Reproductive organs and sex hormones

Shown to lower gestational diabetes about 44% to 47% with myo-inositol in pregnant women. One trial in women with PCOS found no change in a combined outcome.

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]

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]

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]

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]

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]

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]

Shown to relieve period pain more than placebo, with moderate or excellent relief in 45% to 53% of women against 18% on placebo.

Compared with placebo [24][25]; paracetamol [24]; other NSAIDs and aspirin [24][25]

Shown to raise intercourse success to about 69% against 35% on placebo in men with erectile dysfunction, with no difference between sildenafil, vardenafil and tadalafil.

Shown in two reviews of trials to lower period pain in women with primary dysmenorrhea, by about 2 to 2.5 cm on a 10 cm pain scale.

Compared with no treatment [23]; mefenamic acid in one trial [23]; comparators of any kind, not described in the source abstract [24]

Shown to ease pain in women with endometriosis against placebo, by 2.58 points on a visual analogue pain scale for oral progestins in pooled trials.

Compared with placebo or no treatment, pooled together [5]; placebo [6][7][8]

Shown to raise satisfying sexual events, desire, arousal and orgasm, and lower sexual distress, in postmenopausal women. Long-term data are limited.

Shown to cut menstrual blood loss by about 47 to 53 mL a cycle more than placebo in women with heavy periods, about a 40% drop on the approved dose.

Compared with placebo [1][2][3][4][5]

Shown to control fibroid bleeding in about 91% of women against 19% on placebo, with amenorrhea in 47% to 82% against 2% to 6%, over 12 to 13 weeks.

Compared with placebo [1][2][3][4]

Shown in three reviews to lower period pain more than placebo in women with primary dysmenorrhea, by about 1.1 to 1.6 points on a 10-point scale.

Compared with placebo or standard care [63]; placebo, in trials that had a placebo group [64]; placebo [65]

Shown in two reviews to ease PMS symptoms more than placebo, with small to moderate drops in total, emotional and physical symptom scores.

Compared with placebo [20][21]; placebo across the zinc trials reviewed [22]

Shown in low-quality trials to ease period pain more than no treatment or NSAIDs, comparisons in which no one could be blinded.

Compared with no treatment [28][29]; NSAIDs [28][29]

Shown to cut preeclampsia by about 18% with low-dose aspirin in pregnancy, about 1 fewer case per 61 women treated.

Shown to raise sexual desire scores by about 0.35 points over placebo on a 1.2 to 6 scale in premenopausal women with low desire.

Shown to lower distress about low desire by about 0.33 points over placebo on a 0 to 4 scale in premenopausal women.

Shown to improve sexual function scores in people with antidepressant-related sexual problems at 150 mg twice daily in three trials, and not at 150 mg once daily.

Shown in several trials to ease PMS symptoms more than placebo. In the largest, total symptom scores fell 48% on calcium and 30% on placebo.

Compared with placebo [21][22]; placebo or usual diet across the trials reviewed [23]

Shown to reduce hot flashes in menopausal women by about one a day against placebo, an effect smaller than estrogen.

Compared with placebo [10]

Shown in several trials to ease PMS and PMDD symptoms more than a waiting list or no treatment. A 2009 review had found little evidence.

Compared with waiting list [20][22][23]; no intervention [21]

Shown to improve sexual function slightly in menopausal women overall, though oral DHEA alone did not differ from placebo.

Shown to lower pain during sex and vaginal dryness in postmenopausal women using intravaginal DHEA. This applies to the vaginal form, not oral DHEA.

Shown to raise testosterone by about 24 ng/dL and estradiol by about 8 pg/mL in postmenopausal women.

Shown to raise clinical pregnancy rates and eggs retrieved in women having IVF or ICSI, on low-quality evidence. Live birth data were insufficient.

Shown to shift urinary estrogen metabolite ratios in women on tamoxifen, breast cancer survivors and men with prostate cancer. No trial measured cancer outcomes.

Shown to ease endometriosis pain in women more than a sham diagnostic laparoscopy in two small blinded trials, with 80% against 32% improved after excision.

Compared with diagnostic laparoscopy alone, with the women unaware of their group (sham surgery) [1][2][3][4]

Shown to lower pain and cyst recurrence in women with endometriomas against drainage and ablation. Endometriomas recurred in 5% to 17% after excision against 37% after ablation.

Compared with drainage and ablation of the cyst [10]

Shown to lower endometriosis recurrence in women after conservative surgery when hormonal suppression followed, by about 59% against no treatment or placebo.

Compared with expectant management or placebo after surgery [13]

Shown to raise pregnancy rates slightly with 4 to 5 mg a day before conception against 0.4 mg. Fewer miscarriages appeared only among women who conceived.

Linked to about 30% lower autism risk and lower ADHD odds in children whose mothers took folic acid, in observational studies.

Shown to reduce the frequency and duration of menopausal hot flashes more than placebo on gabapentin, across seven trials.

Shown to lower period pain scores in women with primary dysmenorrhea when taken in the first 3 to 4 days of the cycle.

Shown to raise erectile function scores about 3.5 points on a 30-point scale in men with mild to moderate dysfunction, below the minimal important difference.

Shown to bring blood loss under 80 mL with at least a 50% drop in about 72% of women with fibroids, against 15% to 19% on placebo, over 24 weeks.

Compared with placebo [1][2]; controls the source abstract does not describe [3]

Shown to shrink the uterus by about 175 mL before surgery against placebo or no treatment, with fewer transfusions and complications at hysterectomy. Fibroids regrew after stopping.

Compared with placebo or no pretreatment [11]; other medicines before surgery, including ulipristal [11]

Shown to produce sperm in about 75% of men with hypogonadotropic hypogonadism, mostly with hCG combined with FSH.

Shown to ease period pain in women more than an unheated placebo patch, in two trials. Mean pain relief over 2 days was 3.27 with heat against 1.95 without.

Compared with an unheated patch with a placebo pill (sham) [4][5]

Shown to reduce period pain in women more than placebo, with improvement in 37% to 60% against 28%, along with more irregular bleeding, headache and nausea.

Compared with placebo or no treatment [5]

Shown to lower heavy menstrual blood loss more than other medicines, about 67 mL more, with fewer treatment failures, on the levonorgestrel IUD in women with heavy periods.

Compared with oral progestins, combined pills, mefenamic acid, tranexamic acid or usual medical treatment [6]; medroxyprogesterone acetate [3]

Shown to return heavy periods to normal in 12% to 77% of women on the combined pill, against 3% on placebo. The hormonal IUD lowered blood loss more.

Compared with placebo, NSAIDs, the levonorgestrel IUD, the vaginal ring and long-course progestogens [25]

Linked to lower ovarian cancer risk in women, 15% to 29% lower for every 5 years of pill use, with protection lasting over 30 years after stopping.

Compared with women who never used the pill [8]

Linked to lower endometrial cancer risk in women, about 24% lower for every 5 years of pill use, lasting over 30 years after stopping.

Compared with women who never used the pill [9]

Shown that 83% of women became pregnant within 12 months of stopping contraception, with no difference between hormonal methods and IUDs or by length of pill use.

Compared with other contraceptive methods, including IUDs [10]

Shown to ease endometriosis period pain more than placebo in two small trials, in very low-quality evidence. Pain at 6 months matched goserelin in one trial.

Compared with placebo [32][33]; goserelin [32]; oral progestins and GnRH agonists [33]

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.

Shown to lower free and total testosterone and glucose and raise SHBG in women with PCOS. Metformin did better on hirsutism.

Shown to halve anemia risk in non-anemic pregnant women, with no change in birth weight or preterm birth.

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]

Shown to raise the odds of improvement about 3 times over placebo in men with mild to moderate erectile dysfunction, at 1,500 to 5,000 mg a day.

Shown to raise total testosterone in men with low testosterone, by about 274 ng/dL against placebo, in pooled trials of clomiphene or enclomiphene.

Compared with placebo [13]; testosterone gel [13]; human chorionic gonadotropin [13]; the same men before treatment [14]

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]

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]

Shown to cut hot flash frequency about 75% relative to placebo in menopausal women, though placebo alone cut them about 58%.

Shown to lower menopause symptom scores and improve menopause quality of life against controls, with larger effects from estradiol-containing therapy.

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]

Shown to raise progesterone and endometrial thickness in women with PCOS. These are hormone and ultrasound measures, not pregnancy rates.

Shown to improve sperm concentration, motility, morphology and semen volume in men with infertility, measured as semen quality rather than pregnancy.

Shown to lower menstrual blood loss more than placebo in women with heavy periods. Tranexamic acid, danazol and the hormonal IUD lowered it more.

Compared with placebo, tranexamic acid, danazol, the levonorgestrel IUD, oral luteal progestogen, ethamsylate, the combined pill, an older progesterone IUD and other NSAIDs [23]

Shown in one review of trials to lower overall PMS symptoms more than no exercise, along with psychological, physical and behavioral symptoms, in trials mostly at high risk of bias.

Compared with non-exercise comparator groups [25]

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]

Shown to ease endometriosis pain in women about as much as GnRH agonist injections such as leuprolide, with less bone loss and fewer hot flushes.

Compared with GnRH agonists [5]; leuprolide injections [9][10][11][1]; a GnRH antagonist [5]

Shown to lower labor pain by about 1.9 points on a 0 to 10 scale and reduce anxiety, against placebo, usual care or no intervention.

Compared with placebo, usual care or no intervention [13]

Shown to reduce moderate and severe hot flashes in postmenopausal women on desvenlafaxine 100 mg, an unapproved use. Venlafaxine lowered hot flash scores in women with breast cancer.

Linked to 41% lower odds of breast cancer with higher soy isoflavone intake in studies of Asian women, with no clear link in Western women.

Compared with the lowest isoflavone intake [9]; 10 mg a day less isoflavones, in a dose-response model [10]; the lowest quartile, 4.5 mg a day [10]

Linked to 25% lower breast cancer recurrence at 10 mg or more of soy isoflavones a day after diagnosis, in pooled cohorts of US and Chinese women.

Compared with women eating under 10 mg of isoflavones a day [11]; the lowest soy and isoflavone intake [12]

Shown to reduce premenstrual symptoms in women with PMS or PMDD by a moderate amount, more with daily dosing than with dosing in the luteal phase only.

Shown to improve self-rated premature ejaculation in men, about 202 more per 1,000 than placebo, in a use no label cited here lists.

Shown to reduce hot flash frequency and severity modestly in menopausal women. Paroxetine 7.5 mg is the one SSRI product approved for this use.

Shown to lower PMS anxiety, depression, mood and behavioral symptoms modestly against placebo. One small trial found physical and behavioral gains but no mood change.

Shown to ease period pain in women by 1.39 points with high-frequency and 2.04 with low-frequency TENS, against sham or no treatment pooled together, at low certainty.

Compared with placebo TENS or no treatment, pooled together [5]

Shown to raise sexual desire, erectile function and satisfaction slightly in men with low testosterone, with effects small by usual standards.

Shown to raise total testosterone in men, including men with low testosterone, in few small trials, one run partly by the maker.

Shown to ease limits on social, leisure and physical activities during periods in women with heavy bleeding, compared with placebo.

Compared with placebo [2][4][5]

Shown to improve some sperm measures in infertile men in 6 of 7 studies, though results were not pooled and some studies had no control group.

Shown to raise the share of women free of menstrual migraine when frovatriptan was taken around the period, with about 4 to 7 treated for one extra.

Shown to control fibroid bleeding in 90% to 98% of women, as often as leuprolide injections at 89%, with moderate to severe hot flashes in 10% to 11% against 40%.

Compared with leuprolide injections [3][5][6]

Shown to shrink fibroids against placebo, a median 21% and 12% on 5 mg and 10 mg against a 3% rise, though less than GnRH agonists shrank the uterus.

Compared with placebo [1][3][6]; GnRH agonists [6]

Shown to improve fibroid symptom severity by about 20 points and quality of life by about 23 points on a 100-point scale, against placebo.

Compared with placebo [2][3]

Shown to lower pregnancies after unprotected sex compared with levonorgestrel emergency pills, 1.8% against 2.6% within 72 hours in the largest trial.

Compared with levonorgestrel emergency contraception [7][8]

Shown to cut heavy menstrual bleeding more than a hormonal IUD or endometrial ablation, ranking first in a network meta-analysis, with low-certainty evidence.

Compared with a levonorgestrel IUD and endometrial ablation [3]; uterine artery embolization [4]

Shown to need fewer blood transfusions than hysterectomy or myomectomy, with shorter hospital stays and a faster return to usual activities in every trial that measured them.

Compared with hysterectomy or myomectomy [5]

Shown to reduce heavy bleeding about as much as myomectomy at 4 years, in one randomized trial and one pooled analysis.

Compared with myomectomy [8][7]

Shown to cause less pain at 6 and 48 hours, about half the risk of fever and shorter hospital stays than open myomectomy, with no difference in fibroid recurrence.

Compared with open myomectomy, including mini-laparotomy [9]

Shown in pooled studies, mostly without a comparison group, to shrink treated fibroids about 65% by 12 months and to improve bleeding and quality of life scores.

Compared with before treatment, in the same women [14][15]

Shown to lower period pain against placebo or NSAIDs in women with primary dysmenorrhea, in few trials with high heterogeneity.

Shown to improve overall premenstrual symptoms and premenstrual depression over placebo in women with PMS, in mostly low-quality trials from a 1999 review.

Shown to shrink fibroids slightly or slow their growth against placebo over 2 to 3 months in women with fibroids, most with low vitamin D, in small trials.

Compared with placebo [56][58][59]; controls the source abstract does not describe [57]

Linked to fewer fibroids with higher vitamin D levels. Women with fibroids had about 6 ng/mL less vitamin D than women without, in pooled observational studies.

Compared with women without fibroids [57][60][61]; women with 25-hydroxyvitamin D below 20 or 30 ng/mL [62]

Shown in one review of 5 trials to lower overall PMS severity, physical symptoms and depression, at very low certainty. Anxiety, cravings and water retention did not change.

Compared with placebo or standard care [68]

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]

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]

Shown in pooled trials to ease pelvic pain, period pain and pain with sex in women with endometriosis when vitamin E was taken with vitamin C.

Compared with placebo [19][20][21]

Shown to make remission of premenstrual symptoms about 2.6 times as likely as placebo in women, in trials of well-described extracts.

Compared with placebo [2][3][1]; placebo, dietary supplements or other herbal preparations [3]; placebo or an active comparator [4]

Shown to ease cyclic breast pain against placebo, with a moderate effect, and to lower raised prolactin in women of reproductive age.

Compared with placebo [5]; dopamine agonists, NSAIDs, serotonin reuptake inhibitors and hormonal contraceptives [5]

Shown in one meta-analysis of 4 small trials to lower period pain more than no yoga in women with primary dysmenorrhea, with a wide margin of uncertainty.

Compared with not doing yoga [19]

Shown in one review of 14 studies to ease overall PMS symptoms and most symptom areas except physical symptoms, in trials that varied widely.

Compared with control groups the source abstract does not describe [20]

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]

Shown in one meta-analysis of 6 trials to lower period pain more than placebo, with larger effects at 8 weeks or longer.

Compared with placebo [18]; placebo or no treatment [19]

Limited evidence: unblinded trials found acupuncture shrank fibroids more than Chinese medicines or mifepristone in women with fibroids. A Cochrane review found no double-blind trials to include.

Compared with traditional Chinese medicine, and mifepristone in one trial [25]; Chinese herbal medicine alone, with acupuncture added to it [26]

One trial found satisfying sexual events rose 0.7 a month against 0.2 on placebo in premenopausal women with sexual dysfunction.

One trial found 58% of people with SSRI-related sexual problems improved on added buspirone over 4 weeks, against 30% on placebo.

One small trial found calcium alone lowered period pain 1.6 points on a 10-point scale more than placebo. Calcium with vitamin D did not differ significantly.

Compared with placebo [24]

Small trials found calcium channel blockers, mainly nifedipine, lowered birth within 48 hours in preterm labor against placebo or no treatment.

One small trial found erection hardness improved in 50% of men with mild erectile dysfunction on 1.5 g a day, against 8.3% on placebo.

One trial found a product combining D-aspartic acid, ubiquinol and zinc raised sperm motility in infertile men. D-aspartic acid's own share is unknown.

Linked to fewer repeat operations and more pain relief than excision alone in women, in observational studies. By 7 years, 77% to 92% avoided reoperation, against 45%.

Compared with laparoscopic excision with the uterus and ovaries kept [11][12]; hysterectomy with and without removal of the ovaries, against each other [11][12]

Limited evidence: total testosterone rose by a small amount in men, free testosterone did not change, and certainty was very low.

Small trials found more breast milk than placebo. In mothers of preterm infants, the day 7 difference was gone by day 15.

One small trial found PMS symptom scores fell more on ginger than placebo over 3 cycles in female students.

Compared with placebo capsules [16]

One trial found 70% still had blood loss under 80 mL after 2 years on relugolix combination therapy. After switching to placebo, 88% relapsed, at a median of 5.9 weeks.

Compared with stopping treatment by switching to placebo [4]

One small trial found green tea extract shrank fibroids by about a third over 4 months in women with symptomatic fibroids. An uncontrolled study found no size change.

Compared with placebo capsules of brown rice [13]; before treatment, in the same women [14][15]

Limited evidence: hCG-combined therapy was linked to higher pregnancy rates in men with low sperm counts or after varicocele surgery, with wide intervals.

One small trial found testosterone alone cut testicular testosterone by 94%, while adding hCG kept it near baseline at 250 to 500 IU in healthy men.

Limited evidence: in a review without controls, semen did not change in 26 men on testosterone plus hCG, and none lost sperm entirely.

One trial found testosterone rose from about 2.3 to 5.2 nmol/L on hCG, clomiphene or both in men with low testosterone, with no difference between groups.

Linked to 4.55 unintended pregnancies per 100 women a year on pills, patch or ring, against 0.27 on IUDs and implants, in a large US cohort.

Compared with IUDs and implants [1]; no comparison group in the label trials [2][3]

Limited evidence: in women with fibroids, the hormonal IUD lowered bleeding and raised hemoglobin more than the combined pill in one small trial, without clearly shrinking fibroids.

Compared with a low-dose combined pill and oral norethisterone acetate [27]; the levonorgestrel IUD and placebo [28]; comparisons in 11 studies the source abstract does not describe [29]

Small trials found period pain fell more at 12 months with a hormonal IUD placed after endometriosis surgery than with no further treatment, at low certainty.

Compared with expectant management after surgery [34]

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]

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]

Small trials found better sexual function scores than placebo in some groups, including men with mild erectile dysfunction, with no effect in healthy cyclists.

Limited evidence: four small trials reported lower menopausal symptom scores in perimenopausal and postmenopausal women.

Small trials found magnesium relieved period pain more than placebo and cut the need for extra pain medicine, in a 2001 review.

Compared with placebo [18]

Limited evidence: four tramadol trials in men found longer time to ejaculation than placebo, with high heterogeneity and more side effects.

Limited evidence: a review of 6 small trials found exercise improved pain-related quality of life in women with endometriosis, from a pooled analysis of 2 trials.

Compared with activities of daily living or conventional treatment [26]

One small trial found norethindrone acetate 5 mg and dienogest 2 mg eased endometriosis pain in women to a similar degree over 12 months, with fewer dropouts on norethindrone acetate.

Compared with dienogest [13]; dienogest, in consecutive patients before and after a clinic switched drugs [14]

One trial found purified shilajit raised total and free testosterone more than placebo in healthy men aged 45 to 55. The maker funded it.

One small study without a control group found sperm count rose 61% over 90 days in men with low sperm counts.

Limited evidence: in one clinic study, testosterone was lower with spironolactone plus estradiol than with estradiol alone, and lower still with cyproterone.

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]

One small study without placebo found higher testosterone and grip strength over 5 weeks in active adults aged 57 to 72. The maker funded it.

One pooled analysis of the two label trials found blood loss fell more than on placebo in women with fibroids, as it did in women without them.

Compared with placebo [6]

One large trial found intravenous tranexamic acid lowered death from bleeding in women bleeding after childbirth, 1.5% against 1.9% on placebo. Hysterectomy did not change.

Compared with placebo, on top of usual care [7]

Small trials found higher tumor response added to chemotherapy in women with advanced breast cancer, without placebo. A stomach trial measured markers, not cancer.

Limited evidence: symptom scores fell about 50% after MRI-guided focused ultrasound in pooled studies with no comparison treatment, and quality of life improved.

Compared with before treatment, in the same women [11][12]

One trial found slightly higher infant mental development scores at 250 µg than at 50 µg a day in vegetarian pregnant women in India and Nepal.

One uncontrolled study by the manufacturer found most women reported lighter, less frequent bleeding and less period pain after 3 months, with no comparison group.

Compared with before treatment, in the same women [7]