Polycystic Ovary Syndrome

Valentin Borzan et al. (2023) · BMC endocrine disorders

This phase IV, double-blind randomized controlled trial with 180 participants (ProPCO-RCT) explored whether a multi-strain probiotic supplement can improve hormone and metabolic markers in women with Polycystic Ovary Syndrome (PCOS), a condition affecting up to one in five women that combines irregular periods, excess androgen (male hormone) activity, and polycystic ovaries. The trial's premise builds on prior findings that women with PCOS have a less diverse gut microbiome, which past research has linked to higher testosterone and greater insulin resistance. The study also examines equol, a compound gut bacteria make from soy isoflavones that has anti-androgenic properties, framing the gut microbiome as a possible lever on PCOS hormone levels. Participants (ages 18-45, meeting standard Rotterdam PCOS diagnostic criteria) were split into three groups of 60: a seven-strain probiotic sachet, a matching placebo, or open-label metformin (a standard PCOS drug), each taken daily for six months. The probiotic-versus-placebo comparison was blinded and allocation-concealed; the metformin group was not blinded. Measurements included blood hormone panels, an oral glucose tolerance test, a hirsutism (excess hair growth) score, body measurements, gut permeability and stool-microbiome testing (via genetic sequencing), and symptom and mood questionnaires, taken at the start and repeated at six months. As a protocol paper, this publication describes the trial's design rather than its findings — the primary comparison (change in free testosterone, probiotic versus placebo) had not yet been unblinded or analyzed at the time of publication. The one concrete number reported comes from the research group's earlier, smaller pilot study: 10 women taking the same probiotic for three months saw their free testosterone drop by a median of 0.3 pg/ml (range 1.7 down to 2.5 up), a result the team used to calculate that 60 participants per group would give the trial 80% power to detect a larger, expected 0.6 pg/ml reduction. The full trial adds metformin as a benchmark and follows participants for twice as long as most prior probiotic-PCOS studies the authors cite, several of which reported androgen and metabolic improvements with about 60 participants total. Because the results are not yet in, the paper's value lies in its design: registered with clinical trial authorities (ClinicalTrials.gov NCT04593459), ethics-approved, and built to isolate a probiotic's effect from both an inert placebo and an established drug. The authors describe it as the first trial to test a probiotic against both comparators in PCOS. The protocol also flags a limitation the authors state plainly: recruitment began before the COVID-19 pandemic, and the trial's long six-month intervention window may make some participants unable to fully follow the schedule, which is why the statistical plan pre-specifies analyzing everyone as originally assigned. Readers looking for evidence of probiotic effectiveness in PCOS will need the trial's later results publication, not this one.

Béla E Tóth et al. (2025) · Nutrients

This prospective, double-blind, two-phase randomized controlled trial with 84 analyzed participants explored whether weekly high-dose vitamin D3 (a fat-soluble vitamin that also acts on hormone-producing tissue through its receptor, VDR) could improve ovarian function in polycystic ovary syndrome (PCOS), a common hormonal condition marked by irregular or absent ovulation (the release of an egg), elevated androgens ("male-pattern" hormones such as testosterone), and, frequently, vitamin D deficiency. Earlier studies had linked low vitamin D status to PCOS but disagreed on whether raising vitamin D levels actually changes ovulation, cycle length, or hormone levels. Conducted at eight Hungarian clinical sites between 2016 and 2020, the trial randomized women meeting Rotterdam PCOS criteria to one of two oral regimens: 30,000 IU of vitamin D3 weekly, plus calcium, either immediately for 24 continuous weeks or only after a 12-week placebo lead-in period. Ovarian morphology was tracked with transvaginal ultrasound, and ovulation was confirmed through luteal-phase progesterone testing (values above 10 ng/mL) rather than self-report alone, at baseline and after 12 and 24 weeks of treatment. After 12 weeks of vitamin D3, average menstrual cycle length dropped by 11.7 days (p = 0.032, meaning this reduction was unlikely to be due to chance), and confirmed ovulation rose from about 40% to 59-65% of participants (p = 0.044). Serum vitamin D rose to a mean of 45.1 ng/mL (p < 0.001), confirming adequate repletion. Testosterone fell significantly only in two specific subgroups: women with elevated androstenedione ("hyperandrogenic," p = 0.047) and those with a higher LH/FSH hormone ratio (p = 0.0082) — a pattern the authors connect to differing PCOS phenotypes rather than one uniform hormonal response. Ultrasound-confirmed normal ovarian appearance was reached in 20% of participants after 12 weeks (p < 0.05 versus placebo), improving further by 24 weeks, though that later difference was not statistically significant. No serious treatment-related side effects were reported, and vitamin D levels stayed within the study's predefined safety range throughout. The authors suggest vitamin D3 could serve as a standalone or add-on approach for PCOS, particularly for hyperandrogenic phenotypes and those with a higher LH/FSH ratio. They identify the trial's sample size (84 analyzed participants), the relatively short 12-plus-12-week duration, and luteal-phase-only hormone sampling as limitations restricting broader conclusions, and note that longer trials with serial ultrasound monitoring and larger, phenotype-defined groups are needed to confirm these phenotype-specific patterns and to establish how long the ovulatory and cycle-length benefits persist after treatment ends.

Zahra Najdgholami et al. (2025) · Frontiers in endocrinology

This 12-week open-label randomized controlled trial with 70 women explored whether daily flaxseed intake could shift reproductive hormone patterns in polycystic ovary syndrome (PCOS), a common endocrine condition affecting 6 to 15 percent of women of reproductive age. PCOS involves hyperandrogenism (elevated androgen hormones) and disrupted ovulation, often accompanied by a low or borderline follicle-stimulating hormone (FSH) that limits egg follicles from fully maturing. Flaxseed is a plant-based food rich in phytoestrogenic lignans (plant compounds structurally similar to estrogen) and omega-3 fatty acids, both proposed to influence the hormone pathways governing follicle development and gonadotropin balance. Seventy women diagnosed with PCOS at a clinic in Ahvaz, Iran were randomly assigned to 12 weeks of either 30 grams of daily milled flaxseed added to salads, yogurt, or cold drinks, combined with standard diet and exercise guidance, or the same lifestyle guidance without flaxseed. Blood tests measuring FSH, luteinizing hormone (LH), anti-Mullerian hormone, estradiol, DHEAS, and androstenedione were drawn at baseline and after 12 weeks using enzyme immunoassays and chemiluminescent assays, timed to each participant's menstrual cycle phase where applicable. FSH rose significantly more in the flaxseed group than in controls (treatment effect 0.87, 95% CI 0.086-1.75, p=0.027), meaning flaxseed users saw a measurably larger increase in this follicle-stimulating hormone than those on lifestyle changes alone. The ratio of LH to FSH also dropped significantly with flaxseed (treatment effect -0.341, 95% CI -0.63 to -0.08, p=0.031), a lower ratio pointing toward more balanced gonadotropin secretion, since an elevated LH/FSH ratio is a hallmark of PCOS. No significant between-group changes appeared for AMH, LH alone, estradiol, DHEAS, or androstenedione, indicating flaxseed's measured effect was specific to FSH and its ratio to LH rather than the broader hormone panel. Weight, BMI, lipids, and blood sugar stayed similar between groups, and no adverse events were reported, suggesting the 30-gram daily dose was well tolerated over the 12 weeks. The authors propose that flaxseed's omega-3 fatty acids and lignans may support follicle-stimulating hormone receptor activity and gonadotropin regulation, though this mechanism was not directly tested in the trial. The open-label design, unavoidable for a dietary intervention, the single-center setting, and the absence of testosterone and insulin measurements limit how broadly the results extend. The authors identify larger, longer randomized trials incorporating androgen and insulin outcomes as the needed next step for confirming flaxseed's role in PCOS management.

Hadis Hooshmandi et al. (2024) · Journal of ovarian research

This 8-week randomized, double-blind, placebo-controlled trial with 66 women explored whether licorice (Glycyrrhiza glabra) root extract could ease some of the metabolic burden of polycystic ovary syndrome (PCOS), a hormonal condition marked by irregular ovulation, elevated androgen levels, and polycystic ovaries on ultrasound. PCOS frequently occurs alongside obesity and insulin resistance, the body's reduced response to insulin, which raises blood sugar and makes weight loss harder to achieve. The trial paired licorice extract with a calorie-restricted diet to test whether the herb added benefit beyond diet alone. Seventy-two overweight or obese women with PCOS, ages 18 to 45, at a clinic in Yazd, Iran, were randomly assigned to 1,500 mg of standardized licorice extract daily, taken as three capsules before meals, or a matching placebo, both alongside the same reduced-calorie diet, for 8 weeks. Sixty-six women completed the study. Body composition was measured with a bioelectrical impedance analyzer, and blood tests tracked fasting glucose, insulin, and cholesterol levels before and after treatment. Women taking licorice lost more weight than those on diet alone (82.60 kg versus 86.09 kg, a statistically significant difference at p<0.001) and showed larger drops in body mass index and body fat percentage. Their fasting blood sugar (74.0 versus 94.0 mg/dl), insulin (6.68 versus 11.06 µIU/ml), and an insulin-resistance score called HOMA-IR (1.23 versus 2.55) all improved significantly more than in the placebo group (p<0.001), as did triglycerides and total and LDL cholesterol (all lower with licorice) and HDL cholesterol (higher, the more favorable direction) (p between <0.001 and 0.01). A separate measure of insulin-producing capacity, HOMA-B, improved within the licorice group and looked better than placebo before statistical adjustment, but that edge disappeared once the analysis accounted for baseline differences and other factors, a reminder that not every raw difference holds up under closer scrutiny. Diet and activity levels were identical between the two groups throughout the study, and the low-calorie diet alone produced no measurable change in any of these markers over the 8 weeks. The authors propose that licorice's compounds act on fat metabolism, insulin signaling, and cholesterol handling through several biological pathways, though those pathways were not directly measured in this trial. The study ran for only 8 weeks, did not test licorice without the accompanying diet, and relied on 24-hour dietary recall, a self-reported method that can be imprecise. Longer trials isolating licorice's own effect and testing its proposed mechanisms, in more diverse populations than this single-center Iranian cohort, are needed to confirm these results.

Aliasghar Manouchehri et al. (2023) · JBRA assisted reproduction

Polycystic ovary syndrome (PCOS) is one of the most common hormone-related conditions affecting women of reproductive age, estimated to affect 4-25% of women depending on how it is diagnosed (14.6% in Iran). Beyond irregular periods and fertility struggles, PCOS often comes with insulin resistance, weight gain, acne, excess hair growth, and long-term metabolic risk. Because standard medications can carry side effects, researchers have looked to medicinal plants as gentler options. This review pulls together what is known about nine herbs -- from aloe vera to flax -- and how each is thought to act on the hormonal and metabolic disruptions behind PCOS. Unlike a systematic review with a registered search protocol, this is a narrative synthesis: the authors describe the proposed mechanism of each of nine plants -- aloe vera, chamomile, chaste tree, cinnamon, ginseng, stachys, fennel, liquorice, and flax -- based mainly on animal and laboratory studies rather than human clinical trials. Each plant's key active compound and hypothesized mechanism of action are summarized in a comparison table, covering effects on hormone levels, ovarian tissue, insulin sensitivity, and inflammation. Each herb is proposed to work differently. Cinnamon appears to improve insulin sensitivity and lower blood sugar and lipids by affecting insulin-receptor signaling. Chaste tree and fennel are proposed to shift the balance of reproductive hormones (chaste tree lowering testosterone, fennel raising progesterone and thickening the uterine lining). Flax's lignans are linked to lower androgen levels and less excess hair growth (hirsutism), while stachys is proposed to ease abnormal uterine bleeding by damping estrogen receptor activity. Chamomile and aloe vera are described as supportive of ovarian tissue and follicle development, and ginseng and liquorice are framed around broader immune and metabolic support. Importantly, the review does not report clinical trial results, statistics, or human outcome data for any of these plants -- the mechanisms described come mainly from animal models and lab studies, not from testing in women with PCOS. The authors see herbal medicine as a promising, low-side-effect complement to PCOS care, working mainly through immune support and cycle regulation rather than direct hormone replacement -- but they are careful to say more research time is needed. Because this is a synthesis of mostly preclinical and mechanistic findings, none of these nine plants can be considered proven PCOS treatments; each is better read as a lead for future controlled human trials than as an established remedy to try in place of medical care.