Summary
With the increase in health and life expectancy, the number of menopausal women has increased significantly. In parallel, there has been a reduction of birth rates influenced by women having their first maternity in an advanced age. Both trends have an impact on national demographics and impose a socioeconomic challenge for which there is no current solution. Women with symptomatic menopause and those with infertility/miscarriage may take advantage of standard therapies such as menopause hormone therapy (MHT) or in vitro fertilization, respectively. Although these interventions are effective, both are expensive, have low yield, and not free of controversial issues. As women age, the output of ovarian steroids and competent oocyte availability approach unrecoverable loss beyond the age of 35 years, no matter the treatment. Currently there is interest in native sex steroid rejuvenation, de novo euploid oogenesis, ovulation, blastocyst development, fetal growth, and healthy term livebirths-all apparently possible with intraovarian insertion of platelet-rich plasma (PRP). Discrete functional analysis of the full platelet-derived cytokine array carried with PRP, unfortunately for now, is incomplete. Here, the release of constituents of selected platelets and measured effects are framed to address advances in wellness and women’s health. Emphasis is on cytokines best positioned to enable recovery of senescent ovarian function sufficient to suspend synthetic MHT dependency and/or permit egg retrieval and pregnancy.
Commentary
In this commentary I would like to focus on an interesting review article written by Scott Sills [1] that discusses the application of condensed cytokines to reverse reproductive aging. The author states that infertility and menopause are both closely related to ovarian reserve. Further efforts need to be developed to improve ovarian function, which is safe and effective and, if possible, without synthetic drugs, so that it helps overcome the problems of the two condi-tions above mentioned [1].
Ovarian rejuvenation using autologous PRP injected into the ovaries is one of several options. Platelets, as a main component of PRP, contain more than 1,100 different proteins, including immune system messengers, growth factors, enzymes and other factors which can participate in tissue repair and wound healing [2].
The commented article mentions that PRP treatment seems better suited to address infertility than for menopause treatment, as most patients would probably regard PRP as impractical and uncompetitive against MHT. Agreeing with that opinion, but slightly different, Pantos et al. reported two cases of women with premature ovarian insufficiency (POI) and one meno-pausal woman who had failed IVF, and in subsequent cycles were given autologous ovarian PRP treatment. The outcome of the cases were the restoration of menstruation, as well as an improvement in the hormonal profile. In a subsequent report, the three women achieved preg-nancy through natural conception within 2-6 months post-treatment [3]. In addition, in a ret-rospective observational study involving 469 POI women who were given PRP treatment (2-4 mL per ovary), the results showed a significant improvement in the normal values of FSH and E2 that were observed for three and four months after treatment [4].
In menopausal women, oxidative stress is thought to be involved which affects fertility. Menopause creates a systemic pro-oxidant state due to decreased production of estrogen [5]. In addition, menopause is also associated with an inflammatory environment, decreasing es-trogen levels, followed by increased activity of pro-inflammatory cytokines IL-6, IL-4, IL-2, TNF- [6]. Jiao et al. [7] proved in their study that PRP can significantly suppress malonic dialdehyde (MDA) and increase superoxide dismutase (SOD) activity, thereby improving the oxidative stress environment. Abdul Ameer et al. [8] in their study, PRP therapy proved to reduce lymphocyte concentrations, through the production of RANTES, which inhibits the release of cytokines and suppresses the concentration of Lipoxin A4 (anti-inflammatory marker) and in turn inhibits the activation of inflammatory factors.
The method of preparing PRP is in continuous development using condensed cytokines iso-lated after in vitro platelet incubation/processing with the aim of increasing growth factors and cytokines. Garavelas et al. [9] reported a study of PRP treatment with a two-step centrif-ugation method on the rejuvenation of ovarian function. PRP improved hormone profiles and 17% of the women in this pilot study successfully conceived.
From the data stated above, PRP seems to be an interesting therapeutic option that can poten-tially reverse reproductive aging, but we still need to be careful because there is no consensus on optimal component concentrations. PRP treatment can also improve complaints of the gen-itourinary syndrome of menopause, as well as improve ovarian function and fertility problems [10]. Although PRP has been used widely, there is still a need for future randomized clinical trials to provide strong evidence for its use in ovarian rejuvenation and before offering it rou-tinely in clinical practice.
Hendy Hendarto, MD, PhD
Department of Obstetrics and Gynecology Faculty of Medicine, Universitas Airlangga – Dr. Soetomo Academic General Hospital, Surabaya,
PERMINASIA-Indonesian Menopause Society
References
- Sills ES. Ovarian recovery via autologous platelet-rich plasma: New benchmarks for condensed cytokine applications to reverse reproductive aging. Aging Med (Milton). 2022;5(1):63-67.
https://pubmed.ncbi.nlm.nih.gov/35309160/ - Pavlovic V, Ciric M, Jovanovic V, Stojanovic P. Platelet Rich Plasma: a short overview of certain bioactive components. Open Med. 2016;11(1):242–247.
https://pubmed.ncbi.nlm.nih.gov/5329835/ - Pantos K, Simopoulou M, Pantou A, et al. A Case Series on Natural Conceptions Resulting in Ongoing Pregnancies in Menopausal and Prematurely Menopausal Women Following Platelet-Rich Plasma Treatment. Cell Transplantation. 2019;28(9-10):1333–1340.
https://pubmed.ncbi.nlm.nih.gov/31271054/ - Fraidakis M, Giannakakis G, Anifantaki A, et al. Intraovarian Platelet-Rich Plasma Injections: Safety and Thoughts on Efficacy Based on a Single Centre Experience With 469 Women. Cureus. 2023;15(5):e38674.
https://pubmed.ncbi.nlm.nih.gov/37288228/ - Bourgonje AR, Abdulle AE, Al-Rawas AM, et al. Systemic Oxidative Stress Is Increased in postmenopausal women and independently associates with homocysteine levels. Int J Mol Sci. 2020;21(1):314.
https://pubmed.ncbi.nlm.nih.gov/31906485/ - Pfeilschifter J, Koditz R, Pfohl M, Schatz H. Changes in proinflammatory cytokine activity after menopause. Endocr Rev. 2002;23(1):90-119.
https://pubmed.ncbi.nlm.nih.gov/11844745/ - Jiao Y, Zhang Q, Zhang J, et al. Platelet-rich plasma ameliorates lipopolysaccharide-induced cardiac injury by inflammation and ferroptosis regulation. Front Pharmacol. 2022;13:1026641.
https://pubmed.ncbi.nlm.nih.gov/36330090/ - Abdul Ameer LA, Raheem ZJ, Abdulrazaq SS, Ali BG, Nasser MM, Khairi AWA. The anti-inflammatory effect of the platelet-rich plasma in the periodontal pocket. Eur J Dent. 2018;12(4):528–531.
https://pubmed.ncbi.nlm.nih.gov/30369798/ - Garavelas A, Mallis P, Michalopoulos E, Nikitos E. Clinical Benefit of Autologous Platelet-Rich Plasma Infusion in Ovarian Function Rejuvenation: Evidence from a Before-After Prospective Pilot Study. Medicines (Basel). 2023;10(3):19.
https://pubmed.ncbi.nlm.nih.gov/36976308/ - Merlino L, D’Ovidio G, Matys V, et al. Therapeutic Choices for Genitourinary Syndrome of Menopause (GSM) in Breast Cancer Survivors: A Systematic Review and Update. Pharmaceuticals (Basel). 2023;16(4):550.
https://pubmed.ncbi.nlm.nih.gov/37111307/
If you would like to add a comment or contribute to a discussion based on this issue, please contact Menopause Live Editor, Peter Chedraui, at peter.chedraui@cu.ucsg.edu.ec.
