A new treatment of genito-urinary post-menopausal atrophy with autologous micro-fragmented fat tissue: a thirty-six months follow up case series.

OBJECTIVE: Genitourinary atrophy is a menopausal pathological change determined by the definitive drop of ovarian hormones' production that can impact heavily on the health status of women, with important direct and indirect social costs. Unfortunately, available treatments are only symptomatic, and they are not able to reverse the atrophy and other related symptoms. Regenerative medicine, with single local injection of autologous micro-fractured fat tissue, could represent a viable new solution for these patients as it not only helps to relieve symptoms, but it also counteracts the mechanisms that lead to the menopausal genitourinary atrophy. The objective of this paper is to evaluate the long-term effectiveness of micro-fractured fat vulvar injection for genito-urinary atrophy in patients, affected by severe genitourinary atrophy (at least 4 symptoms lasting for at least 4 years). PATIENTS AND METHODS: We present a case series of 35 patients followed for 36 months to evaluate the effectiveness and safety of a single subcutaneous vulvar injection of autologous micro-fragmented fat tissue (MFAT). RESULTS: We have not observed any adverse effects in any patients. All symptoms, and especially pelvic pain and dyspareunia, improved in almost half of patients within 3 months. Ninety-nine percent of patients recovered completely from all symptoms after 9-12 months, reporting no relapse of the symptoms up to the third year of follow up. CONCLUSIONS: Our case series is the first case series, evaluating the long-term (3 years) safety and effectiveness of micro-fragmented adipose tissue graft for urogenital atrophy.

Menopause: new frontiers in the treatment of urogenital atrophy.

OBJECTIVE: Urogenital atrophy is a degenerative process that may occur during menopause causing debilitating disorders and painful symptomatology. Estrogen therapy slows the onset of atrophy, but it requires ongoing therapy to maintain its effectiveness. To mitigate the degenerative evolutions associated with menopause, patients may benefit from new therapeutic approaches, such as the use of mesenchymal stem cells. Among the many sources, the adipose tissue is considered one of the smartest, due to its abundance and easy access. This study investigated the feasibility and potential benefits of using an autologous adipose tissue to treat the symptoms of urogenital atrophy. PATIENTS AND METHODS: In 2014, the first three women affected by post-menopausal urogenital atrophy were treated with injections of autologous and micro-fragmented adipose tissue (Lipogems®). Clinical outcomes were determined at 3, 6, 9, 12, 18, 24, and 36 months by evaluating vaginal dryness, burning, itching, stranguria, sensitivity, and dyspareunia. Pre- and 36 months post-op biopsies and vaginal discharge were also collected. RESULTS: The three women reported a significant improvement of the symptoms at 6 months with complete resolution at 9 months. This benefit, subjectively reported and confirmed by clinical evaluation, remained constant without recurrence at least until 36 months. Immunohistochemical analysis revealed a total recovery of vaginal vitality with production of glycogen, vasculature hyperplasia and regeneration of the epithelium and subcutaneous tissue at 36 months. The analysis of vaginal discharge showed a restoration of an acid pH with the colonization of lactobacilli. No postoperative complications nor adverse events were recorded. CONCLUSIONS: The results of these first three cases pointed to autologous and micro-fragmented adipose tissue as a safe, feasible and effective therapeutic approach for the treatment of post-menopausal urogenital atrophy.

Estro-progestinic replacement therapy modulates the levels of basic fibroblast growth factor (bFGF) in postmenopausal endometrium.

The levels of basic fibroblast growth factor (bFGF) in human endometrium do not vary during the ovulatory cycle but they increase significantly after menopause (M. Rusnati et al., Growth Factors, 3, 299-307, 1990). Here we report that cyclic estro-progestinic replacement therapy reduces the levels of bFGF in human postmenopausal endometrium to those measured in ovulatory cycle endometrium. Also, we have observed that the levels of bFGF in well-differentiated adenocarcinomas of the endometrium from postmenopausal patients are lower than those detected in their normal counterpart and are comparable to those measured in the normal cycling tissue. The data indicate that the stimulation of cell proliferation induced in postmenopausal endometrium by hormonal therapy or by neoplastic transformation is paralleled by a decrease of endometrial levels of bFGF. This may be due to an increase of the turnover rate of the growth factor in the proliferating versus the quiescent tissue and suggests a role of bFGF in the growth of normal and neoplastic human endometrium. Our data represent the first evidence that sex hormones modulate the levels of biologically active bFGF in vivo.

Basic fibroblast growth factor in ovulatory cycle and postmenopausal human endometrium.

Biopsies of human endometrium were studied for the presence of basic fibroblast growth factor (bFGF). An immunoreactive Mr 18,000 bFGF-like molecule was detected at high levels both in ovulatory cycle and postmenopausal endometrium. This molecule was identified as bFGF on the basis of its molecular weight, its affinity for heparin, its capacity to induce plasminogen activator production and cell proliferation in endothelial GM 7373 cells, and its cross-reactivity with various anti-bFGF antibodies. The levels of endometrial bFGF do not change during the menstrual cycle but they increase significantly after menopause, as evaluated both by biological and immunological assays. Lower levels of an acidic FGF-like activity were also evident in ovulatory cycle endometrium but, at variance with bFGF, no significant increase of this activity was observed in postmenopausal endometrium. These data represent the first characterization of a polypeptide growth factor present in human endometrium.