Table 2 Effects of VAC preparations in placebo controlled clinical studies on PMS, PMDD, and premenstrual mastodynia

Milewicz et al., 1993 [22]

Randomized, placebo controlled trial

11 VAC extract. 11placebo treated women with PMS and latent hyperprolactinemia, mean age 30 y

20 mg of an extract of VAC dried fruits (Strotan) for 3 months

PMS. Basal and TRHstimulated prolactin, lutael phase progesterone

Reduction of PMS in 9 verum but only in 2 placebo treated women

+

Turner et al., 1993 [21]

Randomized, double blind placebocontrolled trial

600 verum, 217 soy based placebo. age 18–46 y

3×600 mg/day of a not defined VAC extract, 3 months

Moos Menstrual Distress Questionnaire

No significant effects on all but one item placebo effects better than verum, note however, the extremely high dose

Ø

Lauritzen et al., 1997 [23]

Randomized, double blind. comparatorsudy

46 VAC. 57 pyridoxine treated women with PMS, 18–45 y

3.5–4.2 mg dried VAC extract (Agnolyt) vs pyridoxine, 3 cycles

PMS was measured by VAS premenstrual Tension Scale

Significant “excellent” reduction of PMS superior to pyridoxine

+

Schellenberg et al., 2001 [26]

Randomized, double-blind, placebocontrolled

170 women with PMS Mean age 36 y

86 VAC, 84 placebo treated women with PMS, 3 cycles

20 mg of a VAC extract Ze 440,

Significant reduction of all symptoms in comparison to placebo (except bloating)

+

Wuttke et al. 1997 [24]

Randomized, double-blind, placebocontrolled

104 patients with premenstrual mastodynia determined by VAS

66 patients treated with 40 mg dried fruit VAC, 38 placebo, 3 cycles

Visual analogue score of mastodynia

Significantly better improvement of mastodynia under both VAC peparations

+

Halaska et al. 1999 [25]

Randomized, double-blind, placebo controlled

97 patients with premenstrual mastodynia determined by VAS

48 patients with dried VAC fruit, 49 with placebo, 3 cycles

Visual analogue score of mastodynia

Significantly better reduction of mastodynia under VAC

+

He at al., 2009 [29]

Randomized, double-blind, placebocontrolled trial

101 women verum vs 101 placebo for 3 cycles

40 mg dried fruit powder (equivalent to 4 mg dried extract vs placebo

Moderate to severe forms of PMS assessed by DSM IV and PMTS score greater than 18

Significantly greater improvement under VAC (80%) than under placebo (50%)

+

Ma et al., 2010 [31]

Randomized, double blind, placebo controlled trial

31 women with verum vs 33 women under placebo, 3 cycles

40 mg dried fruit powder vs placebo given during luteal phase

PMSD score greater 16 points

Significantly greater improvement under VAC (85%) vs placebo (56%)

+

Kilicdag et al., 2004 [27]

Randomized, double blind comparator controlled trial

40 women with mastodynia and 40 women with latent hyperprolactinemia

2×40 mg dried fruit vs 2×2.5 bromocriptine daily for 3 months

Breast discomfort by VAS

Both treatments were similarly effective Fewer side effects under VAC

+

Gumenyuk (2010) [45]

Randomized oprn 3 months

31 with PMS 19 of them PMDy

40 mg VAC(Mastodynon)

PMS, mastodynia, prolactin

Significant reduction of all parameters

+

Pakgohar et al., 2009 [30]

Randomized, double-blind, placebocontrolled,

39 women with verum, 50 with placebo

4.3–4.8 mg dried VAC extract vs placebo

PMS diagnosed by general practitioner

Improvement significantly better under VAC (61%) vs placebo (29%)

+

Ciotta et al., 2011 [33]

Randomized, double blind, comparator controlled

31 women under verum vs 26 under fluoxetine, 2 months

20 mg dried fruit powder vs 20–40 mg fluoxetine

DSM IV criteria for severe PMS

Both treatments improved symptoms significantly with better outcome for fluoxetine

+

Zamani et al., 2012 [34]

Randomized, double-blind, placebocontrolled trial

62 verum vs 66 women under placebo for 6 days prior to expected menstrual bleeding for 6 cycles

40 drops of an undefined VAC extract vs placebo

Selection by DSM IV criteria i

Significantly better effects for all items under VAC in comparison to placebo

+

Schellenberg et al. 2012 [35]

Randomized, double-blind, placebo controlled,

4 groups of women (3 verum. Vs placebo) with PMS, 18–45 y

8, 20 and 30 mg drie VAC fruit vs plavebo40 mg VAC dried fruit (Mastodynon) vs placebo

Premensrual mastodynia i

Dose dependent significant reduction of mastodynia

+

Malykhina 2006 [28]

Randomized single-blind, comparator controlled

120 women with mastalgia and latent hyper-prolactinemia divided in 3 groups

2.5 mg bromocriptine, 0.25 mg Dostinex, 40 mg dried fruit VAC (Agnucaston) all given for 3 months

Mastalgia and latent hyperprolactinemia

Breast pain absent within 2 weeks in all 3 groups. Normalization of prolactin at the end of the study in all 3 groups

+

Suturina and Popova, 2010 [32]

Randomized, single-blind, comparator controlled

2 goups of women (24 in each group) after intensive gynecologic check up

40 mg of dried VAC fruit (Cyclodynon) vs 2.5 mg bromocripitine, twice daily for 3 months

Questionnaire and serum prolactin

Significant reduction of mastalgia in both groups, Cyclodynon improved symptoms in all bromocriptine only in 16 patients,

+

Tuganbekov and Oralbay 2012 [46]

Non randomized, prospective study, 2 monnths

30 women with fibrocystic mastopathy with mastodynia

40 mg VAC dried fruit (Mastodynon)

Changes in fibrocystic appearance, serum prolactin, TSH and estradiol

Significant (90%) reduction of fibrocystic appearance, mastodynia and prolactin

+

Ledina and Prelipskaya 2011 [36]

Randomized. 2 months

50 women with mastalgia

1 group (n = 30) with VAC, the other with an COC (n = ` 20)

Visual analogue scale

Significant effects of both treatments VAC > than COC

+

v Kubista et al. 1986

Randomized, double-blind trial vs placebo and a progestin

38 verum vs 28 progestin vs 55 placebo

VAC 1095 (Mastodynon) vs a progestin vs placebo

Mastodynia, often in combination with fibrocystic mastopathy

Reduction under progestin 89%, under VAC 74% and under placebo 37%

+