Introduction
Materials and Methods
Phenotype
Pathophysiology and Diagnosis
Sex Hormone Profile in PCOS
LH and FSH
-
Increase in LH secretion: in particular, there is an increase in the amplitude and frequency of the LH peaks in basal conditions and a hyper-response to the GnRH test. LH gonadotropin can be responsible for the hyperplasia of thecal ovary cells, an anatomopathological substrate that supports hyperandrogenism.
-
Normal or reduced levels of FSH: a hypo-functionality of the FSH cells of the ovarian granulosa axis is detected. The FSH low but steady levels continuously stimulate the growth of new follicles; these new follicles cannot reach complete maturation, undergoing atresia and not ovulation. These atretic follicles continue to enrich the ovarian stromal portion that secretes, under the stimulation of LH, a consistent number of androgens.
-
Ratio LH/FSH > 2.5: this typical pattern of gonadotropin secretion is the result either of an increased sensitivity of the pituitary gland to hypothalamic GnRH or an altered hypothalamic secretion of GnRH. It has been observed, indeed, that the pulsatile secretion of GnRH can modulate the synthesis of gonadotropins. In particular, a condition of pulsatile secretion of GnRH can stimulate the synthesis of LH, while a low pulsatile secretion would stimulate the synthesis of FSH. In women with PCOS, pulsatile secretion can induce the production of LH. The partial suppression of FSH, the greater sensitivity of this gonadotropin to the negative estrogen feedback, and the relative insensitivity to GnRH appear to be due to the inhibin, whose activity is increased in the ovarian follicles due to the excess of androgens [40, 41].
Estrogen and Progesterone
-
Peripheral conversion of androgens (aromatization of androgens in adipose tissue and skin)
-
Increased androgen-dependent aromatase activity of granulosa ovary cells
Hyperandrogenism
-
Cholesterol-desmolase (CYP11A1): responsible for converting cholesterol to pregnenolone
-
17α-Hydroxylase and 17,20-lyase: able to convert pregnenolone to 17-OH-pregnenolone and then to dehydroepiandrosterone (DHEA)
-
3-β-Hydroxydodehydrogenase: able to convert pregnenolone to progesterone, 17OH-pregnenolone to 17OH-progesterone, and DHEA to androstenedione
-
Total testosterone
-
Androstenedione
-
Dehydroepiandrosterone sulfate
-
Free androgens → calculated determination of free testosterone levels or through the free androgen index (FAI)
SHBG and AMH
PCOS and Insulin Resistance
Dietary Models and PCOS
Mediterranean Diet
Ketogenic Diet
Bariatric Surgery
Nutraceutical Supplementation
Probiotics, Prebiotics, and Synbiotics
First author, year of publication | Study type & design | Population | Results & major findings |
---|---|---|---|
Lei et al. 2020 | Systematic review and meta-analysis (just published and ongoing randomized controlled trials (RCTs) and human studies are included) | Adult women diagnosed as PCOS Ethnicity: regardless | Inositol and ALA combination is likely to act as a promising and safe therapy for PCOS women IR and oxidative stress status improvement |
Barrea et al. 2019 | Cross-sectional, observational study | 112 patients with PCOS, aged 18 to 40 years old (yo) Ethnicity: Caucasian | Association between the adherence to MD and the clinical severity of PCOS A role of PhA as a useful marker of the clinical severity of PCOS |
Mei et al. 2022 | Open-label, parallel-group randomized controlled trial | 72 patients with PCOS (aged 16 to 45 yo): 36 patients to low-fat (LF) diet group, 36 patients to MD/low carb (MD/LC) diet group Ethnicity: Asiatic (China) | Effectiveness of the LF and MED/LC dietary models in modifying anthropometric parameters, reproductive endocrine levels, IR levels, and lipid levels The MED/LC diet model was recommended for the treatment of overweight patients with PCOS |
Paoli et al. 2020 | 12 weeks, single-arm study (interventional) | 24 overweight women with PCOS, aged 18 to 45 yo, followed a Ketogenic diet (KD) for 12 weeks Ethnicity: not declared | KD as a possible therapeutic aid in PCOS |
Mavropoulos et al. 2005 | Pilot study (interventional) | 11 women with PCOS, aged 18 to 45 yo, BMI ≥ 27 kg/m2 Ethnicity: not declared | A LCKD led to significant reductions in weight, percent free testosterone, LH/FSH ratio, and fasting serum insulin in women with obesity and PCOS over a 6-month period |
Cincione 2021 | Interventional study | 17 overweight and obese women with PCOS, aged 18 to 45 yo, treated for 45 days with modified KD protocol, defined as “mixed ketogenic” Ethnicity: not declared | KD improves the anthropometric and many biochemical parameters (LH, FSH, SHBG, insulin sensitivity and HOMA index) and reduces androgenic production Improvement of the LH/FSH ratio |
Magagnini et al. 2022 | Retrospective study | 25 women, aged ≥ 18 yo, with PCOS and first-degree obesity, who underwent VLCKD-protocol (3 phases of VLCKD, 3 phases of low-calorie diet and 2 phases of maintenance diet that consisted of a balanced diet; each phase lasted 4 weeks) Ethnicity: Caucasian | Metabolic and ovulatory improvement is achieved in a relatively short time |
Ezzat et al. 2021 | Cohort study | 36 infertile women with PCOS, aged 22 to 40 yo, who underwent bariatric surgery Ethnicity: not declared | At 6 and 12 months post-bariatric surgery ↓ BMI, free, and total serum testosterone levels and free androgen index ↑ SHBG, menstrual cycle regularity |
Lili Hu et al. 2022 | Single-center, prospective, nonrandomized trial | 90 women with PCOS, aged 18 to 40 yo, BMI ≥ 27.5 kg/m2, divided in two groups: treated with drugs or bariatric surgery 12-month follow-up Ethnicity: not declared | Bariatric surgery should be the first-line treatment for patients with PCOS and obesity |
Masharani et al. 2010 | Interventional study | 6 non-obese women with PCOS, aged 23 to 24, were administered controlled-release ALA (CRLA) 600 mg twice daily for 16 weeks Ethnicity: not declared | ↑ insulin sensitivity ↓ triglyceride plasmatic levels ↓ LDL |
Genazzani et al. 2017 | Interventional study | 32 overweight/obese PCOS women, aged 23 to 26 yo, were administered alpha-lipoic acid (ALA) (400 mg) once a day for at least 3 months Ethnicity: not declared | ↓ insulin, glucose, BMI, and HOMA index, hyperinsulinemia, and insulin response to OGTT. The result of this study sustains the major role of ALA treatment on PCOS metabolic disease |
Cianci et al. 2015 | Prospective study, randomized controlled trial | 46 women with PCOS, aged 16 to 32 yo, were divided in two groups: study group (n. 26, 1000 mg D-chiro-inositol and 600 mg ALA daily) and control group (n. 20, untreated). Treatment was taken for 180 days Ethnicity: Caucasian | Clinical and metabolic aspects of women of study group improved compared to the control group. No statistically difference was observed in total cholesterol and triglycerides levels in both groups at follow-up |
Miao et al. 2020 | Meta-analysis | 11 studies involving 483 participants Ethnicity: regardless | No positive effect of vitamin D supplementation on BMI, dehydroepiandrosterone sulfate, triglyceride levels, or high-density lipoprotein-cholesterol Vitamin D supplementation reduced insulin resistance and hyperandrogenism, as well improved the lipid metabolism of patients with PCOS. Therefore, vitamin D should be considered as a treatment for PCOS |
Lindheim et al. 2017 | Pilot cohort study | 16S rRNA gene amplicon sequencing was performed on stool samples from 24 PCOS patients and 19 healthy controls, all aged ≥ 18 yo and pre-menopausal Ethnicity: not declared | PCOS patients have a lower diversity and an altered phylogenetic profile in their stool microbiome, which is associated with clinical parameters, compared to healthy group |
Torres et al. 2017 | Cohort study | 163 pre-menopausal women all aged ≥ 18 yo: healthy women (n. 48), women with polycystic ovarian morphology PCOM (n. 42), and women diagnosed with PCOS using the Rotterdam criteria (n. 73) Ethnicity: not declared | Lower α diversity in PCOS women vs healthy women. PCOM women showed an intermediate (between that of the other two groups) change in α diversity. Hyperandrogenism, total testosterone and hirsutism were negatively correlated with α diversity. Hyperandrogenism was also correlated with β diversity |
Cozzolino et al. 2020 | Systematic review and meta-analysis | 9 RCTs involving 587 PCOS women treated with probiotics or synbiotics (at least 8 weeks) or without therapy were included Ethnicity: regardless | In treated women: Improvement of metabolism, reduction of serum testosterone and systemic inflammation |
Therapy | Study model | Effects | References |
---|---|---|---|
Probiotic | Human | ↓BMI ↓glycaemia, ↓insulin, ↓ triglycerides, ↑ HDL Positive control of hormonal and inflammatory indicators | |
Prebiotic | Human | ↓glycaemia, ↓insulin, ↓ triglycerides, ↓ LDL ↓hyperandrogenism, ↓hirsutism, ↓menstrual cycle abnormalities Positive effects on immunomodulatory properties and metabolic markers | |
Synbiotic | Human | ↓BMI and body weight ↓glycaemia, ↓insulin, ↓HOMA-IR, ↓triglycerides Positive control on hormonal, metabolic, and inflammatory markers |