INTRODUCTION:

One of the most prevalent endocrine illnesses in women is polycystic ovarian syndrome, or PCOS. It is identified by the presence of hypervascularized androgen-secreting stroma and enlarged ovaries with numerous tiny cysts. Menstrual irregularities, polycystic ovarian syndrome, obesity, infertility, acne, and hyperandrogenism are among the clinical signs. A clinical diagnosis of polycystic ovarian syndrome is defined by the presence of two or more of the following characteristics: polycystic ovaries, androgen excess, and chronic oligo- or an-ovulation.¹

The Stein-Leventhal syndrome was the initial name for the polycystic ovary syndrome. A dangerous condition known as polycystic ovarian syndrome (PCOS) causes the ovaries to swell and create numerous “cysts,” which are actually tiny, immature follicles. The ovarian shell thickens and fibrose with time, preventing any ripening follicles from releasing themselves. Infertility, insulin resistance, an ovulation, and irregular menstruation are all linked to PCOS. Acne, hirsutism, and weight gain are possible. As the illness worsens, it may be linked to endometrial cancer, obesity, Type 2 diabetes, cardiovascular disease, excessive cholesterol, and dysfunctional uterine bleeding.²

The polycystic ovarian syndrome is characterized by ovarian cysts that impede normal ovarian function. This disorder has a number of underlying symptoms, such as obesity or increased weight, high blood pressure, diabetes, dysfunction of the lipid profile, dandruff on the scalp or oily skin, dark-colored patches covering the skin on the neck and underarms, chronic pelvic pain, acne, increased levels of male hormones resulting in thinning hair, baldness following the male pattern, excessive growth of hair on the body and face, and, in the case of women, irregular bleeding, ovulation, and immature follicles.³

PCOS may coexist with metabolic abnormalities like dyslipidemia, insulin resistance, and consequently, disorders like diabetes, obesity, cancer, and infertility as well as coronary heart disease. In a healthy individual, reactive oxygen species and antioxidants are in balance; when this equilibrium is upset, oxidative stress results. It could result in various illnesses. Women with PCOS are more likely to develop cardiovascular disease due to increased oxidative stress.

There is a higher chance of reproductive problems in women with PCOS. This is one of the main reasons why women are infertile. Despite being beneficial, this type of treatment is highly expensive and can have a number of negative consequences, including weight gain, gastrointestinal problems, irregular menstruation, and elevated insulin resistance. Since ancient times, medicinal plants have received particular attention. As a result of multiple studies, valuable and helpful medicinal plants have been found today.⁴

An important shift has occurred in herbal therapy. It is battling to be acknowledged as a science a distinct area with a distinct personality. Demonstrating that herbal therapy can match other medical specialties in terms of the breadth of its scientific research and its applicability in real-world scenarios has become imperative. Herbal therapy has several advantages over conventional medication, including safety, less side effects, and a potentiating effect due to the existence of several active chemicals in medicinal herbs.

Pathophsiology:

It makes sense that there would be a connection between insulin and ovarian function—excess insulin causes the ovaries to produce androgens, which can cause an ovulation. The primary indicator of an ovarian anomaly is follicular maturation arrest. Elevated gonadotropin-releasing hormone (GnRH) and luteinizing hormone (LH) levels are indicative of PCOS, whereas muted or unchanged follicular-stimulating hormone (FSH) levels are present. The activation of the ovarian thecal cells, which results in an increase in GnRH, creates more androgens Prolactin levels are high in about 25% of PCOS patients. The goal of therapeutic interventions is to lower ovarian androgen production and insulin levels, which will ultimately raise or lower levels of sex hormone-binding globulin (SHBG). It is possible to properly treat the symptoms of PCOS with this increase in SHBG levels. According to studies, thecal cells in PCOS patients produce more levels of progesterone, testosterone, and 17-hydroxyprogesterone than do normal patients.⁵

The pathophysiology of PCOS has been explained by a number of ideas, including:

· A distinct malfunction in the secretion and action of insulin that results in hyperinsulinemia and insulin resistance.

· A primary neuroendocrine deficiency resulting in an increased amplitude and frequency of the LH pulse.

· A change in cortisol metabolism leading to increased adrenal androgen production; a failure in androgen synthesis that results in greater ovarian androgen production.

Nonetheless, it must be acknowledged that each of these is merely theoretical hints toward our comprehension of the intricate relationships between the metabolic, ovarian, and pituitary circuitry.⁶

PCOS is characterized by hyperandrogenism, infertility, lack of ovulation, increased level of LH, increased insulin resistance, decreased sex hormone-binding globulin (SHBG), and hirsutism, which can be seen and diagnosed by laboratory tests and ultrasonography.⁷ The exact cause of PCOS is yet unknown.

Figure 1: Role of Hypothalamic – Pituitary – Ovarian Dystruction In PCOS.

Signs and Symptoms:

PCOS symptoms might emerge in early adulthood, although they can also start soon after puberty. Due to an ovulation, women with PCOS usually experience irregular or skipped periods; nevertheless, some may develop ovarian cysts. Ovarian cysts, elevated testosterone levels, PCOS, and non-ovulation all have a plethora of symptoms.¹⁰ A patient must have at least two of the following conditions in order to be diagnosed with polycystic ovarian syndrome.

· Acne not associated with puberty.

· Darkening of the skin

· Excessive hair growth (Hirsutism)

· Fatigue

· Fluid retention

· Heavy or prolonged periods

· Infertility

· Irregular periods

· Male pattern baldness

· Menstrual pain

· Mood swings

· Ovarian cysts

· Weight gain

· Miscarriage

Other Psychological Symptoms: In addition to depression, women with PCOS may also experience other psychological symptoms.

1. Hirsutism: Up to 70% of women with PCOS experience hirsutism, a frequent clinical manifestation of hyperandrogenism. The face, arms, back, chest, thumbs, toes, abdomen, and relation to PCOS owing to hormonal fluctuations are among the areas affected by excessive hair growth.⁸

Hyperandrogenism: In women, hirsutism and excessive terminal hair growth in androgen-dependent body parts are the most prevalent clinical manifestations of hyperandrogenism. Additional clinical presentations of hyperandrogenism consist of acanthosis nigricans, weight gain, menstrual abnormalities, and acne vulgaris.

2. Obesity: According to reports, patients with PCOS most frequently exhibit obesity (33%–88%). Obesity has a negative effect on fertility and can result in menstruation problems, anovulation, infertility, and abortion, among other problems. Therefore, it is crucial to control weight in the early stages of PCOS in order to enhance quality of life and the potential to bear children.⁹

3. Infertility: Forty percent of women with PCOS experience infertility. The most typical cause of an ovulatory infertility is PCOS. Primordial follicle counts in PCOS-affected women are normal, while primary and secondary follicle counts are markedly elevated. However, as soon as follicles achieve a diameter of 4–8 mm, follicular growth is stopped due to abnormalities in components involved in normal follicular development. Ovulation doesn't happen because a dominant follicle doesn't grow. Furthermore, spontaneous abortion is more common in PCOS patients, with rates ranging from 42% to 73%.¹⁰

4. Irregular Menstruation: The length and irregularity of the menstrual cycle are characteristics shared by all three PCOS classifications. Higher androgen and lower sex hormone binding globulin (SHBG) levels have been linked to longer and irregular menstrual cycles. This changed hormonal milieu may raise the risk of particular histologic subtypes of ovarian cancer ^[11]. Individuals could also have abnormal menstruation is characterized by irregularities in the menstrual cycle, severe irregularities, sporadic irregularities, brief, mild menstrual episodes, or bleeding.¹²

5. Ovarian Cysts: The most frequently identified intra-abdominal tumour in female fetuses is an ovarian cyst. Fetal ovarian cysts can produce ovarian torsion with a potential danger of losing an ovary or ovarian function, despite the fact that they are usually benign and generally resolve on their own. Management during pregnancy is still debatable because ovarian torsion frequently happens prior to delivery.¹³ An ovarian cyst that is less than 20 mm in diameter is regarded as normal and is an indication of a developing follicle. A cyst that is larger than 20 mm is regarded as abnormal. The incidence of ovarian cysts found in a fetus has increased with increasing ultrasound resolution, and it is currently believed to be about 1 in 2500 live births.

Diagnostic Test:

1. Ovulatory dysfunction and irregular menstrual cycles (in adolescence):

An ovulation and oligomenorrhea are essential components in the diagnosis of PCOS in adult females. In order to diagnose PCOS in adult women, oligomenorrhea/amenorrhea was a prerequisite under the original PCOS diagnostic criteria, known as the NIH criteria. Menstrual irregularities are nearly universally required for the diagnosis of PCOS in teenagers, according to a systematic study assessing diagnostic criteria for the condition during adolescence. An ovulation has been utilized as a diagnostic criterion for PCOS in a number of studies including adult women. This condition may be the result of a physiological event that happens in certain menstrual cycles in the early postmenarcheal years. Menstrual abnormalities are linked to increased blood pressure, a higher body mass index (BMI), and decreased insulin sensitivity. Menstrual irregularities at a young age may indicate a higher metabolic risk as a young adult, according to a prospective study that found adolescents with three or more menstrual cycles longer than 42 days at the age of 14 had higher BMI, insulin, glucose levels, and insulin resistance at the age of 25.¹⁴

2. Polycystic Ovary Morphology (PCOM):

The term “polycystic ovary morphology” (PCOM) refers to larger ovaries with a higher number of tiny peripheral cysts and stroma. Using a transvaginal probe and high-resolution technology, the Androgen Excess–PCOS Society Task Force advised that PCOM be classified as 20 follicles per ovary. However, due of the increased gonadotropin stimulation that results in increased ovarian volume and follicular proliferation, adolescent girls’ ovaries seem multifollicular, making it challenging to determine ovarian morphology in them. Furthermore, adolescent girls have trouble using transvaginal probes. PCOM in teenage girlsis an erratic result that is unrelated to anovulation or abnormalities in metabolism. Therefore, in adolescent girls, ovarian ultrasounds are not necessary.¹⁵

3. Pelvic Ultrasound to Evaluate PCOM:

Although PCOM and pelvic ultrasonography are included in the Rotterdam diagnostic criteria for PCOS in adult women, it is not advised to use them to diagnose PCOS in adolescents because they may lead to an overdiagnosis of the condition at this stage of life. Be aware that individuals with a gynecological age of less than 8 years are not suggested to utilize pelvic ultrasonography for the diagnosis of PCOS, according to worldwide evidence-based standards. Pelvic ultrasonography should not be used in adolescents for two main reasons. The first is that the majority of ultrasounds are performed trans-abdominally rather than trans-vaginally, which compromises the accuracy of the results.

Herbal Remedies for PCOS:

1. Ashwagandha:

Botanical Name: Withania somnifera

Family: Solanaceae

Ashwagandha powder is one such ayurvedic herb that has long been acknowledged as astrong adaptogen. Herbs known as adaptogens help the body balance hormone levels, which may reduce stress and symptoms associated with PCOS.¹⁶

The adaptogenic (anti-stress) properties of ashwagandha support thyroid and hormone balance, improve adrenal function, return cortisol levels to normal, and regulate insulin levels in the body. Ashwagandha can assist with PCOS-related anxiety and depression symptoms. By attaching to GABA receptors, ashwagandha has a soothing, anti-stress, and incredibly stabilizing impact. Moreover, ashwagandha root contains tryptophan, a building block of serotonin, the hormone that elevates mood. In addition, it treats irregular menstrual periods and decreases menstrual pain. Stressful situations raise blood cortisol levels, which are decreased by ashwagandha. It restores physiological functions under stressful circumstances by addressing the hypothalamic-pituitary-adrenal gland axis and re-establishing the proper balance between the immunological and neuroendocrine systems. Ashwagandha can assist with PCOS-related anxiety and depression symptoms. By attaching to GABA receptors, ashwagandha has a soothing, anti-stress, and incredibly stabilizing impact. Moreover, ashwagandha root contains tryptophan, a building block of serotonin, the hormone that elevates mood. Additionally, it treats irregular menstrual periods and decreases menstrual pain. Stressful situations raise blood cortisol levels, which are decreased by ashwagandha. In addition to lowering apoptosis, ashwagandha stops the development of new cancer cells. Flavonoids found in W. somnifera root extract and leaves exhibit hypoglycemic and hypolipidemic properties. Ashwagandha lowers cholesterol while increasing urine volume and salt content. The main function of Withania somnifera extract is to improve hormonal balance and stimulate the release of gonadotropin-releasing hormone.²⁸ Additionally, ginseng helps with sleeplessness, anxiety, and despair that are common with postmenopausal symptoms. In addition to its ability to alter the estrus cycle and its strong estrogenic effects-which are indicated by the reversal of atrophy of the vagina and uterus and the increased expression of ERα and ERβ in the reproductive tissue—it is frequently utilized as a natural estrogen replacement therapy. Positive characteristics of ginseng include all those mentioned above, which may help treat PCOS.¹⁷ Indian ginseng or Withania somnifera, has been used as a geriatric tonic and aphrodisiac in traditional medicine.

2. Pomegranate:

Botanical Name: Punica granatum

Family: Punicaceae

One of the fruits provides a variety of therapeutic benefits. The fruit has organic acids, sugars, pantothenic acid, vitamins B2, C, and B1, and folic acid. Both saturated and unsaturated fatty acids are said to be present in the seed. Using a control and PCOS group of adult female rats, the impact of pomegranate extract on the management or control of PCOS was investigated. The levels of andrestandoin hormone, serum estrogen, and free testosterone concentration were observed in the experimental group. According to the study, pomegranate extract may be able to mitigate the hormonal imbalances associated with polycystic ovarian syndrome. The extract’s phytosterols and phenolic components have a beneficial impact in reducing PCOS problems. According to the study, consuming the extract can lessen PCOS-related difficulties. Blood levels of free testosterone, serum estrogen, and androstenedione hormone were normal in women whose usual diet included Punica granatum. Punica granatum has been the subject of numerous studies, and the results indicate that using it helps to lessen PCOS issues. Among the main symptoms seen in women with PCOS are also decreased insulin sensitivity and high blood glucose. Consequently, medications that improve insulin sensitivity are part of the PCOS therapy regimen. Pomegranates have a long history of being associated with high antioxidant properties as well as a variety of pharmacological actions, including antiviral, anti-diabetic, antibacterial, anti-atherosclerotic, antiepileptic, and antihepatoprotective effects.

3. Spearmint:

Botanical Name: Mentha spicata

Family: Labiatae

Spearmint’s antiandrogen qualities have been shown and verified. Mentha spicata recommended for ladies with PCOS. Because M. spicata is beneficial for PCOS’s metabolic and reproductive problems. Alpha-glycosidase inhibition by alkaloids lowers intestinal glucose transport while glucose tolerance and release are increased by carbohydrates. Therefore, M. spicata functions as an anti-diabetic drug by inducing the synthesis of insulin, increasing its release and use, and decreasing the absorption of glucose from the intestine. In PCOS ovarian cysts, spearmint decreases atretic follicles and enhances graafian follicles. It has anti-cancer, anti-diabetic, and anti-inflammatory properties. The blood ratio of LH/FSH is modulated by mentha. Based on this alteration of LH/FSH in the blood, it might be useful in treating PCOS. Preclinical research has shown that spearmint has anti-androgen properties.¹⁸ Flaxseed and spearmint have been suggested and used to treat PCOS. Due to spearmint’s anti-androgenic properties, it has been observed that treating PCOS patients with spearmint significantly reduced their testosterone levels. In a case study, women with PCOS showed lower levels of androgen after consuming spearmint hydroalcoholic extract. According to a different study, spearmint can help people with hirsutism by lowering their levels of DHEA, LH, and FSH.¹⁹

4. Flaxseed:

Botanical Name: Linum usitatissimum

Family: Linaceae

The usage of herbal remedies, such as Linum usitatissimum (flaxseed), has increased in response to the rising prevalence of PCOS and has demonstrated encouraging outcomes in the management of the condition. Due to the presence of Secoisolariciresinol Diglucoside (SDG), which has an anti-inflammatory effect on humans, flaxseeds (also known as lentils) are a high-fiber, food high in omega-6, 3 fatty acids (alpha linolenic acid, or ALA) that have been shown to benefit insulin concentration, inflammation, and oxidative stress by reducing lipid peroxidation through their antioxidant activity. Prior research indicates that a 12-week supplement of omega-3 fatty acids derived from flaxseed oil improves hyperinsulinemia by suppressing pro-inflammatory mediators, lowering very low-density lipoprotein (VLDL) cholesterol levels, and reducing the activation of the nuclear factor-kappaB (NF-kB) transcription factor. It also lowers triglyceride levels by raising lipoprotein lipase activity. The PCOS symptoms improved as a result of all these adjustments. This was also noted in a randomized controlled trial conducted in 2020, the findings of which indicated improvement in metabolic syndrome, which can be treated with flax seeds because it is linked to PCOS.²⁰

Therefore, consistent flaxseed consumption through dietary supplementation may considerably reduce ovarian volume and follicle size in the ovaries and control menstrual cycle frequency. Additionally, it is utilized to treat a variety of illnesses, including neoplasms, diabetes mellitus, arrhythmia, obesity, and blood vessel clotting issues. Additionally suggested uses for flaxseed include the management of endocrine disorders and the control of female sex hormones.

5. Shatavari:

Botanical Name: Asparagus racemosus

Family: Asparagaceae

In the conventional practise of ayurveda, women utilize the medicinal plant for infertility, menstrual cycle management, ovarian follicle development, and optimal functioning. It is thought that the plant contains phytoestrogen, a naturally occurring plant-based estrogen that helps women’s reproductive systems function again. In the event of hyperinsulinemia, it also aids in the body’s regulation of insulin. The Shatavari effect has been observed in young PCOS women. According to a study, the plant is thought to boost folliculogenesis by improving the hormone that stimulates folicle growth. According to some studies, the weight in the ovaries may also rise. As such, they have a general tonic and a tonic for female reproduction. Shatavari contains a variety of chemical ingredients that are found in the leaves, stem, blossom, roots, and shoots of the plant; however, the root is thought to be crucial for significant or medical uses since it acts as a diuretic and has cytoprotective properties that help prevent ulcers. Shatavari is referred to as the “queen of herbs”. In the same way as within benefits male fertility, shatavari is a potent herbal remedy that is genuinely restorative for female fertility. The following are the numerous activities that Shatavari demonstrated:

1. Shatavari has extremely effective effects as a feminine tonic, reviving vitality and influencing desire in both sexes.

2. It aids in lowering genital organ inflammation and fatigue.

3. Shatavari maintains the ideal pH and hydration levels, which helps the dry tissue of the female reproductive organs.

4. Shatavari influences postpartum action by boosting lactation, which aids in uterine and ovarian hormone maintenance and balance for the mother.

Dried plant roots are used as medicine because they contain phytoestrogen. It rejuvenates the female reproductive system, controls the menstrual cycle, and promotes the development of ovarian folliclesShatavari’s effects on the reproductive system include: Nervous system stimulation; Support for the body’s hormone production and maintenance. Shatavari, on the other hand, is a herb that supports the HPO axis and plexus and works to balance the hormones that are upset in PCOS, hence preserving hormone levels. Shatavari also increases blood flow during menstruation, the length of the menstrual cycle (3 to 7 days), and the interval between the menstrual cycles (28 to 35 days).

6. Fennel:

Botanical Name: Foeniculum vulgare

Family: Umbelliferae

Studies have shown that F. vulgare has a beneficial effect on lactation by increasing milk secretion. Whereas infantile and abdominal colic is treated with fennel powder extract. According to the literature study, fennel has a well-established and promising role in treating a number of illnesses, including amenorrhea, PCOS, vaginal atrophy, menopause, dysmenorrhea, and infertility. We are here and are aware of the significance of fennel in the treatment of women’s health concerns. The benefits of fennel essential oils include improved genital function, infertility, and uterine contraction. The fennel exhibits a moderate increase in the number of follicular and multilayered follicles, as well as an improvement in the ovaries’ folliculogenesis process. According to this study, eating fennel fruit on a daily basis may help increase fertility, while fennel powder extract is useful to treat infantile and stomach colic. According to study, eating fennel fruit every day may help women become more fertile and may also lessen the symptoms associated with irregular menstruation. Fennel is a herbal plant that may have showed pharmacological effect because of its estrogenic properties. Because of its anti-hirsutism qualities and ability to lower levels of androgen (male hormones), fennel seeds are believed to be beneficial in the treatment of PCOS.

7. Fenugreek:

Botanical Name: Trigonella foenum-graecum

Family: Fabaceae

It reduces the size of cysts and the volume of ovaries in women who took it as a dietary supplement on a regular basis for ninety days. It also decreases the LH/FSH ratio; oral supplementation was found to significantly maintain the menstrual cycle. These outcomes suggest that this herb may be important and useful for PCOS. 15–28% protein, 6–12% fat, 4-8% ash, 8–16% fiber, and 0.2–0.3% essential oil are the remaining ingredients. The main elements of fenugreek seed oil that inhibit cysts include camphor, neryl acetate, β-pinene, and β-caryophyllene. The fenugreek seed is high in sesquiterpenes, n-alkanes, and certain oxygenated components when it comes to volatile oil. Additionally, it contains alkaloids (choline, trigonelline, and carpaine), saponins (fenugreen, foenugraeci, trigono sides, glycoside, yamogenin, smilagenin, yucca genin, sarsasapogenin, hederagenin, tigonenin, diosgenin), terpenoids, and flavonoids (naringenin, saponarin, lilyn, kaempferol, isovitexin, orientin, vitexin, isoorientin, luteolin, and quercetin). Women who took two capsules daily through diet showed improvement in PCOS symptoms, according to clinical investigations. Women who took anisum had smaller cysts and smaller ovaries.

8. Nirgundi:

Botanical Name: Vitex agnus-castus

Family: Lamiaceae

It helps treat irregular menstruation, PCOS, and infertility since it includes a specific amount of essential oil, alkaloids, and other phytoconstituents. This herb can help regulate ovulatory cycles and reduce hot flashes during menopause that are brought on by low progesterone levels. Nirgundi reduces inflammation, discomfort, and lack of appetite. The essential oil extracted from fresh leaves can be used to treat over 70 common and complex diseases. Menstrual cycle abnormalities and premenstrual syndrome, including cyclical mastalgia, postmenopausal hot flashes, and insufficiency of the corpus luteum, are indicative of an imbalance in estrogen levels.

9. Aloe vera:

Botanical Name: Aloe barbadensis

Family: Liliaceae

According to the current study on the effectiveness of aloe vera gel formulation in PCOS, the formulation restores the ovarian steroid status and modifies important steroidogenic activity, which protects against the PCOS phenotype. The phyto-components in the extract are responsible for this. It can also restore plasma lipoprotein levels, glycemic sensitivity, and the estrus cycle in addition to decreasing the liver’s production of cholesterol. Aloe vera is useful in treating PCOS brought on by metabolic problems since it also controls blood cholesterol and glucose levels.

10. Turmeric:

Botanical Name: Curcuma longa

Family: Zingiberaceae

Curcuminoids have a major impact on PCOS treatment. They lessen the follicular sheath and enhance the ovulation process and corpus luteum development. Turmeric thereby enhances the histological characteristics of polycystic ovaries. In women with PCOS, curcuminoids also raise the levels of estradiol and inhibit progesterone in the bloodstream. In PCOS-afflicted women, curcuminoids also raise estradiol levels while lowering progesterone levels in the blood. Additionally, its hypoglycemic, antioxidant, antihyperlipidemic, and estrogenic properties help to improve ovulation and fertility by preventing ovarian cell malfunction and treating PCOS.

CONCLUSION:

From adolescence to premenopause, PCOS is the most common hormonal condition in women. It can cause a range of consequences, such as infertility, metabolic and cardiovascular problems, and long-term health issues that may last a lifetime. Although synthetic drugs have demonstrated effective management for PCOS, their usefulness for a long-term cure is called into question due to significant adverse drug reactions. Patients are turning to herbal therapy instead of synthetic medications to improve recovery rates and acceptance when dealing with PCOS. This study provides a thorough examination of herbs that may be beneficial for treating PCOS and its related complications. We have examined different important medicinal herbs, their main chemical components, and how they are specifically important in managing PCOS. We believe that our assessment will be valuable for researchers studying herbal remedies for PCOS.

CONFLICT OF INTEREST: No

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Received on 10.04.2024 Revised on 13.06.2024

Accepted on 29.07.2024 Published on 17.12.2024

Available online on December 23, 2024

Asian Journal of Pharmaceutical Research. 2024; 14(4):374-380.

DOI: 10.52711/2231-5691.2024.00059

This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. Creative Commons License.