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American Journal of  Medical 
Science and Innovation (AJMSI) 

Serum Levels of  Thyroid Hormones in Infertile and Fertile Women Attending a Tertiary 
Care Hospital in North-Central Nigeria: A Comparative Reproductive Medicine Study

Halima Inya Aliu-Ayo1, Kikelomo Temilola Adesina2, Abiodun Akanbi Gafar Jimoh2, Aloysius Obinna Ikwuka3*

Francis Chigozie Udeh3, Sikiru Abayomi Biliaminu4, Olayinka Waheed Ayo5

Volume 2 Issue 2, Year 2023
ISSN: 2836-8509 (Online)

DOI: https://doi.org/10.54536/ajmsi.v2i2.2044
https://journals.e-palli.com/home/index.php/ajmsi

Article Information ABSTRACT

Received: August 28, 2023
Accepted: September 30, 2023
Published: October 14, 2023

Thyroid hormones have profound effects on reproduction. Normal thyroid function is 
necessary to maintain reproductive physiology, but its functional abnormalities may cause 
infertility manifesting as menstrual cycle irregularities. Aim of  this research was to determine 
the serum levels of  thyroid hormones in infertile and fertile women attending a tertiary care 
hospital in North-Central Nigeria. This comparative, reproductive medicine, cross-sectional 
study was carried out among one hundred and six (106) women attending the Gynecology 
Clinic of  the Department of  Obstetrics and Gynecology and the Family Planning Clinic 
of  a tertiary care hospital in North-Central Nigeria. Women with a history suggestive of  
either primary or secondary infertility and the control women with no history of  infertility 
were evenly grouped. Venous blood samples were collected and analyzed using Enzyme-
Linked Immunosorbent Assay (ELISA) technique to determine fT3, fT4 and TSH levels. 
Data obtained were entered and analyzed using Statistical Package for Social Sciences (SPSS) 
version 23, and the level of  statistical significance was set at p<0.05 and at a confidence 
interval of  95% for all inferential statistics. Majority (90.6%) of  the 106 participants were 
euthyroid. However, most of  the thyroid disorders (80%) were noticed in the infertile 
women, as 15.1% of  them had one form of  thyroid disorder. The mean TSH, fT3 and 
fT4 levels were higher in the infertile patients than in the control group, but the values 
were still within normal reference range. Mean values of  TSH, fT3 and fT4 for the patients 
and controls were 1.35±1.65 versus 0.85±1.08 mIU/mL, 2.79±1.51 versus 2.19±1.15 pg/
mL, and 1.15±0.33 versus 0.99 ± 0.29 ng/dL respectively. Median for TSH, fT3 and fT4 
in the patients and controls were as follows: 0.80 (0.40–1.55) versus 0.60 (0.40-0.85) mIU/
mL, 2.40 (1.45-4.20) versus 1.70 (1.35-2.95) pg/mL, and 1.10 (1.00-1.30) versus 1.00 (0.90- 
1.10) ng/dL respectively. The differences in the median between the patients and controls 
were statistically significant for fT3 and fT4 with p-values of  0.031 and 0.002 respectively. 
Subclinical hypothyroidism was the most prevalent (7.5%) thyroid disorder identified in the 
infertile women. Serum levels of  thyroid hormones and prevalence of  thyroid disorders 
were significantly higher in the infertile patients compared to the fertile women, although 
the overall prevalence of  thyroid disorders was quite low. 

Keywords
Thyroid Hormones, Thyroid 
Disorders, Female Infertility, 
Female Fertility, Reproductive 
Medicine, Comparative Study, 
Reproductive Endocrinology, 
Reproductive Gynecology

1 Department of  Obstetrics and Gynaecology, R-Jolad Hospital, Lagos, Nigeria
2 Department of  Obstetrics and Gynaecology, University of  Ilorin & University of  Ilorin Teaching Hospital,  Ilorin, Nigeria
3 College of  Medicine and Health Sciences, American International University West Africa, Banjul, The Gambia
4 Department of  Chemical Pathology and Immunology, University of  Ilorin & University of  Ilorin Teaching Hospital, Ilorin, Nigeria
5 The Bridge Clinic, Lagos, Nigeria
* Corresponding author’s e-mail: aloysiussweet@yahoo.com

INTRODUCTION
Gametes are ova and sperm cells that are haploid and 
have one copy of  each type of  chromosome i.e. 1–22 X 
or 1–22 Y (Ikwuka, 2023a). The sperm cell must fertilize 
an ovum in vivo or in vitro for conception (pregnancy) 
to occur. Infertility is a global health problem, a social 
demoralizing condition for couples and it is an important 
cause of  marital disharmony (Panti, 2014). It is defined 
as failure to achieve clinical pregnancy after 12 months 
(1 year) of  regular unprotected sexual intercourse – 
regular sexual intercourse is 2-3 times sexual intercourse 
per week (World Health Organization, 2010). Infertility 
can be further classified into primary infertility, in which 
no previous pregnancies have occurred and secondary 
infertility in which a prior pregnancy, although not 
necessarily a live birth, has occurred (Yao, 2002). The 
incidence of  infertility suggests that 10-15% couples 
experience infertility (Bhattacharya, 20007), constituting 

the major cause of  gynecological consultations in Nigeria 
(Jimoh, 2011; Obuna, 2012; Okonofua, 2005). One of  
the greatest desires of  couples is successful reproduction, 
especially in Africa, where a high premium is placed on 
childbearing. Infertility therefore causes severe emotional 
and social distress for the couple especially the social 
stigma attached to it in Africa (Gerias, 1992).
The endocrine system is the second key regulator of  
organ system function after the nervous system. The 
endocrine system uses hormones as chemical messengers 
in signaling, once stimulated. Upon stimulation, the 
thyroid gland secretes thyroid hormones (THs) which 
include tri-iodothyronine (T3) and thyroxine (T4). These 
hormones have a role in controlling basal metabolic rate 
(BMR), growth, and the development and differentiation 
of  many cells in the body (Habbu, 2016). Normal thyroid 
gland function is described as euthyroidism, below normal 
as hypothyroidism, and above normal as hyperthyroidism. 



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Hyperthyroidism has been linked with oxidative stress 
and various systemic immune inflammatory processes. 
In inducing oxidative stress, major free radicals that 
are of  physiological significance are superoxide anion, 
hydroxyl radical, and hydroperoxyl radical, while non-
radical is hydrogen peroxide (Ikwuka, 2023b). In addition, 
the interplay, role and effects of  metabolic syndrome 
diseases on female fertility are still being investigated 
by different researchers. Metabolic syndrome diseases, 
MSD (Hypertension, etc) are interrelated diseases with 
very high morbidity and mortality rates (Ikwuka, 2015; 
Ikwuka, 2017a; Ikwuka, 2017c; Ikwuka, 2023c; Virstyuk, 
2016). Results from different studies have shown that 
high levels of  blood pressure, glucose and lipid metabolic 
disorders, asymptomatic hyperuricemia, activation 
of  systemic immune inflammation and fibrogenesis, 
contribute to kidney damage (Ikwuka, 2017d; Ikwuka, 
2017e; Ikwuka, 2018a; Ikwuka, 2018c; Ikwuka, 2018d; 
Ikwuka, 2019a; Ikwuka, 2019c; Ikwuka, 2022; Ikwuka, 
2023d; Virstyuk, 2017a; Virstyuk, 2018a; Virstyuk, 2019; 
Virstyuk, 2021a; Virstyuk, 2021b). Adiposity, diabetes 
mellitus and dyslipidemia have also been linked with 
erectile dysfunction (Baysah, 2023).
Other than hormonal imbalance, several factors including 
hazards linked to certain occupations (long distance 
driving, military, etc); previous history of  genital infections 
(e.g. gonorrhea, orchitis, etc); previous history of  surgery 
in the genital tract or inguinal region; lifestyle choices 
(sedentary lifestyle, lack of  exercise, sleep deprivation, 
etc); environmental factors (e.g. exposure to ionizing 
radiation, pesticides, heat from tight underwears and hot 
baths) can adversely affect semen parameters and lead to 
male infertility (Baysah, 2023). In addition, lifestyles such 
as alcohol and tobacco consumption have been reported 
to cause infertility in men (Baysah, 2023). The effects of  
alcohol intake on semen quality have been reported to be 
caused by oxidative stress caused by an imbalance between 
Reactive Oxygen Species (ROS) produced by the alcohol 
consumed in the form of  free radicals that contain one or 
more unpaired electrons and antioxidants (Ekechi, 2023). 
Nicotiana tabacum (local snuff) has been reported to 
have adverse effects on fertility and pregnancy in female 
wistar rats (Udeh, 2023a; Udeh, 2023b).
An established association between thyroid dysfunctions 
and infertility exists. These dysfunctions in the form of  
hyper- or hypothyroidism can adversely affect fertility by 
the presence of  anovulatory cycles, luteal phase defects, 
high prolactin (PRL) levels, sex hormone imbalances, 
delayed onset of  puberty, menstrual abnormalities, and 
miscarriages (Doufas, 2000; Poppe, 2003; Poppe, 2007; 
Rijal, 2011). However, the relative frequency and the 
chronology of  the onset of  reproductive dysfunction 
concerning the onset and type of  thyroid disorder have 
not been well defined (Deshmukh, 2015).
Increasing evidence derived from experimental and 
clinical studies suggests that the hypothalamic-pituitary-
thyroid axis and hypothalamic-pituitary-ovarian axis 
are physiologically related. Thyroid hormones (THs) 
receptors and their mRNA have been detected in 

human granulosa cells and direct effects of  iodine and 
THs on ovarian function have been proposed recently 
(Poppe, 2003). TH scan directly affects granulosa cells, 
corpus luteum and oocytes (Biswas, 1993), and they 
regulate follicle-stimulating hormone (FSH) stimulation 
in follicles and prevent their apoptosis (Kabodmehri, 
2021). Thyroid-stimulating hormone (TSH) working 
in synergy with FSH can proliferate the granulosa cells 
(Kabodmehri, 2021). Therefore, an increase in TSH 
and thyrotropin-releasing hormone (TRH) can cause 
ovulatory dysfunction or corpus luteum dysfunction. 
In addition, the underperformance of  the thyroid gland 
can affect ovarian function indirectly by decreasing 
the binding activity of  sex hormone binding globulin 
(SHBG), increasing prolactin (PRL) levels and delaying 
luteinizing hormone (LH) response to gonadotropin-
releasing hormone (GnRH) (Lee, 2014).
The prevalence of  thyroid dysfunction in infertile 
women is quite high. In a study done at Aminu Kano 
Teaching Hospital, Kano, Nigeria; thyroid disorders were 
observed in 23.4% of  the subjects (Emokpae, 2011). The 
prevalence of  thyroid dysfunction in infertile women 
was found to be 33.3% in a study by (Rahman, 2008) in 
India and 23% by (Sharma, 2012) while (Shivaleela, 2012) 
found a prevalence of  42%. However, a study done in 
Port-Harcourt, Nigeria by (Orazulike, 2018) showed a 
much lower prevalence of  thyroid disorders in infertile 
women, which was 4.6%. 
Subclinical thyroid dysfunctions (i.e. subclinical 
hyperthyroidism or subclinical hypothyroidism) may go 
unnoticed by unwary clinicians because these patients 
do not exhibit clinically overt physical symptoms and 
signs. This may lead to avoidable surgical interferences 
and related complications. With the advent of  modern 
techniques, the estimation of  various hormones can 
be done rapidly and reliably. The diagnosis of  thyroid 
disorders can easily be made and appropriate treatment 
instituted with the results usually very gratifying.
Metabolic Syndrome Diseases require new and effective 
treatment regimens. Dapagliflozin which is a Sodium-
Glucose Linked Transporter 2 (SGLT-2) inhibitor and 
Liraglutide which is a Glucagon-like Peptide 1 Receptor 
Agonist (GLP-1 RA) have been found to increase the 
effectiveness of  treatment and improve the clinical 
course of  type 2 diabetes mellitus and hypertension 
in patients with such comorbidities (Ikwuka, 2017b; 
Ikwuka, 2018b; Ikwuka, 2019b; Ikwuka, 2021; Virstyuk, 
2017b; Virstyuk, 2018b; Virstyuk, 2018c). Rauwolfia 
vomitoria has a neuroprotective ability at it elevates 
antioxidants and suppresses lipid peroxidation (Ekechi, 
2023). Proper management of  thyroid dysfunction 
results in improvement in health status, normalization of  
menstrual abnormalities and restoration of  normal fertility 
(Micińsk, 2006). Therefore, it is very important to screen 
thyroid abnormalities in women with infertility, particularly 
in countries considered as areas with endemic goitre since 
female infertility associated with thyroid dysfunction in 
these areas is common (Zimmermann, 2008).



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MATERIALS AND METHODS
Study Setting
This study was conducted at the Gynecology Clinics of  
the Department of  Obstetrics and Gynecology of  the 
University of  Ilorin Teaching Hospital (UITH), Ilorin, 
Kwara State, North-Central Nigeria. UITH is located at 
Oke-Oyi, Old Jebba Road in Ilorin. The hospital serves 
as a major referral centre for Kwara State and parts of  
the nearby states of  Oyo, Osun, Ekiti, Kogi and Niger. 
UITH is a tertiary care hospital, although it also offers 
primary and secondary healthcare services, and it is 
approved to undertake undergraduate and postgraduate 
medical training. The Gynecology Clinic is open to all, 
and an average of  144 women access healthcare at the 
clinics weekly, with 25% of  them being for infertility 
cases (follow-up and new cases).

Study Population
The study population consisted of  reproductive age 
women (18-45 years) attending the Gynecology Clinic 
of  UITH, and with a history of  inability to conceive of  
more than one year duration. This included those with 
previous pregnancies irrespective of  outcome (secondary 
infertility) and those with no previous pregnancy (primary 
infertility). The control group consisted of  consenting 
fertile women, who had carried pregnancy to term within 
two years prior to this study, and who were new patients 
at the Family Planning Clinic of  UITH.

Sample Size and Sampling Technique
The formula for sample size calculation for a comparative, 
cross-sectional study was used (Charan, 2013). The 
parameter, proportion of  thyroid disorders in women, 
was extracted from a previous study by (Fatima, 2014).
N=  (2(Z(α/2)+ Zβ )

2  ˟ P(1-P))/(P1-P2 )
2 

N= Sample size
Z(α/2)= 1.96 at type 1 error of  5%
Zβ= 1.28 at 90% power 
P1= Proportion of  thyroid disorder in infertile women  
(47%)
P2= Proportion of  thyroid disorder in fertile women 
(16%). P1 and P2 were extracted from a previous study by 
(Fatima, 2014).
P= Pooled prevalence = [prevalence in one group (P1) + 
prevalence in another group (P2)]/ 2
P= [(0.47 + 0.16) / 2] = 0.32
N= (2(1.96+ 1.28)2  ˟ 0.32(1-0.32))/(0.47-0.16)2 

N= 2(10.497)(0.2176)/(0.31)2 
N= 2(10.497)(0.2176)/0.0961
N= 47.5
N~ 48 patients
To make provision for attrition, 10% of  the sample size 
was added. Thus 53 women in each arm of  the study, and 
a total sample size of  one hundred and six (106) women 
were recruited for the study. Respondents (patients and 
controls) were recruited consecutively till the sample size 
was complete.

Inclusion Criteria
Study participants were consenting women of  
reproductive age group (18-45 years) with primary 
or secondary infertility. Control group consisted of  
consenting fertile women matched for age. The control 
group members were new clients at the Family Planning 
Clinic, apparently healthy, with no history of  infertility, 
have carried a pregnancy to term, and had no record of  
contraceptive use two years prior to this study.

Exclusion Criteria
Female patients outside the age group of  18-45 years; with 
previous or present thyroid disorders; women on steroids, 
hormonal contraceptives, or intrauterine contraceptive 
devices; women with a history of  bleeding disorders; 
women with co-existing uterine fibroids (leiomyoma uteri).

Data Collection Method
The study spanned 6 months. Patients who presented 
with infertility were selected based on the inclusion 
criteria. Eligible women were informed and counseled 
about the study in a simple language that they understood. 
The study proforma was designed to obtain respondents’ 
socio-demographic status, history of  infertility, history 
of  anterior neck swelling and other symptoms suggestive 
of  thyroid disorder, medical conditions and past surgical 
procedures.

Sample Collection
Four milliliters (4ml) of  whole blood sample was 
collected from a peripheral vein from each participant 
after an overnight fast of  8-10 hours into a labeled plain 
sample bottle. Food affects TSH levels, TSH decreases 
postprandial and a possible explanation for this is 
food-induced elevation of  circulating somatostatin and 
consequent suppression of  TSH (Takano, 1995). Patients 
who had coincidentally fasted for 8-10 hours at the first 
contact with the researcher were recruited while those who 
had already eaten were recruited at their next visit after 
they had been informed. Blood samples were allowed to 
stand for about 1-2 hours to allow clotting and retraction. 
The sera was drained from the clot and later centrifuged 
at 1,000 revolutions per minute (rpm) for 10 minutes. The 
whole sera obtained was transferred into labeled plain 
containers and kept frozen at -20ºC before analysis.

Laboratory Procedures
Serum concentrations of  TSH, fT3 and fT4 were 
determined by using Enzyme-linked immunosorbent assay 
(ELISA) kits manufactured by Monobind Ltd using Rayto 
microplate well reader. All reagents, calibrators/ standards 
and patients’ specimens were brought to room temperature 
(20-27ºC). The microplate wells for each calibrator/
standard and patient specimen were formatted, and the 
following steps described by (Winter, 2012) were taken:

1. 50μl of  the calibrator and the patient specimen were 
dropped into the assigned well with a pipette.



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2. 100μl of  TSH, fT3, and fT4 enzyme reagent was 
added to each well.

3. The microplate was swirled gently for 20-30 seconds 
and then incubated for 60 minutes at room temperature. 

4. The contents of  the microplate were discarded by 
decantation, and the plate was tapped and blotted dry 
with absorbent paper.

5. 350μl of  wash buffer was added followed by 
decantation, a process that was repeated 2 additional times. 

6. 100μl of  working substrate solution was added to all 
wells without shaking the plates. This was incubated for 
15 minutes at room temperature.

7. 50μl of  stop solution was added to each well and 
mixed for 15-20 seconds. 

8. The absorbance/optical density was read in each 
well at 450nm. The results were read within 30 minutes 
of  adding the stop solution.

9. Calibration curves were plotted for each analyte to 
determine the corresponding concentration of  these 
analytes in the patients’ samples.

Criteria for Diagnosis of  Thyroid Dysfunction
The reference range of  values for THs that was used 
for this study is the range of  normal values on the kit 
used (TSH: 0.39-6.16 mIU/mL; fT3: 1.4-4.2 pg/mL; and 
fT4: 0.7-2.0 ng/dL) (Monobindinc, 2012a; Monobindinc, 
2012b; Monobindinc, 2012c). Abnormal thyroid function 
can be categorized as hyperthyroidism (elevated fT3, fT4, 
and decreased TSH), hypothyroidism (decreased fT3, fT4, 
and elevated TSH), subclinical hyperthyroidism (normal 
fT3, fT4, but low TSH), and subclinical hypothyroidism 
(normal fT3, fT4, but elevated TSH) (Habbu, 2016).

Data Analysis
Data was analyzed using Statistical Package for Social 
Sciences (SPSS) version 23. Categorical variables (thyroid 
disorders) were presented as proportions and analyzed 
using the Chi-square test with Fisher’s exact correction 

used in cases where more than 20% of  expected counts 
were less than 5. The continuous variable that is normally 
distributed (like age) was presented as mean and analyzed 
using the T-test while those that were not normally 
distributed  (the THs levels) were presented as median 
and interquartile range and analyzed using the Mann-
Whitney U test. The test of  normality was done using 
the Shapiro-Wilk test. The level of  statistical significance 
was set at p<0.05 at a confidence interval of  95% for all 
inferential statistics.

Ethical Considerations
Ethical approval for this study was obtained from the 
Ethical Review Committee of  UITH. Informed written 
consent was obtained from each participant after adequate 
counseling and all data from the study were treated with 
confidentiality and used solely for the study. Patients with 
thyroid abnormalities were referred for further evaluation, 
treatment, and were co-managed with endocrinologists.

RESULTS AND DISCUSSION
The findings in the one hundred and six (106) study 
participants are as shown below.

Socio-Demographic Variables of  Participants
Table 1 shows the socio-demographic variables of  the 
infertile women and control group. Women in the age 
group 25-28 years had the highest frequency of  30.2%, 
while women below 25 years of  age had the lowest 
frequency of  13.2%. The mean age for the infertile and 
control group was 32.18±6.47 years and 31.4±5.74 years 
respectively. The majority of  the patients and control 
(79.2% and 81.1%) respectively were employed. The 
majority of  the study participants had a tertiary level 
of  education (69.8%) and were Yorubas (83%). There 
were no significant differences in the age, occupation, 
educational status and ethnicity of  the study participants 
in the two groups.

Table 1: Socio-demographic variables of  the infertile women (patients) and fertile (control) group
Socio-demographic variable Patient n (%) Control n (%) Total n (%) χ2/ t p-value
Age (years)
< 25 9 (17.0) 5 (9.4) 14 (13.2) 2.932 0.569
25 – 29 14 (26.4) 18 (34.0) 32 (30.2)
30 – 34 7 (13.2) 11 (20.8) 18 (17.0)
35 – 39 15 (28.3) 12 (22.6) 27 (25.5)
40 – 45 8 (15.1) 7 (13.2) 15 (14.2)
Total (n) 53 53 106
Age (Mean ± SD)* 32.18±6.47 31.40±5.74 0.651t 0.516
Occupational status
Employed 42 (79.2) 43 (81.1) 85 (44.3) 0.509 0.808
Unemployed 11 (20.8) 10 (18.9) 21 (19.8)
Total (n) 53 53 106
Educational status
None 1 (1.9) 1 (1.9) 2 (1.9) 1.784f 0.759



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Gynecological Variables and Symptoms Found 
among the Infertile and the Fertile Groups
Figure 1 illustrates the types of  infertility found among 
the infertile patients. Secondary infertility was identified 
in 75.5% of  the infertile women while 24.5% had primary 
infertility.

Table 2 illustrates the symptoms present in the infertile 
patients and the control (fertile) group. None of  the 
participants presented with anterior neck swelling. Two 
(3.8%) of  the infertile patients experienced palpitations 
compared to three (5.7%) in the control group. Only one 
(1.9%) patient lost weight as against none in the control. 
Four (7.5%) patients had a history of  abnormal weight 
gain as against two (3.8%) in the control group. Previous 
history of  miscarriages was more prominent in infertile 
women (30.2%) than in fertile women (7.5%). Heat or 
cold intolerance was only evident among the infertile 
women (3.8%), and this group had more members 
(7.5%) with decreased libido than 1.9% seen in the 
control group. Of  all these symptoms, only previous 
miscarriages presented a significant difference (p-value 
= 0.003) between the two groups.

Primary 1 (1.9) 2 (3.8) 3 (2.8)
Secondary 16 (30.2) 11 (20.8) 27 (25.5)
Tertiary 35 (66.0) 39 (73.6) 74 (69.8)
Total (n) 53 53 106
Ethnicity
Yoruba 45 (84.9) 43 (81.1) 88 (83.0) 1.137f 0.822
Hausa 2 (3.8) 1 (1.9) 3 (2.8)
Igbo 2 (3.8) 3 (5.7) 5 (4.8)
Others 4 (7.5) 6 (11.3) 10 (9.4)
Total (n) 53 53 106

χ2: Chi square; t: Independent Samples T test; f: Fisher’s exact test

Figure 1: Types of  infertility among the participants

Table 2: Symptoms found in women with infertility (patients) and the control (fertile) group
Variables Patient n (%) Control n (%) Total n (%) χ2 p-value
Anterior neck swelling 
No 53 (100.0) 53 (100.0) 106(100.0)
Palpitations 
Yes 2 (3.8) 3 (5.7) 5 (4.7) 0.210f 1.000
No 51 (96.2) 50 (94.3) 101 (95.3)
Weight loss
Yes 1 (1.9) 0 (0.0) 1 (0.9) 1.010f 1.000
No 52 (98.1) 53 (100.0) 105 (99.1)
History of  abnormal weight gain
Yes 4 (7.5) 2 (3.8) 6 (5.7) 0.707f

No 49 (92.5) 51 (96.2) 100 (94.3) 0.678
Previous miscarriage
Yes 16 (30.2) 4 (7.5) 20 (18.9) 8.874
No 37 (69.8) 49 (92.5) 86 (81.1) 0.003*
Heat or cold intolerance
Yes 2 (3.8) 0 (0.0) 2 (1.9) 2.038f

No 51 (96.2) 53 (100.0) 104 (98.1) 0.495
Decreased libido 
Yes 4 (7.5) 1 (1.9) 5 (4.7) 1.889f

No 49 (92.5) 52 (98.1) 101 (95.3) 0.363
χ2: Chi square test; f: Fisher’s exact test; *: p-value <0.05



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Comparison of  the Serum Levels of  Thyroid 
Hormones and Thyroid Dysfunctions in the Infertile 
Patients and the Control (Fertile) Group
Table 3 compares the serum levels of  thyroid hormones 
of  infertile and fertile women. The mean TSH, fT3 and 
fT4 levels were higher in the infertile women than in the 
fertile women with mean values of  1.35±1.65 versus 
0.85±1.08 mIU/mL for TSH, 2.79±1.51 versus 2.19±1.15 

pg/mL for fT3, and 1.15±0.33 versus 0.99±0.29 ng/dL 
for fT4. A significant difference was only in fT3 (p-value 
= 0.023) and fT4 (p-value = 0.009). The median for TSH, 
fT3 and fT4 was higher in the infertile group than in the 
fertile group, although only significant in fT3 (p-value = 
0.031) and fT4 (p-value = 0.002). The lower and upper 
limits of  the three parameters were within the normal 
reference range.

Table 3: Comparison of  thyroid hormone levels of  patients with infertility and the control (fertile) group
Variables Patients Control U p-value
TSH (mIU/mL)
Mean ± SD 1.35±1.65 0.85±1.08 1149.000 0.064
Median (IQR) 0.80 (0.40-1.55) 0.60 (0.40-0.85) 0.105
fT3 (pg/mL)
Mean ± SD 2.79±1.51 2.19±1.15 1062.500 0.023*
Median (IQR) 2.40 (1.45-4.20) 1.70 (1.35-2.95) 0.031*
fT4 (ng/dL)
Mean ± SD 1.15±0.33 0.99±0.29 924.000 0.009*
Median (IQR) 1.10 (1.00-1.30) 1.00 (0.90-1.10) 0.002*

U: Mann-Whitney U test; *: p-value <0.05

Table 4: Prevalence of  thyroid disorders among the infertile women (patients) and the control (fertile) group
Variable  Patient n (%) Control n (%) Total n (%) χ2 p-value OR (95% CI)
Thyroid disorders
 Present 8 (15.1) 2 (3.8) 10 (9.4) 3.975f 0.046* 4.533 (0.915 – 22.465)
 Absent  45 (84.9) 51 (96.2) 96 (90.6)

χ2: Chi square; OR: Odds ratio; 95% CI: 95% Confidence interval; *: p- value <0.05

Table 4 demonstrates the prevalence of  thyroid disorders 
among the infertile women (patients) and the control 
(fertile) group.  Eight (15.1%) patients had thyroid 
disorders compared to two (3.8%) in the control group, a 
difference statistically significant (p-value = 0.046). Forty-
five (84.9%) infertile and 51 (96.2%) fertile women were 
euthyroid.
Table 5 compares the pattern of  thyroid disorders among 
infertile and fertile women. Four (7.5%) of  the infertile 
women had subclinical hypothyroidism while one (1.9%) 
of  the fertile women had subclinical hypothyroidism, 
and the difference was not significant (p-value = 0.37). 
Overt i.e. clinical hypothyroidism was present in two of  
the infertile patients but was absent in the fertile women. 
Overt i.e. clinical hyperthyroidism was present in two of  
the infertile women while only one of  the fertile women 

had it, and the difference was not significant (p-value = 
1.000). Majority of  the study participants were euthyroid 
– as observed in 45 (84.9%) of  the infertile women as 
against 51 (96.2%) in the fertile women.
Table 6 shows the association between thyroid dysfunction 
and menstrual cycle abnormality. Five (62.5%) out of  
eight infertile women with thyroid dysfunction had 
menstrual irregularities, and others (37.5%) had normal 
menses. Thirteen (28.9%) out of  forty-five euthyroid 
infertile women had menstrual irregularities, and others 
(71.1%) had normal menses. Of  the two fertile women 
with a thyroid disorder, one had a menstrual anomaly and 
the others did not. Six (11.8%) of  the fifty-one euthyroid 
fertile women had menstrual irregularities, while others 
(45) did not. These differences were not statistically 
significant (p-value >0.05).

Table 5: Pattern of  thyroid dysfunction among infertile women and control (fertile) women 
Thyroid disorder Patients n (%) Control n (%) Total n (%) χ2/ t p-value
Subclinical hypothyroidism 4 (7.5) 1 (1.9) 5 (4.7) 0.800 0.371
Overt (clinical) hypothyroidism 2 (3.8) 0 (0.0) 2 (1.9) NA
Overt (clinical) hyperthyroidism 2 (3.8) 1 (1.9) 3 (2.8) 0.000 1.000
None 45 (84.9) 51 (96.2) 96 (90.6) 0.260 0.610
Total 53 53 106

χ2: Chi-square; NA: Chi-square not available because of  zero ‘0’ value



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Table 6: Association between thyroid dysfunction and menstrual cycle abnormality
Thyroid disorder Menstrual abnormality

Present Absent Total χ2 p-value OR (95% CI)
n (%) n (%) n (%)

Patient
Present 5 (62.5) 3 (37.5) 8 3.421f 0.104 4.103 (0.854 – 19.716)
Absent  13 (28.9) 32 (71.1) 45
Total 18 35 53
Control 
Present 1 (50.0) 1 (50.0) 2 2.454 0.249f 7.500 (0.413 - 136.271)
Absent  6 (11.8) 45 (88.2) 51
Total 7 46 53

χ2: Chi square; OR: Odds ratio; 95% CI: 95% Confidence interval

Undiagnosed and untreated thyroid disease can be a cause 
of  infertility as well as sub-fertility which have important 
medical, economic, and psychological implications 
in our society (Verma, 2012). Aside from infertility, 
thyroid dysfunction could cause other reproductive 
disorders such as abnormal sexual development or 
menstrual irregularities. Even in fertility, pregnancy can 
be complicated by anemia due to SCD and despite the 
significant need for effective treatment options for SCD 
patients, current treatments both traditional and newly 
developed, only ameliorate acute and chronic SCD 
manifestations without addressing the underlying cause 
(Musa, 2023).
Of  the infertile women, 75.5% had secondary infertility 
and 24.5% primary infertility. This is consistent with 
the findings of  (Panti, 2014) which reported that 
67.2% infertile female patients had secondary infertility 
and 32.8% had primary infertility. This dominance of  
secondary infertility in this study agrees with previous 
studies in Africa (Bala, 2003; Ekanem, 2006; Obuna, 
2012; Okonofua, 2003), but contrasts the finding in most 
Western societies where primary infertility dominate with 
63.1-80.0% (Habbu, 2016; Nasir, 2016).
In this study, 30.2% of  infertile patients had previous 
miscarriages, a value close to the 37% reported by 
(Orazulike, 2018). Previous miscarriage was the only 
pregnancy outcome reported in their study by its design. It 
was also reported by the patient with some possible recall 
bias. Notwithstanding, this suggests that subfertility and 
pregnancy wastage are associated with thyroid disorders 
in women. Other symptoms presented by the subjects 
were palpitation (3.8%), weight loss (1.9%), abnormal 
weight gain (7.5%), heat/cold intolerance (3.8%), and 
decreased libido (7.5%). None of  the 106 participants 
had anterior neck swelling.
The mean serum levels of  thyroid hormones (TSH, fT3 
and fT4) in this study were within the normal reference 
range although higher in the infertile women. The overall 
prevalence of  thyroid disorders was 15.1% and 3.8% 
in the infertile and fertile women respectively. A similar 
study done in Port-Harcourt, Nigeria by (Orazulike, 2018) 

found a much lower prevalence of  thyroid disorders of  
4.6% in infertile women. Similar studies done in India by 
(Rahman, 2008) and another by (Rijal, 2011) reported a 
prevalence of  25.6% and 33.0% respectively.  Similarly, 
(Habbu, 2016), (Sharma, 2012), and (Shivaleela, 2012) 
reported higher prevalence rates (between 23.0- 42.3%) 
of  thyroid disorders in infertile women. Thyroid 
hormone synthesis is influenced by iodine and it varies 
from clime to clime depending on water, soil, diet and 
fortification (Utiger, 2006). With this knowledge, the 
difference in the prevalence of  thyroid disorders in these 
studies can therefore be related to the variation in the 
study particpants’ consumption of  iodine-containing 
meals (Elahi, 2007). 
TSH was higher, but fT3 and fT4 levels were significantly 
higher when serum levels of  thyroid hormones of  the 
patients are compared with that of  the control group. 
(Habbu, 2016) and (Shivaleela, 2012) also reported 
findings of  elevated mean serum fT3 and fT4 but low 
TSH in the infertile patients. (Orazulike, 2018) found no 
significant difference in the mean serum fT3, fT4, TSH, 
and TPOAb between patients and controls. These findings 
were different from the findings of  (Fatima, 2014) where 
serum fT3 and fT4 were significantly decreased and 
serum TSH was significantly increased in infertile females 
when compared with fertile females. Serum fT3 and fT4 
may be higher where a large proportion of  the patients 
are hyperthyroid and the reverse may be the case when a 
large proportion of  the patients are hypothyroid.
On types of  thyroid dysfunction in this study, 9.4% 
had one type of  thyroid dysfunction and 90.6% were 
euthyroid. In agreement with this, (Elahi, 2007) reported 
that 89.3% infertile patients and 93.4% fertile control 
were euthyroid. This finding is consistent with that of  
(Goswami, 2009), (Orazulike, 2018), and (Rijal, 2011). 
With infertile women being euthyroid, this suggests that 
other cause(s) of  infertility aside from thyroid disorders 
should be evaluated during infertility examination as there 
can be significant single or multiple causes of  infertility.
Subclinical hypothyroidism was the most predominant 
thyroid disorder in this study. A study done in Kano 



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Nigeria by (Emokpae, 2011) got a higher prevalence 
(14.9%) for subclinical hypothyroidism as against the 9.4% 
in this present study. This may be because Emokpae’s 
study assessed only TSH in hyperprolactinemic women 
focusing only on subclinical thyroid diseases while overt 
(clinical) thyroid diseases were not considered at all. 
Hypothyroidism is associated with increased production 
of  TRH, which stimulates the anterior pituitary to 
secrete TSH and prolactin. Hyperprolactinemia adversely 
affects fertility potential by impairing GnRH pulsatility 
and thereby affecting ovarian function (Poppe, 2003). 
Therefore, it is advisable to check TSH and PRL levels 
in every infertile female, regardless of  their menstrual 
rhythm (Abdul, 2015). Moreover, concerning subclinical 
hypothyroidism (Poppe, 2003) reported a prevalence of  
0.9% and (Bohnet, 1981) reported a prevalence of  11%.
The prevalence of  subclinical hypothyroidism in 
subfertile women has been reported to vary from 
0.7% to 43% (Poppe, 2007). This wide range is due 
to the differences in the sensitivity of  serum TSH 
measurement. The revised clinical practice guidelines 
of  the Endocrine Society recommend the measurement 
of  serum TSH in women over the age of  30 years with 
infertility or a prior history of  miscarriage, to screen for 
thyroid dysfunction (De Groot, 2012). In clinical practice 
guidelines for hypothyroidism in adults, the American 
Association of  Clinical Endocrinologists (AACE) 
and the American Thyroid Association (ATA) have 
recommended that treatment with L-thyroxine should be 
considered in women of  childbearing age with subclinical 
hypothyroidism when they are planning a pregnancy 
(Garber, 2012). If  infertile women planning pregnancy 
are diagnosed with subclinical hypothyroidism as well as 
overt (clinical) hypothyroidism, they are recommended 
to be treated to reduce risks of  miscarriage and fetal 
developmental impairment or to improve the in vitro 
fertilization outcome (Lee, 2014). Evidence suggests that 
treating thyroid disorders and keeping TSH levels below 
2.5 mIU/L may improve conception rates in infertile 
women and reduce early pregnancy loss (Garber, 2012). In 
the study by (Bohnet, 1981), subclinical hypothyroidism 
was considered an infertility factor by itself  because 
treatment with L-thyroxine 50 mg/day normalized the 
mid-progesterone secretion and two out of  the eleven 
treated women became pregnant.
Thyroid disorders have a known association with 
menstrual irregularities which may lead to infertility 
(Krassas, 1990). In this study, menstrual irregularities 
were significantly more predominant in the infertile 
patients than in the fertile control and 62.5% of  the 
infertile patients with thyroid disorders had menstrual 
irregularities. (Orazulike, 2018) reported menstrual 
irregularities in 50% of  the patients. (Nasir, 2016) 
also reported menstrual irregularities in 19.6% of  the 
patients. (Goswami, 2009) similarly reported menstrual 
irregularities in 61.2% of  the infertile patients and that 
50% infertile patients with hypothyroidism had menstrual 
irregularities.

The impact of  hypothyroidism on ovulation and 
menstrual function is related to numerous interactions of  
thyroid hormones with the female reproductive system, 
in turn causing infertility. In hypothyroidism, increased 
TRH production leads to hyperprolactinemia and altered 
gonadotropin-releasing hormone (GnRH) pulsatile 
secretion. This leads to a delay in luteinizing hormone 
(LH) response and inadequate corpus luteum leading to 
abnormal follicular development and ovulation. At the 
cellular level, thyroid hormone receptors are expressed 
in human oocytes and granulosa cells, and the hormones 
synergize with the follicle-stimulating hormone-mediated 
luteinizing hormone/human chorionic gonadotropin 
(hCG) receptor to exert direct stimulatory effects on 
granulosa cell function of  progesterone production 
(Poppe, 2004). Altering the peripheral metabolism of  
estrogen and decreasing sex hormone-binding globulin 
(SHBG) production is another pathway by which 
hypothyroidism may impact on fertility. These pathways 
may result in abnormal feedback at the pituitary level and 
consequently infertility (Bassey, 2015). 
Several aspects of  the reproductive axis influenced by 
hyperthyroidism are comparable with the situation in 
hypothyroid women. In hyperthyroidism, the SHBG 
production, the conversion of  androgens to estrogens, 
and the gonadotrophin response to GnRH are increased. 
The decrease in menstrual flow may also be related to 
effects on hemostatic factors, including the synthesis of  
factor VIII (Krassas, 2000). Women with hyperthyroidism 
and fertility problems should be treated with antithyroid 
drugs and/or surgery according to the cause of  
hyperthyroidism (Krassas, 2000).

CONCLUSION
Serum levels of  thyroid hormones and the prevalence 
of  thyroid disorders were significantly higher in the 
infertile patients when compared with the fertile women. 
Although the overall prevalence was quite low, thyroid 
abnormalities could still be implicated as a cause of  
female infertility. It is recommended that all infertile 
women should have thyroid function tests as part of  their 
infertility work-up as many patients with thyroid diseases 
can easily be missed if  they are not screened. Direction 
for future research on this topic would be to evaluate the 
menstrual pattern and irregularities and relate these to 
thyroid disorder patterns among women within this study 
setting. This will give a clearer picture of  the relationship 
between symptoms of  menstrual irregularities and 
thyroid dysfunction which varies from region to region.

Acknowledgments 
Special thanks to all the infertile and fertile women who 
voluntarily participated in this study after making an 
informed decision.

Authors’ Contribution
All authors contributed in different aspects of  the 
research.



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Am. J. Med. Sci. Innov. 2(2) 141-152, 2023

Conflict of  Interest
The authors guarantee responsibility for everything 
published in this manuscript, as well as the absence of  
a conflict of  interest and the absence of  their financial 
interest in performing this research and writing this 
manuscript.

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