PCOS or PMOS (Polyendocrine Metabolic Ovarian Syndrome What We Know And What We Can Do.
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It is characterized by ovarian cysts, irregular ovulation, and hormonal imbalances, manifesting as menstrual irregularities, infertility, excessive androgen levels (leading to conditions such as hirsutism), and metabolic disturbances. Women with PMOS are at an elevated risk of developing serious health issues including type 2 diabetes, cardiovascular diseases, and endometrial cancer. It affects over 116 million women worldwide, or approximately 3.4 % of the global female population
PCOS has been renamed polyendocrine metabolic ovarian syndrome (PMOS) to better reflect its multisystem nature as a complex endocrine and metabolic disorder rather than a condition defined by pathological ovarian cysts. This change resulted from a 14-year global consensus process involving more than 50 professional societies and patient organizations.
Stein and Leventhal were the first to recognize an association between the presence of polycystic ovaries and signs of hirsutism and amenorrhea (eg, oligomenorrhea, obesity). After women diagnosed with Stein-Leventhal syndrome underwent successful wedge resection of the ovaries, their menstrual cycles became regular, and they were able to conceive. As a consequence, a primary ovarian defect was thought to be the main culprit, and the disorder came to be known as polycystic ovarian disease.
In 2023, the International PCOS Network released evidence-based guideline criteria, which require the presence of two of the following to diagnose it:
Clinical and/or biochemical evidence of hyperandrogenism.
Ovulatory dysfunction.
Polycystic ovaries as indicated by ultrasound examination or anti-Müllerian hormone (AMH) level in adults.
Neither ultrasonography nor measurement of serum AMH is recommended in adolescents because of poor specificity in this age group.
It can be diagnosed in patients who have both irregular menstrual cycles and hyperandrogenism. In such patients, neither an ovarian ultrasound scan nor an AMH level is required for the diagnosis.
Although the exact cause of this condition is unclear, PCOS can result from abnormal function of the hypothalamic-pituitary-ovarian (HPO) axis. A key characteristic of PCOS is inappropriate gonadotropin secretion, which is more likely a result of, rather than a cause of, ovarian dysfunction. In addition, one of the most consistent biochemical features of PCOS is a raised plasma testosterone level.
Current status
What causes is not authoritatively established. Because it cannot be cured, management primarily focuses on mitigating individual symptoms—such as fertility, metabolic dysfunction, irregular menstrual cycles, and hyperandrogenism (e.g., acne and excess hair growth).
Pharmacotherapy for PCOS
Several drugs used for the treatment of PCOS are not devoid of harmful effects on patients. The issues that are linked with clomiphene citrate (CC) are also something that should be taken under consideration. These concerns include the potential danger of ovarian cancer, the antiestrogenic effects it has on the endometrium, as well as the issue of the early LH surge. After using CC for an extended period of time, more than 12 treatment cycles, there is a possibility of developing ovarian cancer. As a result, this medicine should only be used for a maximum of six cycles. Moreover, clomiphene and letrozole do not exhibit anti-estrogenic effects on the endometrium and cervical mucus. Dehydration, excessive urination, vomiting, headache, lethargy, gastritis, and ovarian disruption leading to irregular menstruation are some of the side effects that may be caused by using spironolactone. Metformin use is linked to a wide range of adverse effects, including but not limited to nausea, vomiting, digestive disturbances, and ketoacidosis. Furthermore, in patients with PCOS, metformin therapy must be continued indefinitely because stopping the medication after a period of three months has the potential to reverse all the disease progress. A long-term intervention is required for PCOS treatment owing to the significant and severe adverse reactions of currently used drugs, which warrants the search for novel therapies for the chronic management of PCOS. For the treatment of PCOS, the use of plant-based medications, which have fewer potential negative side effects, is likely to become the most effective strategy.
Treatment for PCOS-related symptoms
It has been shown that making changes to one’s lifestyle, such as maintaining a healthy weight loss, increasing physical activity, and making adjustments to one’s food, can help in the management of PCOS. Spironolactone, metformin, and eflornithine are the drugs that are considered to be the first line of defence in the fight against hirsutism (51). Because they have a low androgenic effect, additional contraceptive pills and their combination of either progestins or norgestimate, desogestrel or drospirenone are frequently used to treat hirsutism. Contraceptive pills, spironolactone, acarbose, and rosiglitazone are the four most common medications used to treat menstrual problems.
In PCOS, whole ovarian hypertrophy is seen with thickened capsule (54). There is an increased number of sub-capsular follicle cysts (55–57). The main features of PCOS are:
Increase in ovarian size
Capsules that are thicker than 100 µm
An increase in the amount of subcapsular follicular cysts.
A deficiency in the number of corporea lutea or albicantia
Hyperplasia of the ovarian stroma, as well as fibrosis
Theca cell luteinization before its time.
Phytochemicals for PCOS management
Numerous studies have demonstrated the efficacy of herbal drugs and isolated phytochemicals for the management of PCOS. Several phytochemicals, such as curcumin, rutin and fisetin, regulate the reproductive cycle via reducing testosterone level, and LH to FSH ratio. Some phytochemicals also increase the insulin sensitivity and improve the glycaemic control, which contributes to the betterment of PCOS symptoms. Some essential oils such as α-thujone are antiandrogenic in nature, so they decrease the level of androgen while improving ovulatory functions. Puerin, fisetin, berberine reduce the features of PCOS and associated comorbidities by decreasing oxidative stress.
The alternate protocols:
Polyphenols
Curcumin and fisetin are two phytoconstituents that have demonstrated a significant reduction in the symptoms of PCOS. The lipids and hormonal profiles as well as insulin resistance are improved by these agents. In addition, the activity of enzymes that fight free radicals is increased by these plants.
Flavonoids
Flavonoids may be natural, citrus, or bioflavonoids. Flavonoids extracted from various plants are found to decrease testosterone levels, improve insulin resistance and increase the expression of IL-6 to treat PCOS rats. Several major flavonoids are used for PCOS management, namely resveratrol, hesperidin, quercetin, rutin, naringenin, and apigenin. These flavonoids decrease the levels of testosterone in the body. They also improve the insulin resistance and decrease the number of cysts in the ovary.
Resveratrol
Its effectiveness in the treatment of PCOS is well-established. It was discovered that resveratrol inhibited the production of CYP17 and CYP21 proteins as well as their enzyme activity to prevent excessive production of androgens in PCOS animals. Several research studies demonstrated that resveratrol exhibited PCOS ameliorating effect through decreased LH, LH/FSH, TNF-α and tissue AMH in diseased animals. In addition, resveratrol also increased E2, LH and testosterone, reduced the expression of mTOR and Akt in ovarian tissues to regulate reproductive function. For the purpose of determining whether or not resveratrol is effective in treating PCOS, a clinical trial was carried out on 78 individuals who received 1000 mg of the medication every day for a period of three months. After therapy, the results showed an increased menstruation rate and a decreased rate of hair loss, and the levels of lipids, insulin, and androgens remained the same.
Quercetin
Tea is a good source of quercetin. Oxidative stress is thought to be the primary component that leads to PCOS. The mechanism of action is an improvement of the NF-κB signalling pathway and a correction of the inflammatory environment of the ovarian tissue. PCOS has also been linked to dysfunction of the endocrine glands. Beside affecting insulin resistance, quercetin also alters gene expression of GLUT-4 and ER in diabetic pregnant mice to improve embryo development. Quercetin also decreased insulin resistance in PCOS rats via decreasing liver glucokinase and hexokinase, and increasing the expression of GLUT-4 and estrogen receptors. In women with PCOS, their levels of adiponectin tend to be lower, regardless of their weight (117). Eighty-four PCOS women were given quercetin, and their adiponectin-mediated insulin sensitivity was tested. When compared to placebo, taking quercetin 500 mg twice per day for 12 weeks resulted in a rise in total adiponectin by roughly six percent and an increase in the level of high molecular weight adiponectin by approximately four percent. There was a drop in the level of testosterone, LH and insulin resistance in the quercetin group, which emphasized the function of quercetin in remodelling the adiponectin-mediated insulin resistance and hormonal level in PCOS women.
Isoquinoline alkaloids
Some isoquinoline alkaloids alleviate insulin resistance and activate the insulin signalling pathway. Berberine is a major member of this family. It promotes the utilization of glucose and reduces the level of serum androgen. It improves sex hormone binding globulin levels. As an isoquinoline alkaloid, berberine is the main effective component of this class, as a multi-target, multi-path plant constituent that interferes with the development of PCOS and related comorbidities with a few adverse reactions. It was found that berberine reduced the expression of toll-like receptor 4 (TLR4), Src family tyrosine kinase (LYN), phatidylinositol 3- kinase (PI3K), NF-κB, TNF-α, IL-1, and caspase-3, which was accompanied by a reduction in cell apoptosis, which pointed to the potential significance of berberine in the therapy of PCOS.
Phytoestrogens
Phytoestrogens are substances that naturally occur in plants. They have a similar chemical structure to our own body’s oestrogen and are able to bind to the same receptors as that of oestrogen. Phytoestrogens have shown both estrogenic and anti-estrogenic effects. Isoflavones are the most widely studied phytoestrogens. These are abundantly found in soybeans, legumes, berries, grains, nuts, and wine. Resveratrol, found in fruits, berries, red wine, chocolate, and peanuts, is believed to be responsible for some of the health benefits that include improved hormonal profile, insulin resistance, and antioxidant effects. There is evidence that phytoestrogens like Biochanin A, Daidzein, Genistein, formononetin, and Puerarin can help in the management of PCOS symptoms. PCOS women experience a disruption in the process of the production of androgen as well as its metabolic process and oestrogen, which causes an increase in the concentrations of androstenedione, testosterone, and dehydroepiandrosterone in their serum. Phytoestrogens have molecular structures and sizes nearly identical to oestrogens such as 17-estradiol and diethylstilboestrol. As a result, these attach to oestrogen receptors and have anti-estrogenic effects, helping PCOS patients with hormonal imbalances. A randomized, double-blind, and placebo-controlled trial was carried out to demonstrate the effectiveness of soy-isoflavone and phytoestrogen against PCOS. Phytoestrogens consisting of 37.5 mg genistein, 10 mg daidzein, and 2.5 mg glycitein were given to PCOS patients for a period of 12 weeks. A considerable drop was seen in both the free androgen index, serum triglyceride, and insulin levels as a result of therapy with phytoestrogens. Additionally, a significant rise in plasma glutathione level and a fall in monoaldehyde level pointed towards a favourable effect of phytoestrogens on the management of PCOS.
Catechins
Green tea is derived from the plant Camellia sinensis and contains a high concentration of catechins along with several minerals and vitamins. It has several health benefits, including but not limited to effectiveness against diabetes, insulin resistance, and obesity. A total of thirty-four obese Chinese PCOS patients were selected at random to receive either treatment with green tea capsules or a placebo for a period of three months. After receiving therapy, each group’s anthropometric measurements and biochemical and hormonal profiles were compared to those taken before treatment. After treatment, little but noticeable weight loss among those who had consumed green tea without any noticeable variation in hormone levels.
Polyunsaturated and dietary short-chain fatty acid
Studies have shown that a decline in carnitine, a metabolic intermediate of fatty acids, causes oocyte maturation and regulates energy metabolism and transport of fatty acids. Polyunsaturated fatty acids, such as omega-3 and α-linolenic acid play important therapeutic role in PCOS through reduction of inflammation and oxidative stress, and normalizing hormonal irregularities. In addition, short-chain fatty acids including butyric acid, are usual breakdown products of dietary fibres by gut microbes, which affect cellular functions such as apoptosis, proliferation and adiposity by G-protein-coupled and other receptors. Butyric acid inhibited PCOS symptoms through reducing insulin resistance, ovarian inflammatory cytokines and gut microbiota. Butyric acid treatment of human granulosa tumour cells ameliorated lipopolysaccharide-induced apoptosis, inflammatory cascade and oxidative damage. In addition, intraperitoneal administration of butyric acid exhibited a decline in follicular count, LH, testosterone and insulin level, and increased FSH and estradiol level in obese PCOS mice.
Plants to treat PCOS
Several medicinal and dietary herbs and plants have been investigated for the management of PCOS. Several plants such as Vitex agnus, Cinnamomum genus, pomegranate, Tribulus terrestris, Mentha species and Nigella sativa have been investigated for their sub-clinical and clinical effectiveness to manage and treat PCOS symptoms.
Vitex agnus-castus
The Vitex agnus-castus (VAC) plant is a shrub or a small tree. The flavonoids make up the majority of VAC components. In vitro research has demonstrated that the flavonoids such as castidin, quercetagetin, and isovitexin have an effect on oestrogen receptors. VAC has been shown to be efficacious in both pre-clinical and clinical study for the reduction of prolactin levels, the improvement of the menstrual cycle, and the treatment of infertility. Compounds in VAC binds to dopamine type 2 (DA-2) receptors in the CNS, decreasing cAMP and prolactin release. In a research, women who had been trying to conceive for six to thirty-six months were given a supplement containing VAC. It is recommended to take between 500 and 1000 mg of dried berries and 1–4 ml of a tincture made from dried plants. After three months, the supplementation group showed significantly higher levels of mid-luteal progesterone and regular menstrual periods, in contrast to the placebo group, which showed no significant changes. 14 of the 53 women who took the supplement became pregnant, compared to only 4 of the placebo group’s 40 women who did not become pregnant.
Cinnamomum genus
As a condiment and aromatic plant, cinnamon is widely used. Its bark and leaves are used to make cinnamon oil. Its major bioactive components include polyphenols and cinnamaldehyde (131). It has been proven that the PCOS-treating properties of Cinnamomum zeylanicum include both reproductive and metabolic benefits. It was observed that cinnamonaldehyde had decreased the blood glucose through upregulating the expression of the GLUT4 gene. Cinnamaldehyde also increased the antioxidant response of reactive oxygen species produced in hyperglycaemia so as to safeguard pancreatic beta cells. PCOS patients receiving an extract of cinnamon three times a day for eight weeks experienced an improvement in their insulin sensitivity. The process for reducing insulin resistance involves increasing glucose utilization and potentiating the insulin signalling pathway via phosphatidylinositol 3-kinase (PI-3 kinase) at the post-receptor level. Recent clinical trial findings show that menstrual disruption in women with PCOS may benefit from cinnamon supplementation of 1500 mg/kg for 6 months. It is thought to be due to insulin resistance that improves and reduces menstrual irregularities
The Cinnamomum cassia (Chinese cinnamon) tree is a tropical evergreen tree that is fragrant. Terpenoids, phenylpropanoids, and glycosides are the primary chemical components found in Cinnamomum cassia. A placebo-controlled and randomized experiment was carried out for a total of eight weeks. This study was carried out on 15 obese women who were also suffering from oligomenorrhea or amenorrhea and PCOS. Participants received either 333 mg of Cinnamomum cassia extract or placebo in a tablet three times per day for the entire duration of the study. Insulin sensitivity was significantly improved in the therapy group. There was no significant difference between the two groups in terms of BMI, testosterone levels, or oestradiol levels.
Pomegranate juice
The majority of the phytoconstituents found in pomegranate fruit are polyphenols. 92 women with PCOS participated in a parallel, randomized, and triple-blinded study. Three treatment groups, each consisting of twenty-three patients, were given two litres per week of either symbiotic pomegranate juice (SPJ), pomegranate juice, or symbiotic beverage (SB). The patients in the control group were given two litres of a placebo beverage per week. At the conclusion of the research project, 86 patients were examined. Insulin resistance, BMI, weight, and waist circumference were decreased significantly in the treatment groups. Both the SPJ and SB groups demonstrated a considerable reduction in their testosterone levels. Any noticeable difference in the FPG, LH, or FSH levels between any of the groups was not evident.
Tribulus terrestris
In women with PCOS, the floral parts and fruits of Tribulus terrestris have been shown to increase the frequency of ovulation and decrease the size of ovarian cysts. The treatment with 10 mg of a hydroalcoholic extract of T. terrestris normalized the menstrual irregularity as well as hormonal changes. Additionally, the ovarian cysts were effectively eliminated and the normal function of the ovary was restored. In PCOS, the postulated mechanism of T. terrestris was the normalization of the hormonal balance and the induction of ovulation through antiestrogenic action. In a randomized control study, women who took 1000 mg of hydroalcoholic T. terrestris extract every day showed promising hypoglycaemic effects. Treated patients also had less total cholesterol and low-density lipoproteins, which showed therapeutic effectiveness of this crude drug against obesity-induced PCOS.
Mentha species
Mentha spicata (commonly known as Spearmint) and Mentha piperita (known as peppermint) are among the most widely studied species of Lamiaceae family for the treatment of PCOS. Both species have been evaluated for different reproductive health problems in women such as PCOS, amenorrhea and dysmenorrhea. These species have two major bioactive components; essential oils and phenols. Studies on spearmint extract demonstrated that it improved PCOS symptoms and ovarian histology against estradiol and letrozole induced PCOS disease models. Spearmint oil also increased follicular development at 150 and 300 mg/kg dose in PCOS rats through decreasing ovarian cysts, atretic follicles and testosterone level . Mentha piperita herbal tea (40 g/L) demonstrated the efficacy to treat PCOS in letrozole induced PCOS in rats and moderated letrozole induced fibrosis in ovary by decreasing estradiol level. Clinical trials showed that drinking spearmint tea (5 g in 250 mL water) twice a day for 30 days reduced testosterone levels (both free and total), and raised levels of LH and FSH. It is possible to draw the conclusion that Mentha spicata is a useful antiandrogenic treatment in patients diagnosed with PCOS because it lowers both free and total androgen levels and cuts down on the number of ovarian cysts.
Nigella sativa
Nigella sativa, also known as black cumin or black seeds, has been widely documented for its potential to treat PCOS. A previous study demonstrated that seeds extract of nigella improved the maturation of oocytes isolated from PCOS mice by inhibiting the expression of COX-2 and oxidative stress . The efficacy of Nigella sativa oil was later confirmed in PCOS patients exhibiting oligo-amenorrhea. Nigella oil increased menstrual regularity in PCOS patients by increasing LH, testosterone and insulin level in PCOS patients (93). Thymoquinone, an essential oil found in Nigella, showed its effectiveness against mifepristone induced PCOS in rats by decreasing autophagy through up-regulation of androgen receptors and proinflammatory cytokines, and up-regulation of aromatase enzyme. As this exercise has done because of a member with issue ---we can create a kit for it but none of studies suggest its overnight magic but time consuming and one needs to keep a mental frame of several months.
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