medication and other nonpharmacological measures, more women are still not screened early enough, and as a result they receive inadequate treatment. Clinicians must have adequate awareness of the various forms of PCOS to provide the right diagnoses and/or administrative measures. The signs and symptoms of PCOS reach beyond pure fertility, although its reach extends into other areas of a woman’s fertility and volume metabolic and psychological health over her entire lifespan. Some of the more important ones are insulin resistance, increased androgen levels, and hormonal balance in the gonads. Stress runs a risk of worsening PCOS, increasing possibilities of disorders which include diabetes, hypertension, as well as cardiovascular diseases. Enzyme markers are helpful in identification of the disease since the major hormone levels include elevated androgens, lutenizing hormone, Prolactin and estrogen. Treatment consists of the above and patients can take oral contraceptives, insulin-lowering medications, progestin therapy, and weight loss management.

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