[Downloaded free from http://www.jpbsonline.org on Sunday, November 7, 2021, IP: 182.253.163.

99]

Original Article

Polycystic Ovarian Syndrome–Related Depression in Adolescent

Girls: A Review
Saleha Sadeeqa, Tehreem Mustafa, Sumaira Latif

Institute of Pharmacy, Polycystic ovarian syndrome (PCOS), a common endocrinal disorder of

Abstract
Lahore College for Women
reproductive age characterized by heterogeneous complications, is nowadays
University, Lahore,
Pakistan
prevailing among females at adolescent stage. Infrequent or prolonged menstrual
periods, excess hair growth, acne, and obesity can occur in women with PCOS.
In adolescents, infrequent or absence of menstruation may raise chances for
this condition. The increased prevalence of PCOS among general population
throughout the world is found to be 5%–10% in the women of reproductive age,
and about 40% women with PCOS experience depression, particularly young
girls. The exact cause of PCOS is unknown. Early diagnosis and treatment along
with weight loss may reduce the risk of long-term complications. Depression and
anxiety are common in women with PCOS but are often overlooked and therefore
left untreated. Along with the physical disturbances, many mental problems are
also associated with PCOS. Therefore, PCOS not only has problems associated
with reproduction but also has associated crucial metabolic and psychological
health risks with increasing age of the patients. Because of the increased number
of cases with PCOS around the world in present times, with prominent symptom
of, specifically, depression at the adolescent stage, it is important to highlight the
disease.
Keywords: Adolescent, Depression, Polycystic Ovarian Syndrome

Introduction various investigators,[4,5] particularly due to obesity,

P  olycystic ovarian syndrome (PCOS) is the most
common endocrine disorder in women, having
15%–20% prevalence among infertile women.[1] It occurs
in 6%–10% of women of reproductive age with a higher
prevalence in obese women.[2] It is a genetic condition
that is complex with multiple phenotypes and various
appearances. The highly occurring heterogeneous
syndrome can be characterized by polycystic ovaries
(PCO), ovulatory dysfunction, and clinical and/or
biochemical androgen excess. Patients with PCOS are
more prone to serious health troubles, particularly
reproductive dysfunctions. Metabolic disturbances
are prevalent in two-thirds of women with PCOS,
which may lead to the high risk of cardiovascular
and type-2 diabetes mellitus in them.[3] Psychosocial
problems arise in patients with PCOS, as shown by
excessive body hairs, infertility, and changes in the
physical appearances. As a whole, different reasons for
psychological stress, particularly among the adolescent
girls associated with PCOS, is discussed in this article
with probable management and treatment overview to
cope with the PCOS stress for young girls.
Materials and Methods
A literature research was performed on Google Scholar
and Medline databases. Various studies on metformin
were analyzed. The search terms used were Polycystic
ovarian syndrome, Depression, and Adolescent.
Address for correspondence: Dr. Saleha Sadeeqa,
Institute of Pharmacy, Lahore College for Women University,
Lahore, Pakistan.
E-mail: salehasadeeqa@gmail.com

This is an open access journal, and articles are distributed under the terms of the
Access this article online
Creative Commons Attribution-NonCommercial-ShareAlike 4.0 License, which allows
Quick Response Code: others to remix, tweak, and build upon the work non-commercially, as long as
Website: www.jpbsonline.org ­appropriate credit is given and the new creations are licensed under the identical terms.

For reprints contact: reprints@medknow.com

How to cite this article: Sadeeqa S, Mustafa T, Latif S. Polycystic ovarian

DOI: 10.4103/jpbs.JPBS_1_18
syndrome–related depression in adolescent girls: A review. J Pharm
Bioall Sci 2018;10:55-9.

© 2018 Journal of Pharmacy and Bioallied Sciences  |  Published by Wolters Kluwer - Medknow 55
[Downloaded free from http://www.jpbsonline.org on Sunday, November 7, 2021, IP: 182.253.163.99]
Sadeeqa, et al.: PCOS-related depression
Results
Prevalence
Studies reviel the increased prevalence of PCOS among
the general population throughout the world, which
ranges from 5% to 10%[6] in women of reproductive
age, and about 40% women with PCOS experience
depression,[7] particularly the young girls. The rate of
PCOS in South-Western United States was found to be
4%. The incidence screened out to be 9.13% in Indian
adolescents.[8] As per the National Institute of Health,
the rate of PCOS increases from 6.5% to 6.8% in adult
reproductive-aged woman worldwide.[9]
Pathophysiology of the disease
The pathophysiology of PCOS is contributed by both
the genetic and the environmental factors.[10] Genetically,
it can be explained as an increase in the levels of ovarian
hyperandrogenism[11] due to the influence of luteinizing
hormone (LH) and insulin. Elevated LH level that
ultimately causes an increase in the production of
androgens from cells, called theca cells in young girls
and women having PCOS, may provide an insight of
aberrant secretion levels of Gonadotropin-Releasing
Hormone.[12] The environmental factors primarily
include obesity, nutrition or eating disorders,[13] and
insulin resistance.[14]
Moreover, the pathophysiology of depression and
mental stress during PCOS is linked to various changes
that include psychological changes such as high activity
of pro-inflammatory markers and immune system
during stress.[15]
Signs and symptoms
Patients with PCOS usually express symptoms from
puberty.[10] It may include transient postmenarcheal
anovulation and multicystic ovaries. The general
three criteria featuring PCOS established by PCOS
consensus were; clinical hyperandrogenism, oligo/
amenorrhea, and PCO identified in ultrasonography,
which are the definitions, not sufficient to diagnose
PCOS in adolescents, where PCOS even if present can
be identified till adulthood. Oligomenorrhea exists if
menstrual cycle lasts for above 35  days whereas acne,
androgenic alopecia, or hirsutism are the clinical
symptoms of hyperandrogenism.[16-18]
The etiology of PCOS can be contributed to both
genetic predisposition and lifetime factors.[19] The
mechanism of genetic disposition in the development
of PCOS is well established, but environmental factors
may include sedentary lifestyle, imbalanced diet that
may result in insulin resistance, and obesity, which
are potential factors in the development of PCOS.[20]
56 Journal of Pharmacy and Bioallied Sciences  ¦  Volume 10  ¦  Issue 2  ¦  April-June 2018
Although women having PCOS have advanced chances
of developing depression than women who are not
affected by PCOS,[21] obesity aggravates the condition.
Obesity usually coexists with PCOS. The 40%–60% of
women who have PCOS are obese.[22] In patients with
PCOS, the major determinant of metabolic phenotype
is obesity, whereas teen juveniles are observed as
protected from the metabolic disturbances of PCOS.[23]
The clinical and biochemical phenotype of PCOS are
greatly influenced in the case of genetically predisposed
individuals.[24]
Diagnosis
The criteria for the diagnosis of PCOS in adults are also
applicable to the adolescents as the PCOS’s diagnosis
criteria in an adolescent are not defined yet.[21] Some
simple clinical tests can be performed to diagnose PCOS
as suggested by PCOS consensus workshop group. These
include; 1) the level of testosterone should be checked
in girls who showed symptoms of high androgen levels
2) the levels of Follicle-Stimulating Hormone (FSH),
LH, prolactin, and estradiol should be measured in the
case of oligo- or amenorrhea (anovulation); and 3) the
transabdominal scanning of ovaries by ultrasound
can prove helpful in an adolescent with menstrual
disturbances or hyperandrogenism. Routine 75 g oral
glucose tolerance test in an adolescent with body mass
index (BMI) of >30 kg·m−2 is advisable.
Mental stress among adolescent with PCOS
PCOS-related mental stress is well studied by Himelein
et al.,[25] which indicates the symptoms of PCOS mostly
affecting the patients include increased androgen levels,
menstrual disturbances, infertility,[5] obesity, hirsutism,
or alopecia, but nowadays behavioral scientists start
observing significant levels of mental stress in patients
with PCOS,[26] particularly among the young girls.
This may be because young girls are more concerned
about their physiology and physical health during
adolescence. One of the studies reveals clear stress
symptoms explicated in a group of women who are
having PCOS than the women who are not affected
by PCOS.[27] Depression and stress are the high-risk
factors among the patients with PCOS along with the
impaired metabolic and reproductive features. This
high level of depression and anxiety in the patients
with PCOS may be due to various reasons such as high
BMI and demoralization faced by patients with PCOS
in the society, which when severe may lead to social
withdrawal.[12] The clinical symptoms of PCOS, i.e.,
hyperandrogenism and infertility, add significantly to
the severity of the conditions.[28]
[Downloaded free from http://www.jpbsonline.org on Sunday, November 7, 2021, IP: 182.253.163.99]
Sadeeqa, et al.: PCOS-related depression
In addition, studies carried out by Hollinrake et al.[21]
determined some more reasons for increased risk of
depression among patients with PCOS than in control
group. Patients with family history of infertility and
depression along with high BMI factor and sleep
disturbances[29] and exhaustion followed by decreased
interest in daily chores and appetite changes are the
most common factors of depression among the patients
with PCOS.
Interesting findings were obtained when clinical/
biochemical parameters were correlated with stress
in young women with PCOS.[30] These studies
reveal significantly higher levels of hirsutism and
testosterone in the group of women with PCOS along
with the higher BMI, LH/FSH, and Waist-to-Hip
Ratio (WHR). Depression and emotional stress were
analyzed with Turkish version of the Beck Depression
Inventory and 12-item General Health Questionnaire.
Both parameters were found to be high in the patients
with PCOS than that of the control group, which when
correlated with the clinical/biochemical parameters
depict the positive relation between them. Among all
the factors in patients with PCOS, obesity is the most
prominent feature causing an elevation in emotional
stress level and depression among adolescent girls than
BMI, and WHR also causes a notable increase in the
levels of mental stress and depression. Factors such as
high sympathetic activity, elevated cortisol levels, and
low level of serotonin are associated with both, insulin
and depression.[19] It is reported that different factors
of PCOS to develop depression in a woman will lead
to induce higher insulin resistance and impaired fasting
glucose than undepressed PCOS women.[31] There are
several types of researches that reported a correlation
between levels of serum androgen and depression
scores.[32] It is observed that due to the appearance of
physical characteristics of hyperandrogenism, which
includes obesity, cystic acne, hirsutism, hair loss
(alopecia), and seborrhea, more negative self-image
with low self-esteem is induced, which cause high
depression levels and psychological distress among
women with PCOS.[19,23-34]
PCOS depression management and treatment in
adolescents
According to the recent management guidelines by
Consensus on treatment of PCOS, the counseling
related to the lifestyle changes, i.e., obesity control,
daily walk, prevent smoking and alcohol consumption,
clinical symptoms (menses irregularities) particularly in
young girls, insulin resistance before medical treatment
can produce positive outcomes[35] by lowering the stress
level in PCOS patients. Standard metformin treatment
Journal of Pharmacy and Bioallied Sciences  ¦  Volume 10  ¦  Issue 2  ¦  April-June 2018
in PCOS cases if practiced regularly for 6 months can
help to reduce various reproductive, physiological, and
psychological problems.[36]
Several stress management interventions are also
suggested to normalize Hypothalamic-Pituitary-Adrenal
(HPA) axis at a normal pace, which may act as stressors
by exaggerating Sympathetic Nervous System response
in women with PCOS.[37] It may include cognitive
behavioral therapy and relaxation at the stage when
standard metformin treatment fails to produce the
expected stress relief in patients with PCOS.[38]
The reason of distress along with the hirsutism among
adolescents with PCOS is mostly due to the excess levels
of androgens. Antiandrogen therapy can be carried out
(if necessary) along with the cosmetic management[39]
(provided that hair removal method is authorized).
The major challenge is the prevention of long-term
complications of PCOS. The strong control of diet
and an active lifestyle can effectively reduce the risk of
diabetes in at-risk adults.[40]
Discussion
Polycystic ovarian syndrome is a chronic, heterogeneous
disorder of endocrine system with prominent features
of androgens, menstrual disturbances, and depression.
It is a leading cause of pregnancy complications and
infertility among women and causes depression among
young girls. The reason for the extreme mental stress
and depression in an adolescent with PCOS is due to
the appearance of embarrassing symptoms such as
hirsutism, obesity, and acne during adolescence.[4]
Obesity was pointed to be the major factor causing
depression and emotional stress among adolescents
with PCOS,[22] which needs to be managed both
psychologically and clinically to overcome mental
stress in patients. Thus, it is concluded that major
psychological and behavioral intervention approaches
that are dominantly useful in relieving depression in
patients with PCOS particularly at the adolescent
stage are quality sleep, improved lifestyle (healthy
diet and preventing sedentary lifestyle), and regular
exercise. These psychosocial techniques prove useful in
reducing stress and depression through weight loss and
physiological maintenance.
It is now an established fact that maintenance of
healthy and active lifestyle can support to lessen both
the physiological and the psychological symptoms.[41]
So, it is recommended that stress in women having
PCOS is treated primarily psychosocially and clinically
in a later stage, which is also a more economical and
promising option.
57
[Downloaded free from http://www.jpbsonline.org on Sunday, November 7, 2021, IP: 182.253.163.99]
Sadeeqa, et al.: PCOS-related depression
Conclusions
PCOS is a chronic, heterogeneous disorder of endocrine
system with prominent features of androgens, menstrual
disturbances, and depression. Depression and stress are
the high-risk factors among the patients along with the
impaired metabolic and reproductive features. Obesity
was pointed to be the major factor causing depression
and emotional stress among adolescents.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
References
1. Farideh ZZ, Mina J, Mohammad MN, Nasrine A, Fedyeh
H. Psychological distress in women with polycystic ovary
syndrome from imam Khomeini hospital, Tehran. J Reprod
Infertil 2012;13:111-5.
2. Hamdi CE, Aysun B, Burçin N, Ayşin N, Cem Ç, Yasemin
Y, et  al. Anxiety and depression states of adolescents
with polycystic ovary syndrome. Turk J Med Sci 2017;47.
doi:10.3906/sag-1708-131.
3. Dennett CC, Simon J. The role of polycystic ovary syndrome
in reproductive and metabolic health: overview and approaches
for treatment. Diabetes Spectrv 2015;28:116-20.
4. McCook JG, Reame NE, Thatcher SS. Health-related quality
of life issues in women with polycystic ovary syndrome. J
Obstet Gynecol Neonatal Nurs 2005;34:12-20.
5. Trent ME, Austin B, Rich M, Gordon CM. Overweight status
of adolescent girls with polycystic ovary syndrome: body mass
index as mediator of quality of life. Ambu Pediat 2005;5:107-11.
6. Azziz R, Woods KS, Reyna R, Key TJ, Knochenhauer ES,
Yildiz BO. The prevalence and features of the polycystic ovary
syndrome in an unselected population. J Clin Endocrinol
Metab 2004;89:2745-9.
7. Kerchner A, Lester W, Stuart SP, Dokras A. Risk of
depression and other mental health disorders in women with
polycystic ovary syndrome:  a longitudinal study. Fertil Steril
2009;91:207-12.
8. Nidhi R, Padmalatha V, Nagarathna R, Amritanshu
R. Prevalence of polycystic ovarian syndrome in Indian
adolescents. J Pediatr Adolesc Gynecol 2011;24:223-7.
9. Asunción M, Calvo RM, San Millán JL, Sancho J, Avila S,
Escobar-Morreale HF. A prospective study of the prevalence of
the polycystic ovary syndrome in unselected Caucasian women
from Spain. J Clin Endocrinol Metab 2000;85:2434-8.
10. Diamanti-Kandarakis E, Piperi C, Spina J, Argyrakopoulou
G, Papanastasiou L, Bergiele A, et  al. Polycystic ovary
syndrome: the influence of environmental and genetic factors.
Hormones-Athens 2006;5:17.
11. Rosenfield RL, Ehrmann DA. The pathogenesis of polycystic
ovary syndrome (PCOS):  the hypothesis of PCOS as
functional ovarian hyperandrogenism revisited. Endocr Rev
2016;37:467-520.
12. Veldhuis JD, Pincus SM, Garcia-Rudaz MC, Ropelato MG,
Escobar ME, Barontini M. Disruption of the joint synchrony
of luteinizing hormone, testosterone, and androstenedione
secretion in adolescents with polycystic ovarian syndrome. J
Clin Endocrinol Metab 2001;86:72-9.
58 Journal of Pharmacy and Bioallied Sciences  ¦  Volume 10  ¦  Issue 2  ¦  April-June 2018
13. Månsson M, Holte J, Landin-Wilhelmsen K, Dahlgren E,
Johansson A, Landén M. Women with polycystic ovary
syndrome are often depressed or anxious—a case control study.
Psychoneuroendocrinology 2008;33:1132-8.
14. McCartney CR, Blank SK, Prendergast KA, Chhabra S, Eagleson
CA, Helm KD, et  al. Obesity and sex steroid changes across
puberty: evidence for marked hyperandrogenemia in pre- and early
pubertal obese girls. J Clin Endocrinol Metab 2007;92:430-6.
15. Diamanti-Kandarakis E, Christakou C, Palioura E, Kandaraki
E, Livadas S. Does polycystic ovary syndrome start in
childhood? Pediatr Endocrinol Rev 2008;5:904-11.
16. Diamanti-Kandarakis E. PCOS in adolescents. Best Pract Res
Clin Obstet Gynaecol 2010;24:173-83.
17. Cooney LG, Lee I, Sammel MD, Dokras A. High prevalence
of moderate and severe depressive and anxiety symptoms
in polycystic ovary syndrome:  a systematic review and
meta-analysis. Hum Reprod 2017;32:1075-91.
18. Cooney LG, Dokras A. Depression and anxiety in polycystic
ovary syndrome: etiology and treatment. Curr Psychiatry Rep
2017;19:83.
19. Ibáñez L, Díaz R, López-Bermejo A, Marcos MV. Clinical
spectrum of premature pubarche: links to metabolic syndrome
and ovarian hyperandrogenism. Rev Endocr Metab Disord
2009;10:63-76.
20. Holte J. Disturbances in insulin secretion and sensitivity in
women with the polycystic ovary syndrome. Baillieres Clin
Endocrinol Metab 1996;10:221-47.
21. Hollinrake E, Abreu A, Maifeld M, Van Voorhis BJ, Dokras A.
Increased risk of depressive disorders in women with polycystic
ovary syndrome. Fertil Steril 2007;87:1369-76.
22. Moran LJ, Pasquali R, Teede HJ, Hoeger KM, Norman RJ.
Treatment of obesity in polycystic ovary syndrome: a position
statement of the androgen excess and polycystic ovary syndrome
society. Fertil Steril 2009;92:1966-82.
23. Arslanian SA, Lewy VD, Danadian K. Glucose intolerance
in obese adolescents with polycystic ovary syndrome:  roles
of insulin resistance and beta-cell dysfunction and risk of
cardiovascular disease. J Clin Endocrinol Metab 2001;86:66-71.
24. Littlejohn EE, Weiss RE, Deplewski D, Edidin DV, Rosenfield
R. Intractable early childhood obesity as the initial sign of
insulin resistant hyperinsulinism and precursor of polycystic
ovary syndrome. J Pediatr Endocrinol Metab 2007;20:41-51.
25. Himelein MJ, Thatcher SS. Polycystic ovary syndrome and
mental health: a review. Obstet Gynecol Surv 2006;61:723-32.
26. Franks S. Polycystic ovary syndrome in adolescents. Int J Obes
(Lond) 2008;32:1035-41.
27. Weiner CL, Primeau M, Ehrmann DA. Androgens and mood
dysfunction in women: comparison of women with polycystic
ovarian syndrome to healthy controls. Psychosom Med
2004;66:356-62.
28. Jones G, Balen A, Ledger W. Health-related quality of life in
PCOS and related infertility:  how can we assess this? Human
Fertil 2008;11:173-85.
29. Dantzer R. Cytokine-induced sickness behavior: where do we
stand? Brain Behav Immun 2001;15:7-24.
30. Adali E, Yildizhan R, Kurdoglu M, Kolusari A, Edirne T,
Sahin HG, et al. The relationship between clinico-biochemical
characteristics and psychiatric distress in young women with
polycystic ovary syndrome. J Int Med Res 2008;36:1188-96.
31. Rasgon NL, Rao RC, Hwang S, Altshuler LL, Elman S,
Zuckerbrow-Miller J, et  al. Depression in women with
polycystic ovary syndrome: clinical and biochemical correlates.
J Affect Disord 2003;74:299-304.
[Downloaded free from http://www.jpbsonline.org on Sunday, November 7, 2021, IP: 182.253.163.99]

Sadeeqa, et al.: PCOS-related depression

32. Weber B, Lewicka S, Deuschle M, Colla M, Heuser I.
Testosterone, androstenedione and dihydrotestosterone
concentrations are elevated in female patients with major
depression. Psychoneuroendocrinology 2000;25:765-71.
33. Elsenbruch S, Benson S, Hahn S, Tan S, Mann K, Pleger K,
et  al. Determinants of emotional distress in women with
polycystic ovary syndrome. Hum Reprod 2006;21:1092-9.
34. Dixon JB, Dixon ME, O’Brien PE. Depression in association
with severe obesity: changes with weight loss. Arch Intern Med
2003;163:2058-65.
35. Motta B. Metformin in the treatment of polycystic ovary
syndrome. Cur Pharm Des 2008;14:2121-5.
36. Hahn S, Benson S, Elsenbruch S, Pleger K, Tan S, Mann K,
et  al. Metformin treatment of polycystic ovary syndrome
improves health-related quality-of-life, emotional distress and
sexuality. Hum Reprod 2006;21:1925-34.
37. Phillips KM, Antoni MH, Lechner SC, Blomberg BB,
Llabre MM, Avisar E, et al. Stress management intervention
reduces serum cortisol and increases relaxation during
treatment for nonmetastatic breast cancer. Psychosom Med
2008;70:1044-9.
38. Benson S, Arck PC, Tan S, Hahn S, Mann K, Rifaie N,
et  al. Disturbed stress responses in women with polycystic
ovary syndrome. Psychoneuroendocrinology 2009;34:
727-35.
39. Koulouri O, Conway GS. A systematic review of commonly
used medical treatments for hirsutism in women. Clin
Endocrinol (Oxf) 2008;68:800-5.
40. Knowler WC, Barrett-Connor E, Fowler SE, Hamman RF,
Lachin JM, Walker EA, et  al. Reduction in the incidence of
type 2 diabetes with lifestyle intervention or metformin. Scand
Med Sci in Spor 2003;13:208.
41. Farrell K, Antoni MH. Insulin resistance, obesity, inflammation,
and depression in polycystic ovary syndrome: biobehavioral
mechanisms and interventions. Fertil Steril 2010;94:
1565-74.

Journal of Pharmacy and Bioallied Sciences  ¦  Volume 10  ¦  Issue 2  ¦  April-June 2018 59