Polycystic Ovary Syndrome (PCOS): Current and Future Therapy - International Journal of ...
←
→
Page content transcription
If your browser does not render page correctly, please read the page content below
International Journal of Science and Healthcare Research
Vol.5; Issue: 3; July-Sept. 2020
Website: ijshr.com
Review Article ISSN: 2455-7587
Polycystic Ovary Syndrome (PCOS): Current and
Future Therapy
Maged MN1, Mohamed MN2, Lamia H.Shehata3
1
Mazahmiya Hospital, Ministry of Health, Kingdom of Saudi Arabia.
2
Department of Ob/Gyn, King Fahd Hospital, Ministry of Health, Kingdom of Saudi Arabia.
3
Department of Surgery, Care National Hospital, Kingdom of Saudi Arabia.
Corresponding Author: Maged MN
ABSTRACT mixes of signs and manifestations, which
may incorporate conceptive, endocrine, and
Polycystic ovary syndrome (PCOS) is a metabolic adjustments. PCOS is portrayed
multifaceted condition portrayed by constant by hypothalamic–pituitary–ovary axis
anovulation and excess ovarian activity, as dysfunction and anovulation in any case,
opposed to different reasons for anovulation that
dissimilar to different reasons for ovulatory
include ovarian lethargy or essential
inadequacy. Ongoing examinations showed that failure that highlight inadequate ovarian
PCOS is related with second rate ceaseless follicle development or suppressed
aggravation and that women with PCOS are at gonadotropin secretion (or both), PCOS
expanded danger of non-alcoholic fatty liver commonly incorporates androgen
disease. The inflammatory and metabolic overabundance and inconspicuous
disturbances related with PCOS are clarified to adjustments (not identified by routine tests)
some extent by the conjunction of insulin in serum levels of gonadotropins and
resistance and obesity however are additionally estrogens. PCOS has the potential for
filled by the androgen abundance. New bits of serious outcomes, including expanded
knowledge into the guideline of hormones and hazard for the advancement of endometrial
cytokines in muscle and fat tissue bolster the
hyperplasia and neoplasia (1). Moreover,
idea that PCOS is a foundational condition. The
therapeutic arrangement ought to be customized extra-conceptive appearances of PCOS
to the patient phenotype, complaints, and incorporate insulin resistance (IR),
reproductive desire. Of note, the aromatase metabolic syndrome (MS), and low-grade
inhibitor letrozole is by all accounts more chronic inflammation (2–6).
powerful than the reference medicate Lately, numerous advances have
clomiphene citrate to treat barrenness due to been made in the under-remaining of
PCOS. Fundamental administration by a pathophysiological components and
multidisciplinary team may help the patients to subsequently in the diagnosis and the
adhere to lifestyle interventions and in this way management of PCOS.
lessen body adiposity and recuperate their Advances and difficulties in PCOS
metabolic and reproductive health.
understanding The Rotterdam Consensus,
Key words: Polycystic ovary syndrome, PCOS, held mutually by the European and the
insulin resistance, infertility, menstrual North American relationship of regenerative
irregularity medication in 2003, characterized the
diagnostic rules of PCOS which remain the
INTRODUCTION most utilized worldwide for both individual
Polycystic ovary condition (PCOS) analysis and research. It characterized
is the most widely recognized endocrine PCOS as the nearness of any two of three
issue in women, giving a few potential highlights: hyperandrogenism (clinical or
International Journal of Science and Healthcare Research (www.ijshr.com) 202
Vol.5; Issue: 3; July-September 2020Maged MN et.al. Polycystic ovary syndrome (PCOS): current and future therapy
biochemical), ovulatory dysfunction light of the fact that the test strategies are
(menstrual abnormalities), and polycystic inadequately normalized, there are no
ovarian morphology (PCOM) by ultrasound. general shorts for conclusion, and a few
The syndrome is a finding of exclusion that measures with the expectation of
ought to be built up simply after assessment complimentary testosterone evaluation are
of different reasons for anovulation or unreliable(13,14). In this manner, until a
androgen abundance (or both): delicate, reproducible, and broadly approved
hypogonadism, hypo-or hyperthyroidism, testosterone test opens up and reasonable for
hyperprolactinemia, 21-hydroxylase clinical practice, the evaluation of
deficiency, Cushing's condition, and biochemical hyperandrogenism to affirm or
androgen-creating tumors(7). In spite of discard PCOS ought to depend on complete
some contention about the suitability of the serum testosterone, sex hormone–binding
Rotterdam rules to manage PCOS globulin (SHBG), and free androgen index
medicines, their utility to anticipate using local cutoffs(13,15).
regenerative results is well established (8). Anti-Müllerian hormone (AMH) is a
An ongoing rule from the International glycoprotein emitted by the granulosa cells
PCOS Network suggested utilization of the of pre-antral and small antral follicles.
Rotterdam measures in grown-ups and the AMH assumes a fundamental role in sexual
necessity of both oligo-anovulation and differentiation and gonadal function, other
hyperandrogenism for PCOS analysis in than focal consequences for the
adolescents(9). hypothalamic–pituitary–gonadal axis. A
There are a few mixes of signs and direct test study showed that AMH receptor
symptoms that might be represented in the is communicated in gonadotropin-releasing
diagnosis of PCOS, bringing about various hormone (GnRH) neurons and that intra
phenotypes for a similar syndrome. To all cerebroventricular organization of AMH
the more likely comprehend the expands GnRH-subordinate luteinizing
pathogenesis of the disorder, it is critical to hormone (LH) pulsatile release (16). There
analyze the genetic profiles of women is collecting proof that GnRH pulsatility is
whose finding depended on the various perturbid in women with PCOS, prompting
phenotypes. An ongoing genome-wide expanded LH pulsatility, which plays a
meta-investigation from more than 10,000 significant role in PCOS
PCOS cases distinguished 14 free loci pathophysiology.(17) Serum AMH levels
related with the hazard for PCOS, including are ordinarily expanded in PCOS(18), and
three novel loci (10). This huge scope study subsequently AMH-subordinate guideline of
found no contrast between the different GnRH discharge could be associated with
clinical phenotypes for the relationship with the patho-physiology of richness in women
the greater part of the PCOS susceptibility with PCOS.(16)
loci, proposing that normal genetic traits
may underlie the different phenotypes. I. Metabolic profile
Hyperandrogenism is a significant IR is so regular in PCOS that it very
clinical characteristic of the condition since well may be viewed as an indispensable part
it is related with more worse prognosis and of the syndrome. IR and glucose
higher risk of metabolic and cardiovascular metabolism deregulation are right now
disease (11). Be that as it may, late genetic expected to assume a pathogenic role in the
discoveries recommend that it may not be disease. IR prompts compensatory
the main driver of PCOS manifestations hyperinsulinemia, which increments ovarian
(10,12). As analyzed by the Rotterdam androgen synthesis both by direct ovarian
rules, hyperandrogenism is available in activities and by animating LH secretion.(3)
around 60 to 80% of cases. Biochemical IR likewise actuates dyslipidemia, and
hyperandrogenism stays an analytic test in women with PCOS have an expanded risk
International Journal of Science and Healthcare Research (www.ijshr.com) 203
Vol.5; Issue: 3; July-September 2020Maged MN et.al. Polycystic ovary syndrome (PCOS): current and future therapy
of type(2) diabetes mellitus and impacts of vigorous exercise (24) and
cardiovascular disease .(5) shields the cerebrum from synaptic and
Another expected metabolic cognitive decline in a creature model of
inconvenience of PCOS is non-alcoholic Alzheimer's disease (25). Moreover, in vivo
fatty liver disease (NAFLD), characterized irisin imbuement improves bone mass and
as hepatic steatosis is not clarified by engineering in youthful male mice (23).
alcohol or other specific etiologic agents. The declaration of Irisin is
NAFLD is mechanistically and emphatically connected with body mass
epidemiologically connected to obesity, IR, index (BMI) and muscle mass, and Irisin
and MS(19). PCOS is related with expanded metabolism is abnormal in patients with
risk of NAFLD paying little heed to the type 2 diabetes or gestational diabetes (26).
nearness of heftiness, proposing that the Serum Irisin levels were related with
connection among PCOS and NAFLD is hyperandrogenism yet not with
likewise clarified by different highlights of oligovulation or PCOM in women with
PCOS, for example, IR and androgen PCOS(27). After modification for BMI,
abundance. Truth be told, a deliberate audit patients with PCOS appear to have typical
and meta-investigation demonstrated a Irisin levels; in any case, Irisin reaction to
higher predominance of NAFLD among hyper insulinemia may be impaired in
women with hyperandrogenic PCOS patients with PCOS(28).
contrasted and different phenotypes of the It is dubious whether PCOS is some
disorder, while serum androgen levels were way or another related with low serum
higher in PCOS women with NAFLD levels of nutrient D. A precise audit
contrasted and PCOS ladies without discovered 12 studies with heterogeneous
NAFLD.(20) outcomes and their meta-investigation
Adipokines and inflammation go proposed lower serum 25-(OH) D in PCOS
betweens discharged by the fat tissue versus controls yet no distinctions in serum
likewise add to the metabolic modifications 1,25 (OH) D between the two groups(29).
found in PCOS(6) Furthermore, various All the more critically, if a woman with
development elements, cytokines, and PCOS has nutrient D insufficiency, she will
receptive oxygen species delivered by the be at expanded risk of metabolic
ovaries, liver, and different tissues make a comorbidities. Nutrient D supplementation
condition of interminable inflammation that may lessen ceaseless inflammation markers
agrees to keep up the metabolic in women with PCOS and nutrient D
awkwardness of the syndrome(4,6) deficiency (30,31), yet there is no proof that
During the previous decade, skeletal such treatment improves the metabolic
muscle has likewise been recognized as a status of patients(29)
secretory organ that releases cytokines and Polycystic ovarian morphology
different peptides, called myokines. Irisin (PCOM) and the finding of PCOS, PCOM is
has been distinguished as an exercise one of three models for determination of
induced myokine and has been proposed to PCOS. PCOM is characterized as follicle
intercede the valuable impacts of activity on number, be that as it may, the most recent
metabolism (21). Irisin can incite an age of ultrasound gadgets (maximal test
adjustment in attributes of white adipocytes frequencies that surpass 8 MHz) is
that secure a "brown" phenotype. This increasingly delicate and yields a bigger
change incorporates the initiation of follicle include in everybody; in this
uncoupling protein 1 (UCP-1), prompting manner, the current utilization of the old
expanded breath and vitality expenditure cutoff can overestimate the commonness of
(21,22) Irisin is additionally delivered at PCOM(32). A gathering of specialists as of
lower sums outside the skeletal muscle(23). late proposed the utilization of higher in-
Mind inferred Irisin intercedes anxiolytic house edges (that is, 19 to 25 follicles for
International Journal of Science and Healthcare Research (www.ijshr.com) 204
Vol.5; Issue: 3; July-September 2020Maged MN et.al. Polycystic ovary syndrome (PCOS): current and future therapy
each ovary) to characterize PCOM with the PCOS in adolescence: Menstrual
new ultrasound machines (33). irregularity, acne, and hirsutism are the
significant discoveries in this age gathering.
Serum AMH levels associate with Be that as it may, these highlights of PCOS
follicle number in women with PCOS. A cover with those of ordinary adolescence.
few investigations found a decent Family history of PCOS, overweight or low
concordance between serum AMH levels birth weight, exposure to androgens during
and ultrasound results for the determination gestation, precautious puberty, obesity, and
of PCOM. These investigations propose that IR are hazard factors that are identified with
serum AMH could be an intermediary for the advancement of the disorder. The
ovarian follicle count and an elective marker determination of PCOS during adolescence
of PCOM to be utilized reciprocally with depends on stricter rules than in adult
ultrasound relying upon serum AMH and women. It requires unequivocal
ovarian follicle check availability (34). hyperandrogenism (for instance, moderate
Ongoing investigations show that elevated to extreme hirsutism or persevering height
levels of AMH (>35 pmol/L) have a decent of serum testosterone levels or both) and
connection with the finding of PCOM at ovulatory dysfunction that continues for
ultrasound (34). In any case, serum AMH more than 2 years after menarche (36).
levels ought not yet be utilized as a marker Ongoing examinations indicated that
or as a solitary test for the analysis and adolescents with PCOS have expanded
recognition of PCOS (9, 33). danger of MS and ought to be encouraged to
embrace a sound way of life at once (37). At
II. PCOS at various phases of life the point when an analysis of PCOS has
An investigation thought about been built up, the chance of IR signs and
clinical and biochemical boundaries of quality of life issues ought to be thought of.
PCOS in women and controls that visited a Weight, overweight, and hyperinsulinemia
clinical focus at a mean age of 29 years and might be available in young people.
returned 6 years after the fact all things Furthermore, dietary issues (bulimia,
considered. Maturing was related with an anorexia, and voraciously consuming food)
expansion in the quantity of standard and deficient weight control plans with a lot
menstrual cycles, a diminishing in serum of hyper caloric and industrialized
androgen levels, and decrease in IR(18). nourishments are common in adolescence.
The explanations behind this attenuation of Dietary direction, incitement to physical
PCOS highlights after some time are not action, and self-care ought to be a piece of
satisfactory. Different examinations have the indispensable consideration for
concentrated on PCOS appearances in adolescence girls.
specific age gatherings, as detailed below. PCOS in postmenopausal women
PCOS in childhood: The endure with hyperandrogenism much after
communication between a genetic menopausal progress and keep on showing
inclination and some pre-birth and postnatal metabolic adjustments and MS with
ecological variables appears to partake in expanded danger of cardiovascular sickness.
the pathophysiology of PCOS. Intrauterine Consequently, postmenopausal women with
development hindrance or little for a past history with PCOS during the
gestational age (or both) and elevated levels conceptive years may in any case have
of androgens during the intrauterine period indications of the syndrome (9, 38).
could prompt an expanded creation of Researchers have examined other
glucocorticoids which may initiate therapeutic measures, for example,
epigenetic alterations and increment the foundational microorganism treatment, for
hazard of PCOS (35). infertility. Stem cells are undifferentiated
cells with the capacity to restore themselves
International Journal of Science and Healthcare Research (www.ijshr.com) 205
Vol.5; Issue: 3; July-September 2020Maged MN et.al. Polycystic ovary syndrome (PCOS): current and future therapy
for extensive stretches without critical wanted, and improving general prosperity
changes in their general properties. They and personal satisfaction.
can separate into different particular cell
types under certain physiological or 1. Metabolism
experimental conditions. Because of the The first line of treatment in quite a
restrictions of utilizing embryological and while with PCOS ought to be the
induced pluripotent stem cells, there is improvement in way of life. In overweight
incredible enthusiasm for mesenchymal and obese, weight reduction because of
stem cells (MSCs), which are free from both changes in diet and physical movement
moral concerns and teratoma formation diminishes serum insulin and androgen
(39). levels and decreases the risk of creating
MSCs, additionally called glucose intolerance and type 2 diabetes.
mesenchymal stromal cells, are a subset of Pharmacological mediations are shown
non hematopoietic adult stem cells that within the sight of IR/glucose narrow
begin from the mesoderm. They have self- mindedness or dyslipidemia that continue
renewal capacities and multilineage after way of life modifications (39).
separation into not just mesoderm Metformin is the most generally
heredities, for example, chondrocytes, utilized medication for the metabolic control
osteocytes, and adipocytes, yet additionally of these patients (49). The restorative
ectodermic and endodermic cells (40-42). impacts of metformin as insulin-sharpening
MSCs can be gathered from a few grown-up and hypoglycemic agent have been very
tissues, for example, bone marrow, well confirmed in l women with PCOS (50).
menstrual blood, fat tissue, the umbilical Be that as it may, in spite of what is usually
string, and placenta (43-47). accepted or what observational uncontrolled
examinations suggest (49), there is no
DISCUSSION persuading proof that metformin lessens
Treatment of PCOS ought to be BMI in women with PCOS compared and
proposed not exclusively to lighten placebo (50). The expansion of metformin
indications yet additionally to forestall the may have negligible advantage on the BMI
event of long term complications. Joined of women who get antiandrogen and joined
oral contraceptives and anti androgens is the oral contraceptive (39). Metformin doesn't
standard consideration to decrease androgen appear to diminish body adiposity as it has
levels and treat symptoms while giving nearly nothing if any impact on decreasing
endometrial protection (48). waist circumference and serum triglyceride
Notwithstanding, the therapeutic levels in women with PCOS (50).
arrangement ought to be custom-made Current examinations are
relying upon the longing (or not) of the investigating the theory that genomic
patient to get pregnant, requirement for variations characterize the responsiveness to
tasteful methodology, and the nearness of metformin treatment among women with
associative metabolic adjustments. PCOS (51). Since Metformin frequently has
The general objectives of treatment gastrointestinal symptoms, new
of women with PCOS incorporate the pharmaceutical arrangements particularly
moderation of hyper androgenic intended for vaginal delivery are a work in
manifestations, the executives of metabolic progress thus far has been powerful in a
variations from the norm and decrease of preclinical model of PCOS (52).
hazard factors for type 2 diabetes and Liraglutide is a glucagon-like
cardiovascular ailment, counteraction of peptide receptor 1 agonist endorsed for
endometrial hyperplasia, arranging and rewarding kind 2 diabetes and stoutness. In
acquiring a safe pregnancy whenever obese women with PCOS, liraglutide was
viable to actuate critical weight reduction
International Journal of Science and Healthcare Research (www.ijshr.com) 206
Vol.5; Issue: 3; July-September 2020Maged MN et.al. Polycystic ovary syndrome (PCOS): current and future therapy
and decrease waist f circumference (53). 2. Quality of life
Orlistat is a lipase inhibitor named for PCOS shows in women at
treatment of weight loss. In overweight or reproductive age when issues, for example,
corpulent women with PCOS, Orlistat is finding an accomplice, and framing a family
powerful to initiate weight reduction and are frequently pertinent. Variables that
improve clinical and biochemical markers contrarily affect personal satisfaction
of hyperandrogenism and IR (54). Elements that adversely influence physical
Myo-and D-chiro-inositol are appearance or womanliness or bargain
insulin-sensitizing agents that go about as ripeness are wellsprings of incredible
second flag-bearers in insulin flagging. uneasiness (63).
These mixes have been assessed as potential The psychological effect of PCOS
options in compared to metformin in PCOS may even outperform that of chronic
women with IR. Inositol isoforms mediate diseases, for example, asthma, diabetes,
insulin action in many target organs, joint inflammation, and coronary heart
including the ovary (55). In a mouse model disease (64).
of PCOM actuated by steady light Depression and anxiety are
introduction, the theca/ granulosa cell layer exceptionally common in women with
thickness proportion and the opportunity to PCOS, with a fourfold increment in the
pregnancy were decreased by treatment with depression symptoms side effects in patients
myo-inositol and D-chiro-inositol in a 40:1 with the condition when compared with
molar ratio (56). controls, even after change the BMI (65).
Prior clinical investigations without Day by day weakness and rest issues,
a placebo treatment or metformin changes in hunger, and loss of enthusiasm
demonstrated an a decrease in serum for regular exercises were the most widely
testosterone alongside an increase in SHBG recognized symptoms (66). Accordingly, the
levels following 6month of treatment with assessment of personal satisfaction in
myo-inositol alone or related with D-chiro- women with PCOS is fundamental for better
inositol (57) and no distinction between D- care and clinical management of these
chiro-inositol alone or joined with myo- patients.
inositol on the quantity of develop oocytes
recovered for in vitro preparation (IVF)(58). 3. Infertility
A late meta-examination presumed that In overweight or obese patients with
myo-inositol supplementation for IVF didn't PCOS who wish to conceive, life style
improve oocyte or embryo quality(59). changes focused on weight reduction ought
Given the current body of evidence, to be the achievement of previously
we accept that inositol treatment may turn established inclination directing. Loss of 5
into an option for metabolic improvement of to 7% of body weight might be successful to
PCOS women who don't endure metformin, advance menstrual cycle regularization and
yet information with a vis-à-vis correlation spontaneous ovulation (39). On the off
among inositols and metformin are as yet chance that the woman can't get thinner or
absent. Three little, single-focus randomized doesn't re-establish ovulatory cycles,
controlled examinations distributed in 2017 treatment ought to be individualized while
tended to this inquiry and discovered better considering duration of infertility, the
outcomes with either myo-inositol (60) or woman's age, and the risks of pregnancy at
metformin (61) or comparative advantages that age, and the factors that might be
with the two drugs (62). As indicated by the related to her difficulty to lose weight.
Inter-national PCOS Network, inositol (in Preconception care incorporates folic acid
any structure) ought to be viewed as an supplementation at a dose of 0.4 mg/day and
experimental treatment in PCOS (9). cessation of smoking and alcohol
consumption.
International Journal of Science and Healthcare Research (www.ijshr.com) 207
Vol.5; Issue: 3; July-September 2020Maged MN et.al. Polycystic ovary syndrome (PCOS): current and future therapy
The second line of treatment (after particularly in obese patients, which
life style interventions) is ovulation translates into higher pregnancy and live
induction. This progression must be gone birth rates (68, 72). Fundamental
with careful evaluation of different reasons information additionally proposes that
for infertility, for example, male factor or letrozole is better than metformin in
tubal obstruction, which request IVF and addition to CC to induce ovulation as
may exist together with PCOS. evaluated by the clinical pregnancy rate in
Clomiphene citrate (CC) is the randomized clinical trial (73).
reference therapy for ovulation induction in If there is failure of oral ovulation
an ovulatory woman with PCOS. Without inducers, injectable gonadotropins
ovulation for three cycles of CC at the combined with coordinated intercourse,
highest dose (150 mg/day), the woman can intrauterine insemination, or IVF might be
be considered non-responsive and another utilized. The addition of metformin to
medication ought to be presented as an gonadotropins has given some advantage in
adjuvant or substitute for CC. low-complexity treatment (coordinated
Compared and placebo treatment, intercourse or intrauterine insemination)
metformin lessens serum testosterone levels however not in IVF (70, 74). Fundamental
and increases the frequency of spontaneous outcomes propose that liraglutide at low
ovulation and regular menstrual cycles in dose can assist with improving the result of
patients with PCOS (51). Be that as it may, IVF treatment in obese women with PCOS
in light of the fact that it accomplishes lower (75).
live birth rates compared with CC, Women with PCOS should be
metformin is no longer prescribed to induce advice about the most fortunate second for
ovulation (50, 67). pregnancy, considering the obstetric,
Besides, there is no conclusive proof metabolic, and cardiovascular risks that
about whether the relationship of metformin might be available. Along these lines, safe
with CC varies from CC alone in live birth contraception is a piece of the essential
rates. the addition of metformin to CC care(76)as it permits delaying pregnancy
increases the ovulation and clinical while implementing life style interventions
pregnancy rates but also, the miscarriage to lose fat mass and improve the metabolic
rate compared to CC alone(50,68). In homeostasis so as to get a pregnancy as well
women resistant to CC, limited proof as a fruitful full-term pregnancy with both
recommends that adding metformin may mother and baby healthy.
increase the pregnancy rate (67).
Maintaining metformin during gestation Future Perspectives
doesn't appear to prevent unfavorable MSCs have exhibited incredible
outcomes (50, 67, 69, and 70) potential and accessibility for rewarding
Also, may in fact increase the risk of future female infertility in animal and human
overweight in offspring (71). studies. Autologous adipose derived stem
The aromatase inhibitor letrozole at cells are particularly helpful on the grounds
a dose of 2.5 mg/day might be utilized as a that they are effectively acquired, and avoid
choice to induce ovulation in patients who graft rejection after transplantation. In
have failed to respond to CC. numerous ongoing decades, autologous adipose
examinations recommend that letrozole can derived stem cells transplantation or
be utilized as first-line treatment in infusion have demonstrated constructive
ovulation induction however this utilization outcomes on rodent models can expand
stays off-name. The dose might be increased treatment rates. Be that as it may, there are a
by 2.5 mg/day to a limit of 7.5 mg/day. The few primary bearings for utilizing MSC to
major advantage of letrozole over CC is treat infertile women caused by ovarian or
better ovulation-induction response, uterine factors: (1) Most examinations have
International Journal of Science and Healthcare Research (www.ijshr.com) 208
Vol.5; Issue: 3; July-September 2020Maged MN et.al. Polycystic ovary syndrome (PCOS): current and future therapy
been done on little animals, and there is a confirm the therapeutic effect of MSCs in
genuine absence of significant exploration fertility medicine. (2) The mechanism of
in large animals models that all the more MSCs in treating dysfunction of female
intently emulate the ovarian or endometrial reproductive organs is still unknown.
pathophysiology of human female Possibilities include promoting
infertility. Moreover, randomized controlled angiogenesis, differentiating into functional
trials ought to be led to affirm the cells, and a paracrine mechanism. Among
therapeutic impact of MSCs in fertility these, a paracrine mechanism might be the
medication. (2) The mechanism of MSCs in most important for female infertility
treating dysfunction of female reproductive treatment. However, beneficial paracrine
organs is as yet obscure. Possibilities factors remain unknown and multiple
include promoting angiogenesis, mechanisms may be synergistic. (3) While
differentiating into functional cells, and a MSC therapy is promising, the limited
paracrine system. Among these, a paracrine survival and engraftment of bioactive agents
system may be the most significant for due to a hostile environment is a bottleneck
female infertility treatment. Be that as it for disease treatment.
may, useful paracrine factors stay obscure
and different systems might be synergistic. Conflict of interest
(3) While MSC treatment is promising, the All authors declare no conflicts of interest.
limited survival and engraftment of
bioactive operators because of a hostile Authors’ contribution
Authors have equally participated and shared
environment is a bottleneck for disease every item of the work.
treatment.
REFERENCES
CONCLUSION 1. Barry JA, Azizia MM, Hardiman PJ: Risk
New insights into the cross-talk of endometrial, ovarian and breast cancer in
between muscle, fat, brain, and ovary tissue women with polycystic ovary syndrome: a
support the concept that PCOS is a systemic systematic reviewandmeta-analysis. Hum
syndrome. The classic reproductive and Reprod Update. 2014; 20(5):748–58.
dermatological features of PCOS are just the 2. Çakıroğlu Y, Vural F, Vural B: The
visible part of a more complex mechanism. inflammatory markers in polycystic ovary
The inflammatory and metabolic syndrome: association with obesity and IVF
outcomes. J EndocrinolInvest. 2016; 39(8):
derangements associated with PCOS are 899–907.
explained in part by the coexistence of IR 3. de Leo V, Musacchio MC, Cappelli V, et
and obesity but are further fuelled by the al.: Genetic, hormonal andmetabolic aspects
androgen excess. The therapeutic plan of PCOS: an update. ReprodBiolEndocrinol.
should be tailored to the patient phenotype, 2016; 14(1): 38.
complaints, and reproductive desire. 4. Durmus U, Duran C, Ecirli S: Visceral
Medical treatments have not seen any adiposity index levels in overweight and/or
breakthrough in recent years. Of note, the obese, and non-obese patients with
aromatase inhibitor letrozole seems to be polycystic ovary syndrome and its
more effective than the reference drug CC to relationship with metabolic and
treat infertility due to PCOS. Integral inflammatory parameters. J Endocrinol
Invest. 2017; 40(5): 487–97.
management by a multidisciplinary team 5. McCartney CR, Marshall JC: Clinical
may help patients to adhere to lifestyle Practice. Polycystic Ovary Syndrome. N
interventions and thereby reduce body Engl J Med. 2016; 375(1): 54–64.
adiposity and recover their metabolic and 6. Spritzer PM, Lecke SB, Satler F, et al.:
reproductive health. Adipose tissue dysfunction, adipokines, and
Furthermore, a randomized low-grade chronic inflammation in
controlled trial should be conducted to
International Journal of Science and Healthcare Research (www.ijshr.com) 209
Vol.5; Issue: 3; July-September 2020Maged MN et.al. Polycystic ovary syndrome (PCOS): current and future therapy
polycystic ovary syndrome. Reproduction. 17. Katulski K, Podfigurna A, Czyzyk A, et al.:
2015; 149(5):R219–R227. Kisspeptin and LH pulsatile temporal
7. Rotterdam ESHRE/ASRM-Sponsored coupling in PCOS patients. Endocrine.
PCOS Consensus Workshop Group: 2018; 61(1):149–57.
Revised 2003 consensus on diagnostic 18. Brown ZA, Louwers YV, Fong SL, et al.:
criteria and long-term health risks related to The phenotype of polycystic ovary
polycystic ovary syndrome. FertilSteril. syndrome ameliorates with aging.
2004; 81(1):19–25. FertilSteril. 2011; 96(5): 1259–65.
8. Wang R, Mol BW: The Rotterdam criteria 19. Mishra A, Younossi ZM: Epidemiology and
for polycystic ovary syndrome: evidence- Natural History of Non-alcoholic Fatty
based criteria? Hum Reprod. 2017; 32(2): Liver Disease. J ClinExpHepatol. 2012;
261–4. 2(2):135–44.
9. Teede HJ, Misso ML, Costello MF, et al.: 20. Rocha ALL, Faria LC, Guimarães TCM, et
Recommendations from the international al.: Non-alcoholic fatty liver disease in
evidence-based guideline for the assessment womenwithpolycysticovarysyndrome:syste
and management of polycystic ovary maticreviewandmeta-analysis. J Endocrinol
syndrome. Hum Reprod. 2018; 33(9):1602– Invest. 2017; 40(12):1279–88.
18. 21. Boström P, Wu J, Jedrychowski MP, et al.:
10. Day F, Karaderi T, Jones MR, et al.: Large- A PGC1--dependent myokine that drives
scale genome-wide meta-analysis of brown-fat-like development of white fat and
polycystic ovary syndrome suggests shared thermogenesis. Nature. 2012; 481(7382):
genetic architecture for different diagnosis 463–8
criteria. PLoS Genet. 2018; 22. Polyzos SA, Anastasilakis AD, Efstathiadou
14(12):e1007813. ZA, et al.: Irisin in metabolic diseases.
11. Daan NM, Jaspers L, Koster MP, et al.: Endocrine. 2018; 59(2):260–74.
Androgen levels in women with various 23. Colaianni G, Cuscito C, Mongelli T, et al.:
forms of ovarian dysfunction: associations The myokineirisinincreases cortical bone
with cardiometabolic features. HumReprod. mass. ProcNatlAcadSci U S A. 2015;
2015; 30(10): 2376–86. 112(39):12157–62.
12. Dumesic DA, Oberfield SE, Stener-Victorin 24. Uysal N, Yuksel O, Kizildag S, et al.:
E, et al.: Scientific Statement on the Regular aerobic exercise correlates with
DiagnosticCriteria,Epidemiology,Pathophys reduced anxiety and increased levels of
iology,andMolecularGeneticsof Polycystic irisin in brain and white adipose tissue.
Ovary Syndrome. EndocrRev. 2015; NeurosciLett. 2018; 676: 92–7.
36(5):487–525. 25. Lourenco MV, Frozza RL, de Freitas GB, et
13. Legro RS, Arslanian SA, Ehrmann DA, et al.: Exercise-linked FNDC5/irisin rescues
al.: Diagnosis and treatment of synaptic plasticity and memory defects in
polycysticovary syndrome: an Endocrine Alzheimer’s models. Nat Med. 2019; 25(1):
Society clinical practice guideline. J Clin 165–75.
EndocrinolMetab. 2013; 98(12):4565–92. 26. Moreno-Navarrete JM, Ortega F, Serrano
14. Wierman ME, Arlt W, Basson R, et al.: M, et al.: Irisin is expressed and produced
Androgen therapy in women: a reappraisal: by human muscle and adipose tissue in
an Endocrine Society clinical practice association with obesity and insulin
guideline. J ClinEndocrinolMetab. 2014; resistance. J ClinEndocrinol
99(10):3489–510. 27. Zhang L, Fang X, Li L, et al.: The
15. Mario FM, Graff SK, Spritzer PM: Habitual association between circulating irisin levels
physical activity is associated with and different phenotypes of polycystic
improved anthropometric and androgenic ovary syndrome. J Endocrinol Invest. 2018;
profile in PCOS: a cross- sectional study. J 41(12): 1401–7.
Endocrinol Invest. 2017; 40(4):377–84. 28. Cai X, Qiu S, Li L, et al.: Circulating irisin
16. Cimino I, Casoni F, Liu X, et al.: Novel role in patients with polycystic ovary syndrome:
for anti-Müllerian hormone in the regulation a meta-analysis. Reprod Biomed Online.
of GnRH neuron excitability and hormone 2018; 36(2): 172–80.
secretion. Nat Commun. 2016; 7: 10055. 29. He C, Lin Z, Robb SW, et al.: Serum
Vitamin D Levels and Polycystic Ovary
International Journal of Science and Healthcare Research (www.ijshr.com) 210
Vol.5; Issue: 3; July-September 2020Maged MN et.al. Polycystic ovary syndrome (PCOS): current and future therapy
syndrome: A Systematic Review and Meta- contraceptives and/or antiandrogens versus
Analysis. Nutrients. 2015; 7(6): 4555–77. insulin sensitizers for polycystic ovary
30. Foroozanfard F, Jamilian M, Bahmani F, et syndrome: a systematic review and meta-
al.: Calcium plus vitamin D analysis. Hum Reprod Update. 2018; 24:
supplementation influences biomarkers of 225–41.
inflammation and oxidative stress in 41. Dominici M., Le Blanc K., Mueller I., et al.
overweight and vitamin D-deficient women Minimal criteria for defining multipotent
with polycystic ovary syndrome: A mesenchymal stromal cells. The
randomized double-blind placebo-controlled International Society for Cellular Therapy
clinical trial. ClinEndocrinol (Oxf). 2015; position
83(6): 888–94. statement. Cytotherapy. 2006;8(4):315–317
31. Irani M, Seifer DB, Grazi RV, et al.: 42. Dezawa M., Ishikawa H., Itokazu Y., et al.
Vitamin D Supplementation Decreases Bone marrow stromal cells generate muscle
TGF- β1 Bioavailability in PCOS: A cells and repair muscle degeneration.
Randomized Placebo-Controlled Trial. J Science. 2005;309(5732):314–317
ClinEndocrinolMetab. 2015; 100(11):4307– 43. Salem H. K., Thiemermann C.
14. Mesenchymal stromal cells: current
32. MartinsWP,KollmannM,Raine-FenningN: understanding and clinical status. Stem
Countingovarianfollicles:updated threshold Cells. 2010;28(3):585–596
for diagnosis of hyperandrogenic 44. Körbling M., Anderlini P. Peripheral blood
anovulation. Ultrasound Obstet Gynecol. stem cell versus bone marrow
2014; 44(2): 131–4. allotransplantation: does the source of
33. Dewailly D, Lujan ME, Carmina E, et al.: hematopoietic stem cells matter?
Definition and significance of polycystic Blood. 2001;98(10):2900–2908
ovarian morphology: a task force report 45. Meng X., Ichim T. E., Zhong J., et al.
from the Androgen Excess and Polycystic Endometrial regenerative cells: a novel stem
Ovary Syndrome Society. Hum Reprod cell population. Journal of Translational
Update. 2014; 20(3): 334–52. Medicine. 2007;5(1):1–10.
34. Fraissinet A, Robin G, Pigny P, et al.: Use 46. Barry F. P., Murphy J. M. Mesenchymal
of the serum anti-Müllerian hormone assay stem cells: clinical applications and
as a surrogate for polycystic ovarian biological characterization. The
morphology: impact on diagnosis and International Journal of Biochemistry &
phenotypic classification of polycystic Cell Biology. 2004;36(4):568–584
ovary syndrome. Hum Reprod. 2017; 32(8): 47. Lee O. K., Kuo T. K., Chen W.-M., Lee K.-
1716–22. D., Hsieh S.-L., Chen T.-H. Isolation of
35. Bellver J, Rodríguez-Tabernero L, Robles multipotentmesenchymal stem cells from
A, et al.: Polycystic ovary syndrome umbilical cord
throughout a woman’s life. J Assist Reprod blood. Blood. 2004;103(5):1669–1675.
Genet. 2018; 35(1): 25–39. | 48. in’t Anker P. S., Scherjon S. A., der Keur C.
36. Witchel SF, Oberfield S, Rosenfield RL, et K.-v., et al. Isolation of mesenchymal stem
al.: The Diagnosis of Polycystic Ovary cells of fetal or maternal origin from human
Syndrome during Adolescence. Horm Res placenta. Stem Cells. 2004;22(7):1338–1345
Paediatr. 2015; 83: 376–389. 49. Balen AH, Morley LC, Misso M, et al.: The
37. Fitzgerald S, DiVasta A, Gooding H: An management of anovulatory infertility in
update on PCOS in adolescents. women with polycystic ovary syndrome: an
CurrOpinPediatr. 2018; 30(4):459–465. analysis of the evidence to support the
38. Shah D, Bansal S: Polycystic ovaries - development of global WHO guidance.
beyond menopause. Climacteric.2014;17(2): Hum Reprod Update. 2016; 22(6): 687–708.
109–15. 50. Yang PK, Hsu CY, Chen MJ, et al.: The
39. Blum B., Benvenisty N. The tumorigenicity Efficacy of 24-Month Metformin for
of human embryonic stem cells. Advances Improving Menses, Hormones, and
in Cancer Research. 2008;100(8):133–158. Metabolic Profiles in Polycystic Ovary
doi: 10.1016/S0065-230X(08)00005-5. Syndrome. J ClinEndocrinolMetab. 2018;
40. Luque-Ramírez M, Nattero-Chávez L, Ortiz 103(3):890–9.
Flores AE, et al.: Combined oral
International Journal of Science and Healthcare Research (www.ijshr.com) 211
Vol.5; Issue: 3; July-September 2020Maged MN et.al. Polycystic ovary syndrome (PCOS): current and future therapy
51. Morley LC, Tang T, Yasmin E, et al.: 60. Mendoza N, Pérez L, Simoncini T, et al.:
Insulin-sensitising drugs (metformin, Inositol supplementation in women
rosiglitazone, pioglitazone, D-chiro-inositol) withpolycysticovarysyndromeundergoingint
for women with polycystic ovary syndrome, racytoplasmicsperminjection: a systematic
oligomenorrhea and subfertility. Cochrane review and meta-analysis of randomized
Database SystRev2017; 11: CD003053. controlled trials. Reprod Biomed Online.
52. Pedersen AJT, Stage TB, Glintborg D, et 2017; 35(5):529–35.
al.: The Pharmacogenetics of Metformin in 61. Jamilian M, Farhat P, Foroozanfard F, et al.:
Women with Polycystic Ovary Syndrome: Comparison of myo-inositol and metformin
A Randomized Trial. Basic Clin Pharmacol on clinical, metabolic and genetic
Toxicol. 2018; 122(2):239– parameters in polycystic ovary syndrome: A
53. Saini N, Sodhi RK, Bajaj L, et al.: randomized controlled clinical trial.
Intravaginal administration of metformin ClinEndocrinol (Oxf). 2017; 87(2): 194–
hydrochloride loaded cationic niosomes 200.
amalgamated with thermosensitive gel for 62. Tagliaferri V, Romualdi D, Immediata V, et
the treatment of polycystic ovary syndrome: al.: Metformin vsmyoinositol: which is
In vitro and in vivo studies. Colloids Surf B better in obese polycystic ovary syndrome
Biointerfaces. 2016; 144:161–9. patients? A randomized controlled crossover
54. Jensterle M, Kravos NA, Pfeifer M, et al.: A study. ClinEndocrinol (Oxf). 2017; 86(5):
12-week treatment with the long- acting 725–30.
glucagon-like peptide 1 receptor agonist 63. Fruzzetti F, Perini D, Russo M, et al.:
liraglutide leads to significant weight loss in Comparison of two insulin sensitizers,
a subset of obese women with newly metformin and myo-inositol, in women with
diagnosed polycystic ovary syndrome. polycystic ovary syndrome (PCOS).
HHormones (Athens). 2015; 14(1):81–90. GynecolEndocrinol. 2016; 33(1): 39–42.
55. Graff SK, Mario FM, Ziegelmann P, et al.: 64. Eggers S, Kirchengast S: The polycystic
Effects of orlistat vs. metformin on weight ovary syndrome--a medical condition but
loss-related clinical variables in women also an important psychosocial problem.
with PCOS: systematic review and meta- CollAntropol. 2001; 25(2): 673–85. PubMed
analysis. Int J ClinPract. 2016; 70(6):450– Abstract
61. 65. Coffey S, Bano G, Mason HD: Health-
56. Monastra G, Unfer V, Harrath AH, et al.: related quality of life in women with
Combining treatment with myo-inositol and polycystic ovary syndrome: a comparison
D-chiro-inositol (40:1) is effective in with the general population using the
restoring ovary function and metabolic Polycystic Ovary Syndrome Questionnaire
balance in PCOS patients. (PCOSQ) and the Short Form- 36 (SF-36).
57. Bevilacqua A, Dragotto J, Giuliani A, et al.: GynecolEndocrinol. 2006; 22(2): 80–6.
Myo-inositol andD-chiro-inositol (40:1) 66. Dokras A, Clifton S, Futterweit W, et al.:
reverse histological and functional features Increased risk for abnormal depression
of polycystic ovary syndrome in a mouse scores in women with polycystic ovary
model. J Cell Physiol. 2019; 234(6): 9387– syndrome: a systematic review and meta-
9398. analysis. Obstet Gynecol. 2011; 117(1):145–
58. Nordio M, Proietti E: The combined therapy 52.
with myo-inositol and D-chiro- inositol 67. Dokras A: Mood and anxiety disorders in
reduces the risk of metabolic disease in women with PCOS. Steroids.2012;77(4):
PCOS overweight patients compared to 338–41.
myo-inositol supplementation alone. Eur 68. Practice Committee of the American
Rev Med PharmacolSci. 2012; 16(5): 575– Society for Reproductive Medicine: Role of
81. metformin for ovulation induction in
59. Colazingari S, Treglia M, Najjar R, et al.: infertile patients with polycystic ovary
The combined therapy myo-inositol plus D- syndrome (PCOS): a guideline. FertilSteril.
chiro-inositol, rather than D-chiro-inositol, 2017; 108(3):426–41.
is able to improve IVF outcomes: results 69. Wang R, Kim BV, van Wely M, et al.:
from a randomized controlled trial. Arch Treatment strategies for women with WHO
Gynecol Obstet. 2013; 288(6): 1405–11. group II anovulation: systematic review and
International Journal of Science and Healthcare Research (www.ijshr.com) 212
Vol.5; Issue: 3; July-September 2020Maged MN et.al. Polycystic ovary syndrome (PCOS): current and future therapy
network meta-analysis. BMJ. 2017; 356: 74. Rezk M, Shaheen AE, Saif El-Nasr I:
j138. Clomiphene citrate combined with
70. Legro RS: Ovulation induction in polycystic metforminversusletrozoleforinductionofovul
ovary syndrome: Currentoptions. BestPract ationinclomiphene-resistant polycystic
Res ClinObstetGynaecol. 2016; 37: 152–9. ovary syndrome: a randomized clinical trial.
71. Bordewijk EM, Nahuis M, Costello MF, et GynecolEndocrinol. 2018; 34(4): 298–300.
al.: Metformin during ovulation induction 75. Kalem MN, Kalem Z, Gurgan T: Effect of
with gonadotrophins followed by timed metformin and oral contraceptives on
intercourse or intrauterine insemination for polycystic ovary syndrome and IVF cycles.
subfertility associated with polycystic ovary J Endocrinol Invest. 2017; 40(7): 745–52.
syndrome. Cochrane Database SystRev. 76. Salamun V, Jensterle M, Janez A, et al.:
2017; 1:CD009090. Liraglutide increases IVF pregnancy rates in
72. Hanem LGE, Stridsklev S, Júlíusson PB, et obese PCOS women with poor response to
al.: Metformin Use in PCOS Pregnancies first-line reproductive treatments: a pilot
Increases the Risk of Offspring Overweight randomized study. Eur J Endocrinol. 2018;
at 4 Years of Age: Follow-Up of Two RCTs. 179(1): 1–11.
J ClinEndocrinolMetab. 2018; 103(4):
1612–21. How to cite this article: Maged MN, Mohamed
73. Franik S, Eltrop SM, Kremer JA, et al.: MN, Shehata LH. Polycystic ovary syndrome
Aromatase inhibitors (letrozole) for (PCOS): current and future therapy.
subfertile women with polycystic ovary International Journal of Science & Healthcare
syndrome. Cochrane Database SystRev. Research. 2020; 5(3): 202-213.
2018; 5:CD010287.
******
International Journal of Science and Healthcare Research (www.ijshr.com) 213
Vol.5; Issue: 3; July-September 2020You can also read
