Effects of Combined Resveratrol and Myo-inositol on Altered Metabolic, Endocrine Parameters and Perceived Stress in Patients With Polycystic Ovarian Syndrome
Condition: PCOS
MeSH terms: Polycystic Ovary Syndrome
Study type: Interventional
Phase: Phase 2

Summary: 
      The investigators aim is to conduct a double blind randomized clinical trial, to study the
      effects of combined Resveratrol and Myo-Inositol on altered metabolic, endocrine parameters
      and perceived stress response in patients with Polycystic Ovary Syndrome (PCOS). Women
      diagnosed with PCOS, using criteria proposed in November 2015, by the American Association of
      Clinical Endocrinologists (AACE), American College of Endocrinology (ACE), and Androgen
      Excess and PCOS Society (AES) for PCOS should include two of the following three criteria:
      chronic an ovulation, hyperandrogenism (clinical/biologic), and polycystic ovaries. The
      investigators propose that PCOS women may have altered metabolic, endocrine levels and
      increased perceived stress response and combination therapy may have beneficial influences on
      these parameters in women diagnosed with PCOS.
    

Detailed description: 
      Polycystic ovarian syndrome (PCOS) is extremely prevalent and considered to be the most
      common heterogeneous endocrine disorder in reproductive age women. This affects up to 10-15%
      of women in reproductive age. PCOS is a multifaceted health issue characterized by chronic
      anovulation with excess ovarian activity, hyperandrogenism and polycystic ovaries. The most
      disappointment for women with PCOS is pregnancy loss.

      This endocrine disorder has some long term effects including cardiovascular diseases,
      metabolic and sexual dysfunction, depression and anxiety that effects the overall quality of
      life. Women with PCOS have a greater risk of developing hyperinsulinemia and insulin
      resistance and this explains the substantially increased prevalence of glucose intolerance in
      PCOS. Recent long-term follow up studies of the syndrome have shown that dyslipidemia and
      hyperlipidemia is a very common metabolic abnormality in these women. The key pathophysiology
      of PCOS is Insulin resistance, thus dyslipidemia in women may be constant with those found in
      an insulin resistant state. Low adiponectin levels in PCOS have been largely associated with
      obesity which is common among these patients. Serum adiponectin levels are associated with
      PCOS independently and are only explained by IR partly. An independent biomarker, adiponectin
      can be used for diagnosing PCOS in young and lean women or women with a family history of
      PCOS.

      Resveratrol (3,5,4-trihydroxy-trans-stilbene) belongs to polyphenols stilbene group found in
      grapes, peanuts, red wine and many medicinal plants. Studies have shown that patients treated
      with resveratrol have shown improve glucose homeostasis and reverse insulin resistance.
      Treatment with resveratrol improved the elevated number of atretic and secondary follicles
      and the decreased number of Graafian follicles in the PCOS group, which indicates the effect
      of the treatments on the maintenance of folliculogenesis. It has been reported to interact
      with multiple cell targets, but its major effects are brought about by the activation of
      SIRT1 (silent information regulator1).The SIRT1 is expressed in oocytes and human granulosa
      nuclei cells at multiple developmental stages of the follicles. It is also responsible for
      suppressing inflammation. Moreover, SIRT1 is also involved in protecting the oocytes from age
      dependent insufficiencies through oxidative stress.

      Myo-Inositol is a carbocyclic sugar, belongs to Inositol group and is an important component
      of structural lipids. Inositol's or its phosphates and the associated lipids are found in
      different fruits specially cantaloupe and oranges. It is the precursor of inositol
      triphosphate, acting as an intracellular second messenger and regulating a number of hormones
      such as thyroid-stimulating hormone, follicle-stimulating hormone (FSH) and insulin. One of
      the insulin-sensitizing compounds, Myo-Inositol is capable of restoring spontaneous ovarian
      activity, and consequently fertility, in most patients with PCOS. Inositol's improve the
      metabolic and endocrine parameters in young, overweight PCOS patients and regulate the
      monthly cycles. Treatment with inositol's in obese PCOS patients is also effective in
      reducing BMI. The decrease in BMI is without any lifestyle modification.

      PCOS is a systemic condition, an endocrinopathy whose etiology is still not understood,
      correct treatment regimens of PCOS will not only improve menstrual cycles of the patients but
      will also improve the metabolic or endocrinological parameters. PCOS sufferers are also known
      to have increased levels of perceived stress which will be considered in the study. Very
      little evidence is available on combination therapy for treatment of PCOS patients. In this
      study our goal will be to come up with a better treatment option to treat the disease
      effectively.

      Study Objectives:

      To investigate the effects of combined Resveratrol and Myo-Inositol treatment after 3 months
      on metabolic, endocrine alterations and perceived stress response in patients with PCOS.
    

Intervention name(s): Resveratrol (1000mg twice a day), Myoinositol 1000mg (Twice a day); Metformin (500 mg Twice a day), Pioglitazone (15 mg Twice a day)
Intervention type(s): Drug; Drug
Intervention description(s): 51 Patients with PCOS receiving Resveratrol and Myoinositol 1000mg and 1000mg BD daily respectively; 51 Patients with PCOS receiving Metformin and Pioglitazone 500 mg and 15 mg BD daily respectively
Other intervention name(s): Zolid Plus
Intervention MeSH terms: Inositol; Metformin; Pioglitazone; Resveratrol
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Outcomes Assessor)
Primary purpose: Treatment
Keywords: PCOS, Resveratrol and Myoinositol