PCOS
Everything in the library studied for it, medical and holistic together. Within each kind, what was shown to help comes first, strongest evidence first. What was tested and not shown to help stays on the list.
Strong several reviews agree · Moderate one review or consistent trials · Limited one or a few small studies · Untested no study in people, listed with what it rests on
Medication
Live birth in PCOS: letrozole compared with clomiphene
Shown to raise live births in women with PCOS against clomiphene, 27.5% against 19.1% in the largest trial, about one extra birth per 10 women treated.
Compared with clomiphene or other selective estrogen receptor modulators [3]; clomiphene [4][5]
The numbers and sources
- How common
- Very common: more than 1 in 10 people.
- Effect
- Across 11 trials (2,060 women), live births after ovulation induction and timed intercourse were higher with letrozole than with selective estrogen receptor modulators such as clomiphene (OR 1.72, 95% CI 1.40 to 2.11, I² 0%), with a number needed to treat of 10. Where 20% of women would have a live birth on clomiphene, 27% to 35% would on letrozole [3]. A second meta-analysis, with 8 trials reporting live birth, found a risk ratio of 1.49 (95% CI 1.27 to 1.74) [4]. In the PPCOS II trial, 103 of 374 women (27.5%) on letrozole and 72 of 376 (19.1%) on clomiphene had a live birth over up to five cycles (rate ratio 1.44, 95% CI 1.10 to 1.87) [5].
- Population
- 2,060 women with anovulatory PCOS in 11 trials, within a review of 41 trials and 6,522 women [3]. 3,952 women with PCOS in 29 trials [4]. 750 women aged 18 to 40 with PCOS, double-blind, at US centers [5].
- Sources
- [3], [4], [5]
- Caveats
- The Cochrane review set aside six earlier trials over concerns about the validity of their data, and a funnel plot showed mild asymmetry suggesting some trials favoring the comparison drugs may be missing [3]. The authors of the second review describe the quality of the evidence as mixed [4].
Ovulation and pregnancy in PCOS: letrozole compared with clomiphene
Shown to raise ovulation and pregnancy rates in women with PCOS against clomiphene. In the largest trial, 61.7% of letrozole cycles and 48.3% of clomiphene cycles were ovulatory.
Compared with clomiphene [4][5][6]; clomiphene or other selective estrogen receptor modulators [3]
The numbers and sources
- How common
- Very common: more than 1 in 10 people.
- Effect
- Ovulation was more frequent with letrozole across 22 trials (RR 1.14, 95% CI 1.06 to 1.21) [4] and across 50 trials (RR 1.20, 95% CI 1.13 to 1.26), and pregnancy across 50 trials (RR 1.44, 95% CI 1.28 to 1.62). The endometrium was thicker on letrozole (SMD 0.89) and fewer follicles developed (SMD -0.56) [6]. In PPCOS II, 834 of 1,352 letrozole cycles (61.7%) and 688 of 1,425 clomiphene cycles (48.3%) were ovulatory [5]. Clinical pregnancy was higher with letrozole across 23 trials (OR 1.69, 95% CI 1.45 to 1.98): where 24% would conceive on clomiphene, 32% to 39% would on letrozole [3].
- Population
- Women with PCOS in 22 trials [4] and 50 trials [6]. 750 women with PCOS [5]. 3,321 women in 23 trials [3].
- Sources
- [3], [4], [5], [6]
- Caveats
- Heterogeneity was moderate to high in the 50-trial analysis (I² 54% for ovulation, 66% for pregnancy, 98% for endometrial thickness) [6]. Ovulation and pregnancy are steps toward a live birth, which is reported in the block above.
Ovulation and pregnancy in PCOS
Shown to raise ovulation and clinical pregnancy rates against placebo in women with PCOS. The rise in live births rests on low-quality evidence.
Compared with placebo or no treatment [30][31]; clomiphene citrate [30]
The numbers and sources
- Effect
- Against placebo or no treatment, metformin raised ovulation (OR 2.64, 95% CI 1.85 to 3.75, 13 studies, 684 women, low quality) and clinical pregnancy (OR 1.98, 95% CI 1.47 to 2.65, 11 studies, 1,213 women, moderate quality). Live birth rose from 19% on placebo to between 19% and 37% on metformin (OR 1.59, 95% CI 1.00 to 2.51, 4 studies, 435 women, low quality). The effect on miscarriage was uncertain (OR 1.08, 95% CI 0.50 to 2.35). Against clomiphene citrate, women with obesity had fewer live births on metformin (OR 0.30, 95% CI 0.17 to 0.52, 2 studies, 500 women) [30]. A second review found higher odds of clinical pregnancy on metformin than placebo (OR 3.00, 95% CI 1.95 to 4.59) [31].
- Population
- 41 RCTs with 4,552 women with PCOS and subfertility [30]; 24 RCTs with 564 women with PCOS given metformin [31].
- Sources
- [30], [31]
- Caveats
- Evidence quality ranged from very low to moderate, limited by risk of bias, imprecision and inconsistency. Results differed by body mass index [30]. The second review's abstract does not say how many trials reported pregnancy [31].
Weight in PCOS
Shown to lower BMI slightly more than placebo in women with PCOS, by about 0.5 to 0.8 kg/m2, or about 3 kg of body weight.
Compared with placebo [34][31]; lifestyle change with or without placebo [33]
The numbers and sources
- Effect
- Against placebo, metformin with or without lifestyle change lowered BMI by 0.53 kg/m2 more (95% CI 0.12 to 0.95, moderate certainty) and waist-hip ratio by 0.02 more (low certainty) [34]. A second review found 3.13 kg more weight lost (95% CI 0.93 to 5.33) and BMI 0.82 kg/m2 lower (95% CI 0.41 to 1.22) than placebo [31]. Lifestyle change plus metformin lowered BMI 0.73 kg/m2 more than lifestyle change with or without placebo over 6 months (95% CI 0.32 to 1.14). Metformin alone gave similar weight and BMI to lifestyle change [33].
- Population
- RCTs in women with PCOS published through July 2022 [34]; 24 RCTs with 564 women given metformin [31]; 12 RCTs with 608 women [33].
- Sources
- [34], [31], [33]
- Caveats
- The differences are small. Trials were small and short [33]. The 2023 review was written to inform the international PCOS guideline [34].
Insulin resistance and blood sugar in PCOS
Shown to lower insulin resistance and fasting glucose slightly against placebo in women with PCOS. Added to lifestyle change, one review found no extra effect.
Compared with placebo [34][31]; lifestyle change with or without placebo [33]; combined oral contraceptive pills [35]
The numbers and sources
- Effect
- Against placebo, metformin lowered HOMA-IR by 0.50 (95% CI 0.09 to 0.91) and fasting glucose by 0.13 mmol/L (95% CI 0.07 to 0.19), both moderate certainty [34]. A second review also found lower fasting glucose than placebo (SMD -0.23, 95% CI -0.40 to -0.06) [31]. Lifestyle change plus metformin did not differ from lifestyle change with or without placebo on surrogate markers of insulin resistance or fasting glucose after 6 months [33]. Against combined oral contraceptive pills, metformin lowered insulin by 27.12 pmol/L (95% CI 13.59 to 40.65) [35].
- Population
- RCTs in women with PCOS published through July 2022 [34]; 24 RCTs with 564 women given metformin [31]; 12 RCTs with 608 women [33]; 36 RCTs in women with PCOS [35].
- Sources
- [34], [31], [33], [35]
- Caveats
- The changes are small. The add-on comparison rests on small, short trials [33].
Menstrual cycles in PCOS
Shown to make periods more frequent in women with PCOS, against placebo and when added to lifestyle change, on low-quality evidence.
Compared with placebo or no treatment [32]; lifestyle change with or without placebo [33]
The numbers and sources
- Effect
- Against placebo or no treatment, metformin raised menstrual frequency (OR 1.72, 95% CI 1.14 to 2.61, 7 studies, 427 women, low-quality evidence) [32]. Lifestyle change plus metformin gave about one more menstrual cycle over 6 months than lifestyle change with or without placebo (MD 1.06, 95% CI 0.30 to 1.82) [33].
- Population
- 48 RCTs with 4,451 women with PCOS and infrequent or absent ovulation, 42 of them on metformin [32]; 12 RCTs with 608 women with PCOS [33].
- Sources
- [32], [33]
- Caveats
- Each comparison rests on one review. Heterogeneity was moderate (I² 54%) [32]. Trials were small and short, with risk of bias [33].
Irregular cycles in PCOS
Limited evidence: one review found cycles became regular on the pill in women with PCOS, against none without medical treatment, at low certainty.
Compared with no medical treatment, placebo or lifestyle change [35]
The numbers and sources
- Effect
- Cycle regularity improved in 100% on the combined pill and 0% without medical treatment, at low certainty. Hirsutism and BMI did not differ from placebo or lifestyle change, weight was 8.0 kg lower than with no treatment, and quality of life was slightly higher, all at very low certainty [35].
- Population
- Women with PCOS in 4 RCTs, none of which could be pooled [35].
- Sources
- [35]
- Caveats
- Only 4 small trials. The review was written for the 2023 international PCOS guideline, whose authors note that pill use in PCOS rests mostly on evidence from the general population [35].
Pregnancy in PCOS: clomiphene compared with placebo
Limited evidence: clomiphene raised clinical pregnancy against placebo in women with PCOS, in 3 small trials of 133 women. No placebo-controlled trial reported live birth.
Compared with placebo [7]; gonadotropin injections [7]
The numbers and sources
- Effect
- Clomiphene was linked to more clinical pregnancies than placebo (OR 5.91, 95% CI 1.77 to 19.68). If 5% conceived on placebo, between 8% and 50% would on clomiphene. No live birth, miscarriage, multiple pregnancy or ovarian hyperstimulation data were reported against placebo. Against a gonadotropin, clomiphene was linked to fewer pregnancies, ongoing pregnancies and live births, in limited evidence [7].
- Population
- 133 women in 3 trials, within a review of 28 trials and 3,377 women with anovulatory subfertility [7].
- Sources
- [7]
- Caveats
- The reviewers rated the evidence low to very low in quality, mainly for imprecision and poor reporting, and advise caution because of low event rates [7].
Hirsutism and cycles in PCOS
Small open-label trials in women with PCOS found hirsutism scores fell more with spironolactone than with metformin, and more with the two combined than with either alone.
Compared with metformin 1,000 mg a day [22][23]; metformin 1,700 mg a day alone [24]; spironolactone alone [23]
The numbers and sources
- Effect
- Over 6 months, the Ferriman-Gallwey hirsutism score fell from 12.9 to 8.7 on spironolactone 50 mg a day and from 12.5 to 10.0 on metformin. Menstrual cycles rose from 6.6 to 10.2 a year on spironolactone and from 5.7 to 9.1 on metformin (P = 0.0037). Testosterone fell in both groups, and weight and blood pressure did not change [22]. In a three-arm trial, spironolactone 50 mg plus metformin raised cycles a year and lowered hirsutism score, total testosterone and glucose and insulin area under the curve more than either drug alone (P < .05) [23]. Adding spironolactone 25 mg to metformin lowered the hirsutism score more than metformin alone (P < 0.001), while regular menses returned in 68% on the combination and 82% on metformin alone [24].
- Population
- 82 adolescent and young women with PCOS randomized, 69 completing, mean age 22.6 [22]; 198 women with PCOS randomized, 169 completing [23]; 56 women with PCOS [24].
- Sources
- [22], [23], [24]
- Caveats
- All three trials were open-label, small and lasted 6 months, with no placebo group. Two came from the same research group [22][23]. Not an FDA-approved use [3].
Gut side effects in women with PCOS
Shown to raise gut side effects in women with PCOS, from 10% on placebo to between 22% and 40% on metformin.
The numbers and sources
- How common
- Very common: more than 1 in 10 people.
- Effect
- Against placebo, gastrointestinal side effects rose from 10% to between 22% and 40% (OR 4.00, 95% CI 2.63 to 6.09, 7 studies, 713 women, moderate quality) [30]. A second review found more mild gastrointestinal adverse effects on metformin than placebo (OR 7.67, 95% CI 2.74 to 21.46) [34]. Against combined oral contraceptive pills, metformin may raise severe gastrointestinal adverse events (Peto OR 6.42, 95% CI 2.98 to 13.84, 11 RCTs, 602 women) and lower other severe adverse events (Peto OR 0.20, 95% CI 0.09 to 0.44) [36].
- Population
- Women with PCOS and subfertility [30]; RCTs in women with PCOS published through July 2022 [34]; 44 RCTs with 2,253 women and adolescents with PCOS [36].
- Sources
- [30], [34], [36]
- Caveats
- The comparison with the pill rests on low-quality evidence [36].
Excess hair and androgens in PCOS
Mixed results: against metformin, hair growth improved about the same in one review and more on the pill in overweight women in another.
Compared with metformin [36][37]; metformin combined with the pill [36][37]; placebo or lifestyle change [35]; other combined pills [38]
The numbers and sources
- Effect
- Against metformin, hirsutism did not differ, while free androgen index was 7.08 lower, SHBG 118.61 nmol/L higher and testosterone 0.48 nmol/L lower on the pill. Adding metformin to the pill lowered free androgen index and raised SHBG further [36]. A Cochrane review found metformin may improve hirsutism less than the pill in women with BMI 25 to 30 (MD 1.92, 95% CI 1.21 to 2.64), with an uncertain difference at other BMIs, and the pill plus metformin improved hirsutism more than the pill alone [37]. Hirsutism did not differ from placebo or lifestyle change, at very low certainty [35]. Pills with cyproterone acetate lowered hirsutism and testosterone (MD 0.38 nmol/L) more than conventional pills, and high and low estrogen doses did not differ [38].
- Population
- 36 RCTs in women with PCOS [36]; 44 RCTs with 2,253 women and adolescents with PCOS [37]; 4 RCTs [35]; 19 RCTs comparing two pills [38].
- Sources
- [36], [37], [35], [38]
- Caveats
- Cochrane evidence quality was very low to low [37]. The guideline reviewers noted the higher clot risk of cyproterone acetate pills in the general population [38].
Excess hair and androgens in PCOS
Mixed results: against the pill, hair growth improved about the same in one review and less in overweight women in another. Metformin lowered testosterone against placebo.
Compared with combined oral contraceptive pills [35][36]; metformin combined with the pill [36]; placebo [31]; lifestyle change with or without placebo [33]
The numbers and sources
- Effect
- Hirsutism did not differ between metformin and combined oral contraceptive pills, while free androgen index was 7.08 higher, SHBG 118.61 nmol/L lower and testosterone 0.48 nmol/L higher on metformin than on the pill [35]. In a Cochrane review, metformin may improve hirsutism less than the pill in women with BMI 25 to 30 (MD 1.92, 95% CI 1.21 to 2.64, 5 RCTs, 254 women), with an uncertain difference at other BMIs. Metformin alone and the pill alone each improved hirsutism less than the two combined [36]. Against placebo, metformin lowered total testosterone (SMD -0.33, 95% CI -0.49 to -0.17) [31]. Lifestyle change plus metformin did not differ from lifestyle change on clinical or biochemical hyperandrogenism, while metformin alone gave lower testosterone than lifestyle change [33].
- Population
- 36 RCTs in women with PCOS [35]; 44 RCTs with 2,253 women and adolescents with PCOS [36]; 24 RCTs with 564 women given metformin [31]; 12 RCTs with 608 women [33].
- Sources
- [35], [36], [31], [33]
- Caveats
- Cochrane evidence quality was very low to low [36]. Hirsutism scales and trial lengths varied.
PCOS: letrozole compared with ovarian drilling surgery
Limited evidence: in one trial of 141 women with PCOS, live births did not differ significantly between letrozole and laparoscopic ovarian drilling.
Compared with laparoscopic ovarian drilling [3]
The numbers and sources
- Effect
- Live birth OR 2.07 (95% CI 0.99 to 4.32). Where 22% would have a live birth after drilling, 24% to 47% would on letrozole. Clinical pregnancy did not differ significantly across 3 trials (OR 1.47, 95% CI 0.95 to 2.28) [3].
- Population
- 141 women in 1 trial for live birth, 367 women in 3 trials for pregnancy [3].
- Sources
- [3]
- Caveats
- The reviewers rated the live birth evidence very low in certainty and the pregnancy evidence low [3].
Supplements
Insulin resistance
Shown to lower HOMA-IR and fasting insulin slightly in overweight adults and women with PCOS. Fasting glucose and HbA1c did not change significantly.
The numbers and sources
- Effect
- In 20 trials in overweight and obese adults, HOMA-IR fell 0.26 (95% CI -0.48 to -0.03) and fasting insulin 12.55 pmol/L (95% CI -23.62 to -1.47). Fasting glucose (-1.60 mg/dL, 95% CI -3.28 to 0.07) and HbA1c (-0.05 points, 95% CI -0.19 to 0.07) did not change significantly [6]. In 10 RCTs in 683 women with polycystic ovary syndrome, chromium lowered fasting insulin (p 0.01) and raised the insulin sensitivity index QUICKI (p 0.02) against placebo. Against metformin, HOMA-IR fell more on chromium (p < 0.00001) [7].
- Population
- Overweight and obese adults, with trial sizes of 1 to 137 [6]; women with polycystic ovary syndrome [7].
- Sources
- [6], [7]
- Caveats
- The two reviews studied different populations. The PCOS abstract gives p-values without effect sizes [7]. The overweight analysis abstract calls the fasting glucose fall significant though its interval crosses zero [6]. In 2005 FDA ranked the evidence for chromium picolinate and insulin resistance at its lowest level for a qualified claim [5].
Menstrual cycles and ovulation in PCOS
Shown to make a regular cycle about 1.8 times as likely as placebo in women with PCOS. The guideline review called the evidence limited.
The numbers and sources
- Effect
- A regular cycle was 1.79 times as likely on inositol as on placebo (95% CI 1.13 to 2.85), and results did not differ from metformin [1]. In an earlier analysis, ovulation rate (RR 2.3, 95% CI 1.1 to 4.7) and cycle frequency (RR 6.8, 95% CI 2.8 to 16.6) were higher than placebo [2]. A review for the 2023 international PCOS guideline found possible ovulation benefits for D-chiro-inositol and called the overall evidence limited and inconclusive [3].
- Population
- 1,691 women in 26 trials [1]; 601 women in 10 trials [2]; 2,230 women in 30 trials [3].
- Sources
- [1], [2], [3]
- Caveats
- Sources disagree on certainty. Pregnancy rates came from single trials, and no trial reported live births or miscarriage [2]. Ovulation heterogeneity was high (I² 75%) [2].
Hormones and blood sugar in PCOS
Shown to lower free and total testosterone and glucose and raise SHBG in women with PCOS. Metformin did better on hirsutism.
The numbers and sources
- Effect
- Against placebo, inositol lowered BMI (MD -0.45), free testosterone (MD -0.41), total testosterone (MD -20.4) and glucose (MD -3.14), and raised sex-hormone-binding globulin (MD 32.1) [1]. The guideline review found benefits for some metabolic measures and none for others. Metformin did better on waist-hip ratio and hirsutism [3].
- Population
- 1,691 women in 26 trials [1]; 2,230 women in 30 trials [3].
- Sources
- [1], [3]
- Caveats
- Units are as reported in the abstract. The guideline review rated BMI evidence very uncertain [3].
Polycystic ovary syndrome
Shown to raise progesterone and endometrial thickness in women with PCOS. These are hormone and ultrasound measures, not pregnancy rates.
The numbers and sources
- Effect
- Across 22 studies (2,515 women), NAC was associated with higher progesterone (SMD 0.95, 95% CI 0.13 to 1.77) and thicker endometrium (SMD 0.58, 95% CI 0.10 to 1.06) than placebo and other drugs. Estradiol, SHBG and FSH did not differ [7].
- Population
- Women with PCOS, compared with placebo, metformin or clomiphene [7].
- Sources
- [7]
- Caveats
- Hormone and ultrasound measures, not pregnancy or live birth rates. Comparators were mixed.
Ovulation, pregnancy and cycles in PCOS
Shown in one review to raise ovulation and pregnancy rates, and in another to make cycles more regular, in women with PCOS given vitamin D alongside other treatment.
Compared with placebo, metformin, short-acting contraceptives, ovulation drugs or assisted reproduction without vitamin D [69]; controls the source abstract does not describe [70]
The numbers and sources
- Effect
- Across 20 RCTs (1,961 women), adding vitamin D raised pregnancy rate (RR 1.44, 95% CI 1.28 to 1.62) and ovulation rate (RR 1.42, 95% CI 1.14 to 1.78) and lowered early miscarriage (RR 0.44, 95% CI 0.30 to 0.66) [69]. Across 12 studies (849 women), cycles became more regular (RR 1.35, 95% CI 1.18 to 1.54), with significant effects only above 4,000 IU a day, beyond 8 weeks, or with other supplements. LH fell (SMD -0.41) and FSH did not change [70].
- Population
- Women with PCOS seeking pregnancy, mean age about 29, most with low vitamin D at baseline [69]; 849 women with PCOS [70].
- Sources
- [69], [70]
- Caveats
- 12 of the 20 trials in [69] were published in Chinese. In [69], vitamin D was added on top of the control treatment, so it measures an add-on effect. Each outcome rests on one review.
Blood sugar and insulin in PCOS
Shown in one review to lower fasting glucose and insulin slightly against placebo in women with PCOS. An earlier review found changes mainly with other nutrients.
Compared with placebo [71][72]
The numbers and sources
- Effect
- Across 13 RCTs (691 women), vitamin D lowered fasting glucose by 2.91 mg/dL (95% CI 1.04 to 4.78) and insulin by 1.98 µIU/mL (95% CI 0.64 to 3.32) more than placebo, with lower triglycerides, total cholesterol and LDL cholesterol [71]. An earlier review of 11 RCTs (601 women) found lower fasting glucose and HOMA-IR when vitamin D was given with other micronutrients, and lower HOMA-IR at doses under 4,000 IU a day [72].
- Population
- Women aged 18 and older with PCOS in 13 RCTs [71]; 601 women with PCOS in 11 RCTs [72].
- Sources
- [71], [72]
- Caveats
- The changes are small. The earlier review's abstract gives no effect size and does not report a significant effect for vitamin D alone at all doses [72].
Inflammation markers
One small trial found 1,000 mg a day lowered IL-6 in 60 women with PCOS. Trials of other inflammation markers conflicted.
The numbers and sources
- Effect
- In 60 women with polycystic ovary syndrome, 1,000 mg a day of oil for 12 weeks lowered serum IL-6 against placebo (adjusted mean difference -4.21, 95% CI -6.34 to -2.08) and fasting glucose by 8.16 mg/dL. Fasting insulin and HOMA-IR did not differ [9]. A review of 4 human trials found conflicting results for the adhesion molecules VCAM-1 and ICAM-1 [10].
- Population
- 60 women with PCOS [9]. Patients with coronary artery disease, type 2 diabetes, Hashimoto's thyroiditis or cardiovascular risk factors [10].
- Sources
- [9], [10]
- Caveats
- One small trial for IL-6 [9]. The adhesion molecule review also included 15 animal and in vitro studies, which are not counted here [10].
Fertility treatment in PCOS
Mixed results: one review found higher clinical pregnancy rates in women with PCOS in fertility treatment, and a larger review found no effect.
The numbers and sources
- Effect
- In 17 intervention studies of women with PCOS undergoing assisted reproduction, myo-inositol or D-chiro-inositol raised the clinical pregnancy rate (RR 1.64, 95% CI 1.25 to 2.15) and top-grade embryos (RR 1.12), and lowered antral follicle count and anti-Mullerian hormone [8]. In 11 studies (981 women undergoing IVF), myo-inositol raised the mature (MII) oocyte rate (OR 1.55, 95% CI 1.04 to 2.31) and the fertilization rate (OR 1.62, 95% CI 1.21 to 2.16). The MII oocyte rate did not rise in poor responders [9]. A 2026 meta-analysis of 39 studies found fewer irregular periods on myo-inositol (RR 0.78, 95% CI 0.68 to 0.89) and no significant effect on clinical pregnancy rate [10].
- Population
- Women with PCOS in assisted reproduction [8][10]. Women undergoing IVF, with and without PCOS [9].
- Sources
- [8], [9], [10]
- Caveats
- The reviews disagree on clinical pregnancy [8][10]. None of the abstracts reports live births for inositol. Heterogeneity was high for several outcomes [8][10].
PCOS
Limited evidence: all 4 PCOS trials were rated at high risk of compromised integrity, so their reported improvements were judged not reliable.
The numbers and sources
- Effect
- An integrity-based systematic review found 4 RCTs of berberine in polycystic ovary syndrome. All four were rated at high risk of compromised integrity, with absent trial registration, implausible recruitment timelines and possible duplicated data, so none was pooled. The reported improvements in insulin resistance, lipids and androgen markers were judged not reliable [7].
- Population
- 452 women with polycystic ovary syndrome, now also called polyendocrine metabolic ovarian syndrome [7].
- Sources
- [7]
- Caveats
- Trial authors did not answer requests for clarification [7]. The abstract does not name the four trials, so it does not show whether the PCOS trial in [6] was among them.
Excess hair and androgens in PCOS
Not shown to change hair growth scores or SHBG in women with PCOS in one review. Total testosterone fell slightly against placebo.
Compared with placebo [73]; placebo, metformin, short-acting contraceptives, ovulation drugs or assisted reproduction without vitamin D [69]
The numbers and sources
- Effect
- Across 13 RCTs (840 women), modified Ferriman-Gallwey hair scores (MD 0.04, 95% CI -0.79 to 0.86) and SHBG (MD 1.33, 95% CI -2.70 to 5.36) did not differ from placebo. Total testosterone fell by 0.17 (95% CI 0.05 to 0.29) and serum vitamin D rose by 17.81 [73]. A review of add-on vitamin D in women seeking pregnancy also found lower androgen levels (MD -2.31, 95% CI -3.51 to -1.11) [69].
- Population
- 840 women with PCOS in 13 RCTs [73]; 1,961 women with PCOS in 20 RCTs [69].
- Sources
- [73], [69]
- Caveats
- The abstract of [73] does not give units for testosterone or vitamin D. The hair score result rests on one review.
Therapies
Ovulation and pregnancy in PCOS
Not shown to raise live births, ovulation or pregnancy over sham acupuncture in women with PCOS. Side effects were slightly more common with true acupuncture.
Compared with sham acupuncture [34]; relaxation, clomiphene, physical exercise or no intervention, and the pill Diane-35 [34]
The numbers and sources
- Effect
- Against sham, live birth (RR 0.97, 95% CI 0.76 to 1.24, 1 RCT, 926 women), ovulation (SMD 0.02, 95% CI -0.15 to 0.19, 2 RCTs, 1,010 women), clinical pregnancy (RR 1.03, 95% CI 0.82 to 1.29, 3 RCTs, 1,117 women) and miscarriage did not clearly differ. Days between periods may have fallen (1 RCT, 141 women). Adverse events were more common with true acupuncture (RR 1.16, 95% CI 1.02 to 1.31, 3 RCTs, 1,230 women, moderate quality) [34].
- Population
- 1,546 women with PCOS and infrequent or absent ovulation in 8 RCTs [34].
- Sources
- [34]
- Caveats
- Evidence ranged from very low to moderate quality, and 7 of 8 trials had a high risk of bias in at least one domain. Other comparisons did not report live birth [34].
Practices
Cycles, androgens and blood sugar in PCOS
Shown in one small meta-analysis to lower menstrual irregularity, signs of excess androgens, fasting glucose and insulin resistance in women with PCOS, at low strength of evidence.
Compared with controls the source abstract does not describe [21]; conventional physical activity, routine care or no intervention [22]
The numbers and sources
- Effect
- Pooling 2 RCTs, yoga lowered menstrual irregularity (MD -0.41, 95% CI -0.74 to -0.08), clinical hyperandrogenism (MD -0.70, 95% CI -1.15 to -0.26), fasting glucose (MD -0.22 mmol/L, 95% CI -0.44 to -0.01), fasting insulin (MD -28.21 pmol/L, 95% CI -43.79 to -12.63) and HOMA-IR (MD -0.86, 95% CI -1.29 to -0.43) [21]. A 2026 review of trials with 258 participants found fasting glucose fell 4.50 mg/dL more than in controls in one trial (95% CI 2.39 to 6.61) and did not differ significantly in another. In one trial, testosterone did not change significantly and LH fell [22].
- Population
- 515 women with PCOS in 11 studies, 2 RCTs pooled [21]; 258 women with PCOS in RCTs [22].
- Sources
- [21], [22]
- Caveats
- The authors of [21] rated the strength of evidence low. [22] could not pool its trials, and three of its five reports came from one trial.
Daily life
Insulin resistance and weight in PCOS, in trials
Shown in trials to lower fasting insulin and insulin resistance slightly in women with PCOS. Fasting glucose did not change, at very low to low quality.
Compared with usual care or control groups [27]; before exercise, including trials with no control group [28]
The numbers and sources
- Effect
- Against control, exercise lowered fasting insulin (MD -2.44 µIU/mL, 95% CI -4.24 to -0.64) and HOMA-IR (MD -0.57, 95% CI -0.99 to -0.14), both very low quality, and LDL cholesterol and triglycerides. Waist fell 2.62 cm and BMI 1.02 kg/m2 after the programs. Fasting glucose and blood pressure did not change. Exercise added to diet did not differ from diet alone [27]. Vigorous exercise was linked to a 36.2% fall in HOMA-IR, a 4.2% fall in waist circumference and a 24.2% rise in VO2peak [28].
- Population
- 18 trials in women with PCOS [27]; 777 women in 19 studies, including uncontrolled trials, of 6 to 26 weeks [28].
- Sources
- [27], [28]
- Caveats
- Many effects were modest with wide intervals and shifted when single trials were added or removed [27]. [28] pooled controlled and uncontrolled studies.
Diets
Weight and insulin resistance in PCOS
Shown in pooled studies to lower weight and insulin resistance in women with PCOS. Against other diets, the reviews disagreed on weight.
Compared with other diets [21]; low-calorie diets [22]; before the diet, in the same women [21][22][23]
The numbers and sources
- Effect
- Against other diets, ketogenic diets lowered weight 4.98 kg more (95% CI 0.91 to 9.05), BMI 1.65 kg/m2 more and insulin resistance more (MD -1.71, 95% CI -2.98 to -0.43, I² 90%). From before to after the diet, weight fell 10.77 kg and BMI 3.38 kg/m2 [21]. In 2 RCTs against low-calorie diets, body weight did not differ significantly, while BMI, fat mass, glucose and HOMA-IR fell more on the ketogenic diets [22]. A third review of 7 studies found weight, BMI, glucose, insulin, HOMA-IR, LDL cholesterol and triglycerides fell from before to after the diet [23].
- Population
- Women with PCOS, most with BMI above 25, in 15 studies, 10 pooled [21]; 10 studies including 3 RCTs, 4 cohorts and 2 case series [22]; 7 studies [23].
- Sources
- [21], [22], [23]
- Caveats
- Heterogeneity was high for most outcomes [21]. Before-and-after results cannot separate the diet from weight loss or time. A published letter disputed whether the definition of real-world exposure in [21] matched its inclusion criteria [24].
Reproductive hormones and cycles in PCOS
Shown in pooled studies, mostly before and after the diet, to lower LH and testosterone and raise SHBG in women with PCOS. Against other diets, androgen results were inconsistent.
Compared with before the diet, in the same women [25][23][21][22]; other diets [21]; low-calorie diets [22]
The numbers and sources
- Effect
- After 45 days or more on a ketogenic diet, the LH to FSH ratio fell (d -0.851, 95% CI -1.015 to -0.686), free testosterone fell (d -0.223, 95% CI -0.328 to -0.119) and SHBG rose (d 9.086, 95% CI 3.379 to 14.792) [25]. A second review found lower LH, LH to FSH ratio, free and total testosterone and higher SHBG and FSH after the diet [23]. Menstrual cycle length shortened and LH fell from before to after the diet, while androgen results against other diets were inconsistent [21]. In 2 RCTs, LH was lower than on low-calorie diets [22].
- Population
- Women with PCOS in single- or double-arm clinical trials [25]; 7 studies [23]; 15 studies, 10 pooled [21]; 10 studies including 3 RCTs [22].
- Sources
- [25], [23], [21], [22]
- Caveats
- Diets lasted weeks to months, and all reviews were limited by small, mostly uncontrolled studies. Pregnancy and live birth data were too scarce to pool [23].
Weight and insulin resistance in PCOS
Shown in one meta-analysis of 8 trials to lower BMI and insulin resistance more than a regular diet in women with PCOS.
Compared with a regular diet with about 45% of energy from carbohydrate [13]; before the diet, in the same women [14]
The numbers and sources
- Effect
- Against a regular diet, low-carbohydrate diets lowered BMI (SMD -1.04, 95% CI -1.38 to -0.70), HOMA-IR (SMD -0.66, 95% CI -1.01 to -0.30), total cholesterol (SMD -0.68) and LDL cholesterol (SMD -0.66, 95% CI -1.30 to -0.02) [13]. A second review of 25 diet studies in PCOS found insulin resistance fell from before to after diets with under 50% of energy from carbohydrate (standardized paired difference -0.86, 95% CI -1.23 to -0.50) [14].
- Population
- 327 women with PCOS in 8 RCTs [13]; women with PCOS in 25 prospective diet studies [14].
- Sources
- [13], [14]
- Caveats
- Trials were small. The second review measured change within each diet group rather than against another diet [14].
Testosterone and SHBG in PCOS
In one meta-analysis, testosterone fell and SHBG rose more than on a regular diet only in trials of women with PCOS lasting longer than 4 weeks.
Compared with a regular diet with about 45% of energy from carbohydrate [13]
The numbers and sources
- Effect
- In trials of low-carbohydrate diets lasting more than 4 weeks, testosterone fell (SMD -1.79, 95% CI -3.22 to -0.36), SHBG rose (MD 5.98, 95% CI 3.51 to 8.46) and FSH rose (MD 0.39) more than on a regular diet. Diets low in both fat and carbohydrate raised SHBG and FSH more than higher-fat versions [13].
- Population
- 327 women with PCOS in 8 RCTs [13].
- Sources
- [13]
- Caveats
- These are subgroup results by trial length, from small trials. The abstract does not report an overall pooled effect on testosterone or SHBG [13].
On a blood test: High-sensitivity C-reactive protein (hs-CRP)
Every finding in the library that measured this test, including studies that were mainly about something else (leaving out those done only in men or only in children).
Shown to lower it
- StrongThunder god vineCautionRheumatoid arthritis
Across 40 RCTs (3,092 patients), tripterygium glycosides added to DMARDs lowered morning stiffness, tender and swollen joint counts, pain scores, CRP, ESR and rheumatoid factor against DMARDs alone (all p < .001).
- StrongTurmericC-reactive protein and other inflammation markers
Shown to lower CRP and some other inflammation markers in adults with inflammatory conditions or diabetes. These are blood markers, not clinical outcomes.
- StrongTurmericRheumatoid arthritis
Across 7 RCTs, DAS28 fell by 1.47 (95% CI -1.68 to -1.26), with lower rheumatoid factor, ESR and CRP.
- ModerateOral corticosteroidsSevere COVID-19 and pneumonia in hospital
In severe community-acquired pneumonia, added corticosteroids lowered deaths (RR 0.47, 95% CI 0.3 to 0.74) and C-reactive protein on day 8 (SMD -0.8, 95% CI -1.11 to -0.5), with no difference in gastrointestinal bleeding or high blood sugar.
- ModerateBeta-sitosterolBlood pressure and other heart risk markers
Plant sterols and stanols lowered systolic blood pressure by 1.55 mmHg (95% CI 0.42 to 2.67), diastolic by 0.84 mmHg, apoB by 0.06 g/L and hs-CRP by 0.25 mg/L.
- ModerateFisetin and quercetin (senolytics)Liver enzymes and lipids in fatty liver disease (quercetin alone)
A 2025 meta-analysis of 7 RCTs (540 patients) with metabolic dysfunction-associated steatotic liver disease found that quercetin lowered ALT, AST, GGT, direct bilirubin and C-reactive protein, lowered total cholesterol, LDL and triglycerides, and raised HDL.
- ModerateGarlicInflammation markers
Shown to lower CRP by about 0.6 mg/L and lower TNF in adults. These are blood markers, and the reviews disagree on IL-6.
- ModerateGingerInflammation markers
Shown to lower CRP, TNF-α and IL-6 in adults, more in people with health conditions. These are blood markers, not clinical outcomes.
- ModerateProbioticsRheumatoid arthritis
Mixed results: reviews agree probiotics lower CRP or IL-6 in rheumatoid arthritis, but disagree on disease activity.
- ModerateTart cherryRecovery after strenuous exercise
A 2026 meta-analysis of 19 trials in trained athletes found faster recovery of maximal strength at every time point (ES 0.63 right after exercise to 4.82 at 96 hours) and lower CRP up to 48 hours (ES -0.46 to -0.73).
- ModerateVitamin DInflammatory bowel disease
In adults, the Harvey Bradshaw Index for Crohn's disease fell by 1.47 points (95% CI -2.47 to -0.47) and hs-CRP fell by 1.58 mg/L.
- ModerateZincBlood sugar
Across 32 placebo-controlled interventions (1,700 participants, 14 countries), zinc lowered fasting glucose by 14.15 mg/dL (95% CI -17.36 to -10.93), 2-hour glucose by 36.85 mg/dL, HbA1c by 0.55% (95% CI -0.84 to -0.27) and hs-CRP by 1.31 mg/L.
- ModerateRed light therapyWeight and waist size in obesity
Across 11 RCTs (569 patients), photobiomodulation improved waistline (mean difference -7.28, 95% CI -9.97 to -5.67), weight (-3.54, 95% CI -5.97 to -1.11) and BMI (-1.18, 95% CI -1.93 to -0.43), and lowered C-reactive protein, total cholesterol and HOMA-IR.
- ModeratePaleo dietInflammation markers
Shown in two reviews to lower CRP about 0.4 to 0.8 mg/L more than comparison diets in adults, with one result sensitive to single trials.
Compared with control diets the source does not describe; a control group the source does not describe
- LimitedBoronJoint pain and arthritis
In 60 adults with knee osteoarthritis, 15 days of calcium fructoborate improved C-reactive protein, fibrinogen and sedimentation rate against placebo, with no serious adverse events.
- LimitedGrape seed extractInflammation
Limited evidence: a 50-trial review found lower CRP, while an earlier review found no effect.
- LimitedTart cherryKnee osteoarthritis pain
One trial found knee pain scores did not differ significantly from placebo in adults with knee osteoarthritis, though CRP fell.
- LimitedUrolithin AMitochondrial and cellular markers
Acylcarnitines, ceramides and CRP fell more than on placebo in older adults over 4 months, and acylcarnitines and CRP fell in middle-aged adults.
- LimitedLymphatic drainage massageMuscle recovery after hard exercise
One trial of 36 combat athletes found drainage after jumping exercise raised pain thresholds and lowered creatine kinase and C-reactive protein more than passive rest.
Compared with passive rest; intense sports massage
- LimitedJuice cleanseStudied in womenInflammation
One trial found the inflammation marker hs-CRP fell on a 7-day lemon detox but not on a calorie-matched placebo juice, in overweight Korean women.
Compared with before the diet, in the same people (overweight Korean women), with a calorie-matched placebo juice group measured the same way
Shown to raise it
- ModerateCLAInflammation and oxidative stress markers
Shown to raise CRP in adults across 14 studies. Sources disagree on oxidative stress, with one marker rising and another falling.
Studies disagree
- StrongDietary nitrateRecovery from muscle damage
Creatine kinase and oxidative stress did not change; C-reactive protein was higher than placebo at 48 hours (SMD 0.55). CRP, IL-6 and TNF-α did not change.
- StrongTart cherryBlood pressure and cardiometabolic markers
Across 21 trials, blood pressure, heart rate, hs-CRP and IL-6 did not change, while CRP fell by 0.39 mg/L (95% CI -0.74 to -0.05, moderate certainty).
- StrongVitamin DRheumatoid arthritis disease activity
Shown to lower disease activity modestly in adults with rheumatoid arthritis. Reviews disagree on CRP, ESR and pain.
- ModerateResveratrolInflammation and blood lipids
Mixed results: reviews disagree on whether CRP falls, and most found no change in LDL or triglycerides.
- ModerateFermented foodsInflammation and C-reactive protein
Mixed results: one meta-analysis found fermented dairy lowered C-reactive protein slightly, while two meta-analyses of kefir trials found no change.
Compared with control groups the abstract does not describe; people who did not drink kefir; control groups; a high-fiber diet, with changes measured over time in each group
- ModerateOlive oilInflammation
Mixed results: one pooled analysis found C-reactive protein fell 0.64 mg/L with olive oil, while a later one found no change in C-reactive protein or interleukin-6.
Compared with control groups, with control diets that varied; trials comparing olive oil or flaxseed oil with controls
- ModerateWhole grainsC-reactive protein and inflammation
Mixed results: two pooled analyses of trials found whole grains lowered C-reactive protein slightly, while a third found no significant change.
Compared with refined grains; refined grains or placebo; control diets low in or without whole grains
- ModerateKeto dietInflammation markers
Mixed results: CRP fell 0.62 mg/dL in one review of short and long trials, and a review of trials lasting a year or more found no CRP difference.
Compared with diets that did not restrict carbohydrates to the level of ketosis
- LimitedFish oilInflammation markers (CRP)
Limited evidence: CRP fell in hemodialysis patients but not with high-dose EPA, in knee osteoarthritis, or in most trials of trained people.
- LimitedPalmitoylethanolamideInflammation markers (CRP, IL-6)
Small trials found lower IL-6 and CRP in diabetic nerve pain, while a COVID-19 trial lowered other markers but not those two.
- LimitedMeditationInflammation and C-reactive protein
Mixed results: one meta-analysis found C-reactive protein fell against active controls, while a review of trials found a fall in three of six that measured it.
Compared with active control groups; waiting list, usual care and active control groups
Tested, and not shown to change it
- StrongTMGHigher cholesterol
Triglycerides, HDL, glucose, CRP, liver enzymes and blood pressure did not change.
- StrongVitamin DPsoriasis severity
Across 4 studies (333 patients), PASI, DLQI and CRP changes did not differ from control.
- StrongNutsInflammation and blood vessel function
Not shown to lower C-reactive protein in two meta-analyses of nut trials. Blood vessel widening, a measure of vessel function, improved in one.
Compared with control conditions the abstract does not describe; control arms without nuts
- ModerateAstaxanthinOxidative stress and inflammation
Shown to lower blood malondialdehyde, an oxidative stress marker, and IL-6 in type 2 diabetes. CRP and TNF-alpha did not change.
- ModerateFish oilCardiovascular outcomes with purified EPA (prescription)
Across 6 trials (42,738 adults) of 1.8 g a day or more of EPA-dominant omega-3, hospitalization for unstable angina fell (RR 0.75, 95% CI 0.66 to 0.87), while cardiovascular death, ischemic stroke and hs-CRP did not change significantly.
- ModerateFish oilRheumatoid arthritis
Across 18 RCTs (1,018 patients), tender joint count fell (SMD -0.59, 95% CI -0.79 to -0.39), while ESR, CRP and DAS28 did not change significantly.
- ModerateLactoferrinRespiratory infections
In adults, IL-6 fell by 24.9 pg/mL, while CRP and NK cell activity did not change.
- ModerateRhodiolaEndurance performance
Creatine kinase (ES -0.84) and lactate fell, and IL-6 and CRP did not change.
- ModerateCold water immersionInflammation
Not shown to lower inflammation. Inflammatory markers rose in the hour after immersion, and post-exercise reviews found no change in C-reactive protein or interleukin-6.
- ModerateWhole-body cryotherapyAnkylosing spondylitis
Shown to improve pain, function and disease activity scores in people with ankylosing spondylitis in a meta-analysis of 5 studies. C-reactive protein did not change.
- ModerateHigh-protein dietBlood pressure and triglycerides
Total and LDL cholesterol, C-reactive protein and HbA1c did not change.
Compared with diets with less protein
- ModerateNordic dietInflammation markers
Not shown to change CRP, IL-6 or TNF-alpha in adults in Nordic countries.
Compared with control groups the source does not describe
- LimitedDeer antler velvetArthritis
In 168 people with rheumatoid arthritis on standard treatment, 6 months of elk velvet antler did not differ from placebo on joint pain and swelling, disease activity, function, quality of life or CRP.
- LimitedGreen-lipped musselInflammation markers (CRP)
Small trials found no change in CRP in knee osteoarthritis, and lower airway inflammation markers in asthma.
- LimitedL-carnitineTMAO and cardiovascular markers
In healthy older women, 24 weeks of L-carnitine raised plasma TMAO tenfold but did not change CRP, IL-6, adhesion molecules or lipids.
- LimitedCuppingInflammation, wet cupping
One trial of 126 people with metabolic syndrome found wet cupping did not change high-sensitivity C-reactive protein over 12 weeks.
Compared with dietary advice alone
On a blood test: Fasting insulin and HOMA-IR
Every finding in the library that measured this test, including studies that were mainly about something else (leaving out those done only in men or only in children).
Shown to lower it
- StrongKeto dietStudied in womenWeight and insulin resistance in PCOS
Shown in pooled studies to lower weight and insulin resistance in women with PCOS. Against other diets, the reviews disagreed on weight.
Compared with other diets; low-calorie diets; before the diet, in the same women
- ModerateAlpha-lipoic acidBlood sugar
Across 63 trials, fasting glucose fell 5.28 mg/dL (95% CI -7.21 to -3.35), HbA1c 0.40% (95% CI -0.66 to -0.14), fasting insulin 1.70 mU/mL and HOMA-IR 0.74 against control.
- ModerateChromiumStudied in womenInsulin resistance
Shown to lower HOMA-IR and fasting insulin slightly in overweight adults and women with PCOS. Fasting glucose and HbA1c did not change significantly.
- ModerateVitamin DStudied in womenBlood sugar and insulin in PCOS
Shown in one review to lower fasting glucose and insulin slightly against placebo in women with PCOS. An earlier review found changes mainly with other nutrients.
Compared with placebo
- ModerateZincBlood sugar
Across 18 RCTs (1,023 participants) with diabetes, gestational diabetes or prediabetes, zinc lowered serum insulin (MD -2.50, 95% CI -4.69 to -0.31) and HOMA-IR (MD -1.10, 95% CI -2.05 to -0.15), and LDL cholesterol rose slightly (MD 3.46, 95% CI 1.48 to 5.43).
- ModerateYogaStudied in womenCycles, androgens and blood sugar in PCOS
Shown in one small meta-analysis to lower menstrual irregularity, signs of excess androgens, fasting glucose and insulin resistance in women with PCOS, at low strength of evidence.
Compared with controls the source abstract does not describe; conventional physical activity, routine care or no intervention
- ModeratePhysical activityStudied in womenInsulin resistance and weight in PCOS, in trials
Shown in trials to lower fasting insulin and insulin resistance slightly in women with PCOS. Fasting glucose did not change, at very low to low quality.
Compared with usual care or control groups; before exercise, including trials with no control group
- ModerateDark chocolateBlood vessel function and insulin resistance
Shown to improve blood vessel widening and lower insulin resistance in short trials of chocolate or cocoa, in one meta-analysis rated low to moderate quality.
Compared with control conditions the abstract does not describe
- ModerateNordic dietBlood sugar and insulin
Mixed results: fasting glucose did not change in adults, while fasting insulin and insulin resistance fell slightly.
Compared with an average Nordic diet with the same calories; control diets the source does not describe
- ModeratePaleo dietBlood sugar and insulin
Mixed results: two reviews found lower fasting insulin, while a review against Mediterranean, diabetes and guideline diets found no difference in glucose, insulin or HbA1c.
Compared with control diets the source does not describe; a control group the source does not describe; the Mediterranean diet, a diabetes diet and a diet following Dutch Health Council advice
- LimitedFiber supplementsBlood sugar
Across 12 RCTs in overweight and obese adults, isolated soluble fiber lowered fasting glucose by 0.17 mmol/L (95% CI -0.28 to -0.06) and fasting insulin by 15.88 pmol/L.
Tested, and not shown to change it
- StrongApple cider vinegarBlood sugar
Across 9 studies in adults, ACV lowered fasting glucose by 7.97 mg/dL (95% CI -13.74 to -2.21) and HbA1c by 0.50 (95% CI -0.90 to -0.09), with no change in fasting insulin or HOMA-IR.
- StrongTurmericBlood sugar
With piperine added, 15 RCTs (1,020 participants) showed fasting glucose 5.89 mg/dL lower, while HbA1c, fasting insulin and HOMA-IR did not differ significantly.
- StrongVegetarian dietBlood sugar in type 2 diabetes
In 9 RCTs (664 participants), HbA1c fell 0.29 points (95% CI -0.45 to -0.12) and fasting glucose 0.56 mmol/L, at moderate certainty, with no change in fasting insulin.
Compared with comparator diets the source does not describe; control diets the source does not describe
- ModerateMK-677Grey marketRaised blood sugar and lower insulin sensitivity
Shown to raise fasting blood sugar about 5 mg/dL and lower insulin sensitivity in older adults, with poorer glucose handling in obese men.
- Moderate
- ModerateGreen tea extractBlood sugar
Shown to lower fasting glucose, HbA1c and insulin resistance modestly with EGCG supplements in adults, with HbA1c down about 0.18 points.
- ModerateMilk thistleBlood sugar in type 2 diabetes
Across 6 RCTs (673 participants), HOMA-IR fell by 2.29 (95% CI -4.55 to -0.03) with no change in fasting insulin.
- ModerateRed light therapyWeight and waist size in obesity
Fat mass percentage (-0.28, 95% CI -1.25 to 0.69), waist-to-hip ratio and insulin did not differ.
- ModerateNutsBlood sugar in type 2 diabetes
Fasting insulin and HOMA-IR did not change significantly.
Compared with diets with the same calories without tree nuts
- ModerateWhole grainsBlood sugar in trials
In 16 trials lasting weeks to months, fasting glucose, fasting insulin and HOMA-IR did not change significantly.
Compared with similar refined foods; refined grains or placebo
- LimitedSermorelinBlood sugar and laboratory changes
Small studies found no change in fasting glucose, insulin or lipids in children over 1 year and in older men over 6 weeks.
- Limited
On a blood test: HOMA-IR
Every finding in the library that measured this test, including studies that were mainly about something else (leaving out those done only in men or only in children).
Shown to lower it
- StrongOrlistatLiver enzymes in fatty liver disease
LDL cholesterol fell 5.61 mg/dL, fasting glucose 4.05 mg/dL, HOMA-IR 0.70 and BMI 0.99 kg/m².
- StrongBerberineBlood sugar in type 2 diabetes
Against placebo in 20 trials (1,761 participants), it lowered fasting glucose by 0.52 mmol/L (95% CI -0.72 to -0.33) and HOMA-IR by 0.85.
- StrongTurmericBlood sugar
Across 34 RCTs in adults with prediabetes or type 2 diabetes, curcumin or turmeric lowered fasting glucose by 10.15 mg/dL (95% CI -12.59 to -7.72), HbA1c by 0.32% (95% CI -0.43 to -0.21) and HOMA-IR by 0.46 against control.
- StrongKeto dietStudied in womenWeight and insulin resistance in PCOS
In 2 RCTs against low-calorie diets, body weight did not differ significantly, while BMI, fat mass, glucose and HOMA-IR fell more on the ketogenic diets.
Compared with other diets; low-calorie diets; before the diet, in the same women
- ModerateAlpha-lipoic acidBlood sugar
Across 63 trials, fasting glucose fell 5.28 mg/dL (95% CI -7.21 to -3.35), HbA1c 0.40% (95% CI -0.66 to -0.14), fasting insulin 1.70 mU/mL and HOMA-IR 0.74 against control.
- ModerateChromiumStudied in womenInsulin resistance
Shown to lower HOMA-IR and fasting insulin slightly in overweight adults and women with PCOS. Fasting glucose and HbA1c did not change significantly.
- ModerateInositolWeight, blood sugar and lipids
In 18 RCTs (898 participants) of at least 4 weeks, inositol lowered BMI by 0.57 kg/m² (95% CI -1.10 to -0.03), waist circumference by 2.36 cm, glucose by 7.25 mg/dL, HOMA-IR by 1.21, triglycerides by 29.80 mg/dL, LDL cholesterol by 5.15 mg/dL, and systolic and diastolic pressure by 5.34 and 6.12 mm Hg.
- ModerateMagnesiumBlood sugar and insulin resistance
One meta-analysis found magnesium lowered HOMA-IR (WMD -0.67, 95% CI -1.20 to -0.14) but not fasting glucose (WMD -0.20 mmol/L, 95% CI -0.45 to 0.05) or HbA1c overall.
- ModerateMilk thistleBlood sugar in type 2 diabetes
A 2025 network meta-analysis of 17 studies (1,337 people with type 2 diabetes) found silymarin lowered fasting glucose, HOMA-IR and HbA1c against placebo (P < 0.05).
- ModerateZincBlood sugar
Across 18 RCTs (1,023 participants) with diabetes, gestational diabetes or prediabetes, zinc lowered serum insulin (MD -2.50, 95% CI -4.69 to -0.31) and HOMA-IR (MD -1.10, 95% CI -2.05 to -0.15), and LDL cholesterol rose slightly (MD 3.46, 95% CI 1.48 to 5.43).
- ModerateRed light therapyWeight and waist size in obesity
Across 11 RCTs (569 patients), photobiomodulation improved waistline (mean difference -7.28, 95% CI -9.97 to -5.67), weight (-3.54, 95% CI -5.97 to -1.11) and BMI (-1.18, 95% CI -1.93 to -0.43), and lowered C-reactive protein, total cholesterol and HOMA-IR.
- ModerateYogaStudied in womenCycles, androgens and blood sugar in PCOS
Pooling 2 RCTs, yoga lowered menstrual irregularity (MD -0.41, 95% CI -0.74 to -0.08), clinical hyperandrogenism (MD -0.70, 95% CI -1.15 to -0.26), fasting glucose (MD -0.22 mmol/L, 95% CI -0.44 to -0.01), fasting insulin (MD -28.21 pmol/L, 95% CI -43.79 to -12.63) and HOMA-IR (MD -0.86, 95% CI -1.29 to -0.43).
Compared with controls the source abstract does not describe; conventional physical activity, routine care or no intervention
- ModeratePhysical activityStudied in womenInsulin resistance and weight in PCOS, in trials
Against control, exercise lowered fasting insulin (MD -2.44 µIU/mL, 95% CI -4.24 to -0.64) and HOMA-IR (MD -0.57, 95% CI -0.99 to -0.14), both very low quality, and LDL cholesterol and triglycerides.
Compared with usual care or control groups; before exercise, including trials with no control group
- ModerateDark chocolateBlood vessel function and insulin resistance
HOMA-IR fell 0.67 (95% CI 0.36 to 0.98) through lower serum insulin.
Compared with control conditions the abstract does not describe
- ModerateFermented foodsBlood sugar
Kefir lowered fasting glucose (MD -8.46 mg/dL) and HOMA-IR (MD -1.71).
Compared with control groups the abstract does not describe; conventional yogurt
- ModerateIntermittent fastingBlood sugar
In adults without diabetes, time-restricted eating without calorie restriction lowered fasting glucose by 2.65 mg/dL (95% CI -3.92 to -1.39) and HOMA-IR by 0.58.
Compared with a control diet with no time restriction; unrestricted eating; daily calorie restriction or a control group; standard-of-care nutritional counseling alone
- ModerateLow-carb dietStudied in womenWeight and insulin resistance in PCOS
Against a regular diet, low-carbohydrate diets lowered BMI (SMD -1.04, 95% CI -1.38 to -0.70), HOMA-IR (SMD -0.66, 95% CI -1.01 to -0.30), total cholesterol (SMD -0.68) and LDL cholesterol (SMD -0.66, 95% CI -1.30 to -0.02).
Compared with a regular diet with about 45% of energy from carbohydrate; before the diet, in the same women
- ModerateNordic dietBlood sugar and insulin
In 6 RCTs (618 participants, 6 to 26 weeks), fasting glucose did not change (-0.05 mmol/L, 95% CI -0.13 to 0.01), while fasting insulin fell 1.12 mU/L and HOMA-IR 0.34 against control diets.
Compared with an average Nordic diet with the same calories; control diets the source does not describe
Shown to raise it
- ModerateSleep durationLower insulin sensitivity with short sleep
Shown to lower insulin sensitivity when sleep was restricted, in a meta-analysis of randomized trials, measured by glucose tolerance tests, HOMA-IR and the clamp.
- LimitedLight at nightRoom light during sleep raised next-morning insulin resistance
After one night with overhead room light at 100 lux, HOMA-IR rose about 15%, against a 4% fall after a second dim night (p = 0.018).
Studies disagree
- StrongMetforminStudied in womenInsulin resistance and blood sugar in PCOS
Against placebo, metformin lowered HOMA-IR by 0.50 (95% CI 0.09 to 0.91) and fasting glucose by 0.13 mmol/L (95% CI 0.07 to 0.19), both moderate certainty.
Compared with placebo; lifestyle change with or without placebo; combined oral contraceptive pills
Tested, and not shown to change it
- StrongApple cider vinegarBlood sugar
In 7 controlled trials in type 2 diabetes, ACV lowered fasting blood sugar by 21.9 mg/dL (95% CI -29.19 to -14.67) and HbA1c by 1.53 (95% CI -2.65 to -0.41), with no change in HOMA-IR.
- StrongFenugreekBlood sugar in diabetes
A 2023 meta-analysis of 10 RCTs (706 participants) with type 2 diabetes or prediabetes also reported lower fasting glucose, 2-hour glucose and HbA1c, and no change in HOMA-IR.
- Moderate
- Moderate
- Moderate
- ModerateNMNInsulin sensitivity and metabolic markers
In the 60-day dose trial, HOMA-IR did not differ from placebo.
- ModerateResveratrolBlood sugar and insulin sensitivity
A 2026 umbrella review pooling 10 meta-analyses in type 2 diabetes found no significant effect on fasting glucose, HbA1c, insulin or HOMA insulin resistance.
- ModerateNutsBlood sugar in type 2 diabetes
Fasting insulin and HOMA-IR did not change significantly.
Compared with diets with the same calories without tree nuts
- ModerateAlternate-day fastingBlood sugar in people without diabetes
Fasting glucose (p 0.09) and HOMA-IR (p 0.55) did not differ from control.
Compared with eating every day, with no fasting days or daily fasting window
- Limited
On a blood test: Total testosterone
Every finding in the library that measured this test, including studies that were mainly about something else (leaving out those done only in men or only in children).
Shown to lower it
- ModerateHormonal birth controlStudied in womenLower testosterone and higher SHBG
Shown to lower total testosterone and cut free testosterone by about 61% in healthy women on combined pills, while SHBG rose about 99 nmol/L.
- ModerateSARMsGrey marketLower testosterone and HDL cholesterol
Shown to lower testosterone and HDL cholesterol in healthy men, more at higher doses. Levels returned to baseline after stopping.
- ModerateInositolStudied in womenHormones and blood sugar in PCOS
Shown to lower free and total testosterone and glucose and raise SHBG in women with PCOS. Metformin did better on hirsutism.
- ModerateVitamin DStudied in womenExcess hair and androgens in PCOS
Not shown to change hair growth scores or SHBG in women with PCOS in one review. Total testosterone fell slightly against placebo.
Compared with placebo; placebo, metformin, short-acting contraceptives, ovulation drugs or assisted reproduction without vitamin D
- ModerateKeto dietStudied in womenReproductive hormones and cycles in PCOS
Shown in pooled studies, mostly before and after the diet, to lower LH and testosterone and raise SHBG in women with PCOS. Against other diets, androgen results were inconsistent.
Compared with before the diet, in the same women; other diets; low-calorie diets
- ModerateLow-carb dietStudied in womenTestosterone and SHBG in PCOS
In one meta-analysis, testosterone fell and SHBG rose more than on a regular diet only in trials of women with PCOS lasting longer than 4 weeks.
Compared with a regular diet with about 45% of energy from carbohydrate
- LimitedSpironolactoneStudied in womenHirsutism and cycles in PCOS
Testosterone fell in both groups, and weight and blood pressure did not change.
Compared with metformin 1,000 mg a day; metformin 1,700 mg a day alone; spironolactone alone
Shown to raise it
- StrongAshwagandhaTestosterone
Shown to raise testosterone in men, by about 57 ng/dL in one review, with no change in women. Rises stayed within physiological ranges.
- ModerateDHEAStudied in womenTestosterone and estradiol levels in postmenopausal women
Shown to raise testosterone by about 24 ng/dL and estradiol by about 8 pg/mL in postmenopausal women.
Studies disagree
- ModerateMetforminStudied in womenExcess hair and androgens in PCOS
Mixed results: against the pill, hair growth improved about the same in one review and less in overweight women in another. Metformin lowered testosterone against placebo.
Compared with combined oral contraceptive pills; metformin combined with the pill; placebo; lifestyle change with or without placebo
Tested, and not shown to change it
- LimitedMinoxidilLow-dose sublingual against placebo
Testosterone levels did not change and no serious adverse events occurred.
On a blood test: Free testosterone
Every finding in the library that measured this test, including studies that were mainly about something else (leaving out those done only in men or only in children).
Shown to lower it
- ModerateHormonal birth controlStudied in womenLower testosterone and higher SHBG
Shown to lower total testosterone and cut free testosterone by about 61% in healthy women on combined pills, while SHBG rose about 99 nmol/L.
- ModerateSARMsGrey marketLower testosterone and HDL cholesterol
FSH and free testosterone fell at the highest dose.
- ModerateInositolStudied in womenHormones and blood sugar in PCOS
Against placebo, inositol lowered BMI (MD -0.45), free testosterone (MD -0.41), total testosterone (MD -20.4) and glucose (MD -3.14), and raised sex-hormone-binding globulin (MD 32.1).
- ModerateKeto dietStudied in womenReproductive hormones and cycles in PCOS
After 45 days or more on a ketogenic diet, the LH to FSH ratio fell (d -0.851, 95% CI -1.015 to -0.686), free testosterone fell (d -0.223, 95% CI -0.328 to -0.119) and SHBG rose (d 9.086, 95% CI 3.379 to 14.792).
Compared with before the diet, in the same women; other diets; low-calorie diets
On a blood test: Sex hormone binding globulin (SHBG)
Every finding in the library that measured this test, including studies that were mainly about something else (leaving out those done only in men or only in children).
Shown to lower it
- ModerateSARMsGrey marketLower testosterone and HDL cholesterol
LGD-4033 lowered total testosterone, sex hormone-binding globulin, HDL cholesterol and triglycerides in a dose-dependent way.
Shown to raise it
- ModerateHormonal birth controlStudied in womenLower testosterone and higher SHBG
Shown to lower total testosterone and cut free testosterone by about 61% in healthy women on combined pills, while SHBG rose about 99 nmol/L.
- ModerateInositolStudied in womenHormones and blood sugar in PCOS
Shown to lower free and total testosterone and glucose and raise SHBG in women with PCOS. Metformin did better on hirsutism.
- ModerateKeto dietStudied in womenReproductive hormones and cycles in PCOS
Shown in pooled studies, mostly before and after the diet, to lower LH and testosterone and raise SHBG in women with PCOS. Against other diets, androgen results were inconsistent.
Compared with before the diet, in the same women; other diets; low-calorie diets
- ModerateLow-carb dietStudied in womenTestosterone and SHBG in PCOS
In one meta-analysis, testosterone fell and SHBG rose more than on a regular diet only in trials of women with PCOS lasting longer than 4 weeks.
Compared with a regular diet with about 45% of energy from carbohydrate
Tested, and not shown to change it
- Moderate
- ModerateVitamin DStudied in womenExcess hair and androgens in PCOS
Not shown to change hair growth scores or SHBG in women with PCOS in one review. Total testosterone fell slightly against placebo.
Compared with placebo; placebo, metformin, short-acting contraceptives, ovulation drugs or assisted reproduction without vitamin D