Table 2.

Phytoestrogens and Pelvic Organ Prolapse Studies

Study	Design	Intervention	Comparison	Duration	Outcomes	Results
Tomaszewski (2009)[32]	In vitro	Pubocervical fascia (PCF) obtained from a 56 yr old woman with SUI and POP	Same as intervention group but without mesh exposure	Collagen type I (Col I) biosynthesis was assessed after 48, 96, and 144 hrs	Biosynthesis of aminoterminal propeptide of type I procollagen as a marker of Col I biosynthesis in cultured PCF fibroblasts	Fibroblasts from PCF taken from a menopausal woman with SUI and POP are capable of Col I biosynthesis after estrogen and phytoestrogen treatment.
Abstract in English		PCF fibroblasts cultured with mono- or multifilament mesh and exposed to 17β-estradiol (E2), estriol or phytoestrogen daidzein				There was decreased fibroblast biosynthesis of aminoterminal propeptide of type I procollagen in the study subgroup using multifilament polypropylene mesh. The most significant difference between assessed groups was recorded within the 96th and 144th hour. It is possible that decrease of collagen type I biosynthesis after 144 hours of the experiment was caused by aging of the culture (no p-value).
Full text in Polish
						Summary: Col I levels in cultured PCF fibroblasts taken from a 56 yo menopausal woman with SUI and POP increased after exposure to estrogen and daidzein.
Tomaszewski (2010)[33]	In vitro	Pubocervical fascia (PCF) obtained from a 56 yo woman with SUI and POP	Skin fibroblasts	Cultures were run for 216 hrs and the media were replaced every 72 hrs	Procollagen type 1 N-terminal propeptide (PINP) as a marker of Col I synthesis by PCF fibroblasts cultured with mono- or multifilament polypropylene mesh in the presence of estrogens and a phytoestrogen	Fibroblasts exposed to estriol or daidzein produced more Col I than those treated with estradiol regardless of the mesh applied.
Abstract in English		PCF fibroblasts cultured with mono- or multifilament mesh and exposed to 17β-estradiol (E2), estriol or phytoestrogen daidzein				In the presence of monofilament mesh, peak PINP concentration increased persistently with estriol and daidzein throughout the study whereas the peak PINP was between 72-144 hrs for estradiol.
Full text in Polish						In the presence of multifilament mesh, the rate of Col I production dropped after 144 hrs in all cultures.
						No data available in abstract.
						Summary: PCF fibroblasts produced more Col I when exposed to estriol or daidzen regardless of the type of vaginal prolapse mesh applied.
Tomaszewski (2010)[34]	In vitro	Pubocervical fascia (PCF) obtained from a 52 yo premenopausal woman undergoing SUI surgery	PCFs without treatment	Cultures were run for 216 hrs and the media were replaced every 72 hrs	N-terminal propeptide of type III procollagen (PIIINP) as a marker of collagen type III (Col III) synthesis by PCF fibroblasts cultured with mono- or multifilament polypropylene mesh in the presence of estrogens, a phytoestrogen, and an anti-estrogen	High collagen type III synthesis persisted throughout the study period only in cultures containing monofilament mesh stimulated with estriol. The highest total PIIINP production was observed in culture treated with tamoxifen regardless of mesh types.
Abstract in English						No data available in abstract
Full text in Polish		PCF fibroblasts cultured with mono- or multifilament mesh and exposed to 17β-estradiol (E2), estriol, phytoestrogen daidzein, or tamoxifen				Summary: Col III only showed a persistent increased production by PCF fibroblasts in cultures containing monofilament mesh stimulated with estriol. The highest total Col III production was observed in culture treated with tamoxifen regardless of the type of mesh.
Iwanaga (2016)[35]	In vitro and animal, mice	For human subjects: Oxytocin receptor (OXTR) mRNA expression in human USL collected from 11 premenopausal women with normal pelvic support (controls, CTL) vs. 6 premenopausal women with POP vs. 7 postmenopausal women with POP.		Up to 70 week old mice	For human subjects: Oxytocin receptor (OXTR) mRNA expression in human USL	For human subjects: OXTR expression was decreased by 65% in the premenopausal POP group and by 78% in the postmenopausal POP group (both p<0.05) compared to premenopausal CTL.
Abstract only		For mice; OXTR expression was compared between mice with prolapse and age-matched mice without prolapse (n=3 and 10, respectively) Ovx mice for 2 months (nulliparous or NP, n=6, multiparous or MP, n=6) Ovx mice for 2 months further treated with and without 2-day estradiol treatment (n=5 and 6, respectively) 12 months mice undergoing sham surgery and treated with vs. without 2-day estradiol treatment (n=5 and 6, respectively) 70 weeks old NP mice raised on a phytoestrogen diet (n=10) vs. phytoestrogen-free diet (n=10)			For mice: OXTR expression was compared in mice USL i)with vs. without prolapse ii)Ovx in NP and MP mice vs. sham surgery iii & iv) with vs. without E2 treatment to sham and OVX mice v)phytoestrogen diet vs. phytoestrogen-free diet	For mice: OXTR was decreased by 90% in mouse USL with POP compared to CTL (p<0.05). OVX resulted in significantly decreased OXTR expression in NP and MP mice compared to sham (p<0.05)*. Treatment with E2 to a MP sham and OVX mice increases expression of OXTR (p<0.05)*. Phytoestrogen diet had a significant impact on OXTR expression in USL compared to phytoestrogen free diet (p<0.05)*.
						*no specific data available in abstract.
						Summary: Both estradiol and a phytoestrogen diet increased expression of OXTRs and had a significant impact on OXTR expression in the USL.
Jiang (2017)[36]	Prospective cohort of women having transvaginal surgery for POP and/or SUI	Puerarin 0.429 mg/day for 30 days, n=30	Placebo for 30 days, n=22	June 2010 to Nov 2012	POP symptoms: non-validated score based on POP-Q exam (positive or strongly positive improvement in symptoms if 1+ or 2+ stage improvement, respectively)	Patients treated with puerarin had significant improvement of POP vs. control patients (positive: 57 % vs. 0%, and strongly positive 35% vs. 0%, p<0.05). Elastin positive rate (9.8% ± 2.8% vs 2.8% ± 1.3%, p<0.05), collagen I/III ratio (1.1 ± 0.3 vs 0.5 ± 0.3, p<0.05), NPY, VIP and TGF-β was significantly increased in the puerarin group compared to control (all p<0.05).
Full text					Vaginal tissue: biopsies of participants’ prolapsed tissue obtained.
					Expression of elastin, collagen, neuropeptide Y (NPY), vasoactive intestinal polypeptide (VIP) and transforming growth factor beta (TGF-β) was evaluated in all patients using immunohistochemistry	Summary: After 30 days, women treated with puerarin had significant improvement of POP. The expression of elastin positive rate and collagen I/III ratio were significantly increased in the puerarin group. NPY, VIP, and TGF-β levels were also significantly increased.