|Year : 2022 | Volume
| Issue : 2 | Page : 43-48
Effect of omega-3 supplementation on serum adiponectin and fertility hormones in women with polycystic ovarian syndrome
Onyema A Onyegbule1, Samuel Chukwuemeka Meludu1, Chudi Emmanuel Dioka1, John E Okwara1, Chikaodili Nwando Obi-Ezeani2, Chidiadi M Njoku1, Ejike Christian Onah3
1 Department of Chemical Pathology, Nnamdi Azikiwe University, Nnewi, Nigeria
2 Department of Chemical Pathology, Chukwuemeka Odumegwu Ojukwu University, Awka, Anambra, Nigeria
3 Department of Medical Laboratory Sciences, Nnamdi Azikiwe University, Nnewi, Nigeria
|Date of Submission||26-Jan-2022|
|Date of Decision||23-Mar-2022|
|Date of Acceptance||26-Jan-2022|
|Date of Web Publication||15-Jun-2022|
Chikaodili Nwando Obi-Ezeani
Department of Chemical Pathology, Chukwuemeka Odumegwu Ojukwu University, Awka, Anambra
Source of Support: None, Conflict of Interest: None
Background: Polycystic ovarian syndrome (PCOS) is the most common endocrinopathy affecting women of reproductive age with prevalence of about 4%–20%. Aim: This study aims to evaluate serum adiponectin and fertility hormones in women with PCOS, and the subsequent effect of omega-3 supplementation. Subjects and Methods: One hundred and fifty women aged 18–40 years were assigned into groups A and B comprising women with PCOS and control, respectively. Group A was further subdivided into groups 1 and 2 receiving omega-3 and placebo daily for 12 weeks, respectively. Blood samples were collected before and after 12 weeks of supplementation for analysis of adiponectin, follicle stimulating hormone (FSH), luteinizing hormone (LH), testosterone, prolactin, estradiol, progesterone, and sex hormone binding globulin (SHBG). Statistical Package for Social Sciences (SPSS) version 23.0 was used for data analysis, and the level of statistical significance was set at P < 0.05. Results: Serum adiponectin, progesterone, and SHBG were significantly lower while FSH, LH, testosterone, prolactin, and estradiol were significantly higher in women with PCOS when compared with the control (P < 0.05). Adiponectin and progesterone levels increased significantly while FSH, LH, testosterone, prolactin, and estradiol levels decreased significantly after 12 weeks of omega-3 supplementation when compared with the levels at baseline as well as when compared with those on placebo (P < 0.05). Statistical Package for Social Sciences (SPSS) version 23.0 was used for data analysis. Conclusion: Omega-3 may be beneficial in improving certain hormonal alterations in women with PCOS. Omega-3 supplements may therefore be used as part of the regimen in the management of patients with PCOS.
Keywords: Adiponectin, estradiol, follicle stimulating hormone, luteinizing hormone, omega-3, testosterone
|How to cite this article:|
Onyegbule OA, Meludu SC, Dioka CE, Okwara JE, Obi-Ezeani CN, Njoku CM, Onah EC. Effect of omega-3 supplementation on serum adiponectin and fertility hormones in women with polycystic ovarian syndrome. J Appl Sci Clin Pract 2022;3:43-8
|How to cite this URL:|
Onyegbule OA, Meludu SC, Dioka CE, Okwara JE, Obi-Ezeani CN, Njoku CM, Onah EC. Effect of omega-3 supplementation on serum adiponectin and fertility hormones in women with polycystic ovarian syndrome. J Appl Sci Clin Pract [serial online] 2022 [cited 2022 Jul 4];3:43-8. Available from: http://www.jascp.com/text.asp?2022/3/2/43/347597
| Introduction|| |
Polycystic ovarian syndrome (PCOS) is the most common endocrinopathy affecting women of reproductive age, and has a worldwide prevalence of about 4%–20%. PCOS is multifaceted, with accompanying metabolic, endocrine and reproductive disorders, causing adverse health outcomes across all ages, and is a major public health concern. It is accompanied with increased ovarian and adrenal androgen secretion, and subsequently hirsutism, acne, alopecia, menstrual irregularity as well as polycystic ovaries.,
In other words, it may be regarded as a chronic systemic disease commonly associated with hyperandrogenemia, insulin resistance, chronic inflammation, and oxidative stress; however, the pathogenetic mechanism has not been well-defined. PCOS accounts for 90% of women with oligomenorrhea (infrequent periods), 30% with amenorrhea (absence of periods), and over 70% of women with anovulation.
The adipose tissue which is assumed to be the largest endocrine organ in the body, secretes a large number of biologically important substances termed adipokines including adiponectin which plays various essential roles.
Omega-3 polyunsaturated fatty acids (Omega-3 PUFA) are fatty acids which are beneficial to health and helps in the prevention of certain disorders including cardiovascular disease, cancer, inflammatory, thrombotic and autoimmune diseases as well as improve various metabolic disorders such as hyperinsulinemia, insulin resistance, and dyslipidemia associated with PCOS. There are limited data on the effect of omega-3 on PCOS in our locality, hence, this study was designed to evaluate serum adiponectin and fertility hormones in women with PCOS attending Federal Medical Centre, Owerri in Imo State, Nigeria, and the subsequent effect of supplementing with omega-3 PUFA.
| Subjects and Methods|| |
This is a case–control study followed by an intervention study. It comprised 150 women attending the Obstetrics and Gynecology Clinic of Federal Medical Centre (FMC) Owerri in Imo State, Nigeria, and between the ages of 18 and 40 years. The case–control study consisted of 2 groups (A and B) of 75 participants each. Group A included women diagnosed with PCOS (cases) using Rotterdam criteria, and group B included age-matched women without PCOS (control). The intervention study involved the 75 women with PCOS (in group A) who were further subdivided into two groups (1 and 2) of 38 and 37 participants, respectively. Group 1 received omega-3 supplements while group 2 received placebo daily for 12 weeks, between March and May 2019.
Sample size was calculated using the formula; n = 2Z2PQ/d2.
Where n = sample size
Z = standard normal deviation at 95%confidence interval which is 1.96
d = degree of precision (0.05)
P = proportion of the target population (2.2%)
Q = alternate proportion (1-p); 1-0.022 = 0.978
The prevalence of PCOS patients in Nnewi is 2.2%, and is used as the proportion of the target population (P).
Minimum sample size is 68, plus 10% attrition (≃ 7) =75.
Therefore, sample size = 75.
Consenting participants who met with the Rotterdam criteria for PCOS diagnosis and nonpregnant premenopausal women between the ages of 18 and 40 years were included in the study whereas women who were pregnant or breastfeeding, nonpregnant women on any form of hormonal contraceptive, lipid or glucose lowering drugs, weight reducing agents or glucocorticoids as well as women with hyperprolactinemia were excluded from the study.
Approval for this study was obtained from the Health Research and Ethics Committee of FMC, Owerri with the approval number FMC/OW/HREC/191. Written informed consents were obtained from the participants prior to enrolment into the study, and procedures followed were in accordance with ethical standards and the Helsinki Declaration.
Each capsule of omega-3 (Strides Arcolab Ltd, India) contained 180 mg of eicosapentaenoic acid and 120 mg of docosahexaenoic acid, while each capsule of placebo contained 1 g of paraffin. All participants were followed up weekly by phone calls, and were seen at the clinic every 2 weeks to restock on the supplements (depending on the group) to ensure compliance in taking the supplements. All participants were asked to maintain their usual diet and lifestyle habits.
Five milliliters of blood sample was collected from each participant between 8.00 am and 10.30 am, dispensed into plain vacutainer tubes, centrifuged at 5000 rpm for 5 min, and the sera obtained used for analyses of serum adiponectin, follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone (Tt), prolactin (PRL), estradiol (E2), progesterone, and sex hormone binding globulin (SHBG). The blood samples were collected prior to intervention (at baseline) and after 12 weeks of omega-3 and placebo supplementation.
Statistical Package for Social Sciences (SPSS) version 23.0 (SPSS, Inc., Chicago, IL, USA) was used for data analysis, and variables were expressed as mean ± standard deviation. Independent Student's t-test was used to compare mean differences between two independent variables, paired t-test was used to compare mean differences between two related variables, and the level of statistical significance was set at P < 0.05.
| Results|| |
As shown in [Table 1], the mean serum levels of adiponectin, progesterone, and SHBG were significantly lower whereas FSH, LH, testosterone, prolactin, and estradiol were significantly higher in women with PCOS when compared with the control (P < 0.05).
|Table 1: Serum levels of adiponectin and fertility hormones in women with polycystic ovarian syndrome and control|
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Before supplementation, there were no significant differences in the mean serum levels of adiponectin, FSH, LH, testosterone, prolactin, estradiol, progesterone, estradiol, and SHBG in PCOS women on omega-3 when compared with those on placebo (P > 0.05), as shown in [Table 2].
|Table 2: Serum levels of adiponectin and fertility hormones in women with polycystic ovarian syndrome on omega-3 and placebo before supplementation|
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As shown in [Table 3], the mean serum levels of adiponectin and progesterone increased significantly while FSH, LH, testosterone, prolactin, and estradiol reduced significantly in PCOS women on omega-3 supplements when compared with those on placebo after 12 weeks (P < 0.05). The mean serum SHBG level however did not differ significantly in PCOS women on omega 3 supplements when compared with those on placebo after 12 weeks (P = 0.859).
|Table 3: Serum levels of adiponectin and fertility hormones in women with polycystic ovarian syndrome on omega-3 and placebo after 12 weeks of supplementation|
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As shown in [Table 4], the mean serum adiponectin and progesterone levels increased significantly while FSH, LH, testosterone, prolactin, and estradiol levels decreased significantly after 12 weeks of omega 3 supplementation in women with PCOS when compared with the levels at baseline (P < 0.05). There was however no significant difference in the mean serum SHBG level in women with PCOS after 12 weeks of supplementation compared with the level at baseline (P = 0.116).
|Table 4: Serum levels of adiponectin and fertility hormones in women with polycystic ovarian syndrome before and after 12 weeks of omega-3 supplementation|
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There were no significant differences in the mean serum levels of adiponectin, FSH, LH, testosterone, prolactin, estradiol, progesterone, estradiol, and SHBG before and after 12 weeks of placebo supplementation in women with PCOS (P > 0.05), as shown in [Table 5].
|Table 5: Serum levels of adiponectin and fertility hormones in women with polycystic ovarian syndrome before and after 12 weeks of placebo supplementation|
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| Discussion|| |
The present study evaluated the effect of omega-3 supplementation in women with PCOS with respect to serum adiponectin and fertility hormone levels.
The lower serum adiponectin level observed in women with PCOS is in line with the earlier studies done by Onyegbule et al. and Hamed which reported significantly lower serum adiponectin levels in women with PCOS and lower baseline adiponectin and AdipoR1 in PCOS group compared to healthy women, respectively.
The hormonal profile in women with PCOS were also altered, and this was evident in the higher levels of FSH, LH, testosterone, prolactin, and estradiol as well as lower levels of progesterone and SHBG. These alterations may be attributed to aberrations in pituitary gonadotropin secretion, excessive activity of 17α-hydroxylase (the enzyme that controls conversion of 17-hydroxy-progesterone into androstenedione) or reduced synthesis of insulin-like growth factor binding protein 1. The alterations in the hormone levels in PCOS women as observed in this study may have negative implications for female fertility.
The higher serum level of testosterone observed in women with PCOS points to a prevailing hyperandrogenism in these women, and this may be associated with impaired feedback in the hypothalamic-pituitary-ovarian axis (HPO), hypersecretion of LH, premature granulosa cell luteinization, or premature arrest of activated primary follicles. The disruption of normal ovarian or adrenal function results in the production of excess androgens, and consequently, impaired folliculogenesis. This is in agreement with the reports of Sathyapalan et al. and Demi et al. who also observed significantly higher testosterone level in women with PCOS.
Disruption in the neuroendocrine system results to an imbalance in the HPO axis, triggering overproduction of gonadotropins (LH and FSH) as observed in the present study. This corresponds with the reports of Gatea et al. and Arshad et al. who also observed significant increase in mean serum FSH and LH levels in PCOS participants compared to the control group. Fathi and Demi et al. however observed significant increase in LH with no significant alterations in FSH level in PCOS women when compared to control.
The elevated level of serum estradiol in women with PCOS as observed in the present study may have resulted from the increased androgen concentration producing an imbalance in estrogen metabolism (as excess androgen is converted into estrogens in the fatty tissue). This is in line with the reports of Bartolone et al. and Khmil et al., and contradicts with those of Arshad et al. and Fathi who reported a reduced estradiol level in PCOS women. Demi et al. however did not observe any significant differences in the mean serum estradiol level in women with PCOS compared to the control group.
The higher serum prolactin level observed in women with PCOS could either be associated with the effect of hyperestrogenemia or the elevated LH levels in women with PCOS which results to a secondary decrease in dopaminergic tone, thus increasing prolactin levels.
Serum progesterone level on the other hand was significantly lower in women with PCOS compared to the control group, and this low level may be associated with luteal phase deficiency in women with PCOS, this agrees with the studies done by Arshad et al. and Gatea et al. who also reported low progesterone levels in women with PCOS. Demi et al., in their study, however, observed no significant difference in progesterone level in women with PCOS compared to the control group.
The lower level of serum SHBG (a transport carrier that binds estrogen and androgens and regulates their biological activities) in women with PCOS as observed in the present study may serve as an indicator of hyperandrogenism in women with PCOS. This finding corresponds with those of Ezzat et al. and Li et al. who also reported lower level of SHBG in women with PCOS.
In view of the altered levels of adiponectin and hormonal profile in women with PCOS which increases the risk of infertility, an intervention study using omega-3 capsules was undertaken to explore its possible ameliorating potentials on the altered biochemical profile observed in these women.
In this study, omega-3 increased the serum adiponectin level whereas placebo had no significant effect after 12 weeks of supplementation in women with PCOS. The increase in adiponectin level may be attributed to the stimulation of Adipoq (adiponectin gene) in adipose tissue by omega-3, possibly by acting as ligands of peroxisome proliferator-activated receptor γ which is the transcriptional regulator interacting with Adipoq promoter. This finding is in accordance with the studies done by Tosatti et al. and Yang et al. but contrary to those of Tsitouras et al. and Kratz et al.
The present study similarly showed that omega-3 fatty acid supplementation for 12 weeks had significant effect in improving the altered hormonal profile which was evident in the reduction in the serum levels of testosterone, FSH, LH, prolactin, estradiol and estrogen as well as increased progesterone level. SHBG level however remained unchanged.
The reduction in serum testosterone level observed in this study after 12 weeks of omega-3 supplementation may be linked to the reported anti-androgenic effect of omega-3 PUFA, and may therefore be useful as an adjuvant in hyperandrogenism conditions including PCOS. This decrease may as well be associated with the effect of omega-3 fatty acid on the gonadotropins. This finding corresponds with those of Nadjarzadeh et al. who reported a decrease in testosterone concentration after 8 weeks of supplementation with omega-3 PUFAs. Similar findings were as well reported by Forouhi et al., Hager et al., and Komal et al. after different periods of omega-3 supplementation.
The reduction in FSH, LH, testosterone, prolactin, and estradiol levels as well as increase in progesterone level in the present study may be indicative of the role of omega-3 in improving the levels of these hormones in women with PCOS. Komal et al. and Pareek and Boolchandani similarly reported significant reduction in LH level in PCOS women after omega-3 fatty acid supplementation. On the contrary, Maarouf et al., Hager et al., and Pareek and Boolchandani observed no significant alterations in LH, FSH or testosterone levels or in all the three hormones, and this may be due to the differences in study duration and/or doses of omega-3-fatty acid supplement used in these studies.
Nadjarzadeh et al. showed that omega-3 intake for 8 weeks did not significantly affect serum prolactin, progesterone and estrogen concentrations. Hajishafiee et al. likewise reported that the mean SHBG level did not differ significantly in PCOS women who took omega-3 supplements compared to those that were on Placebo.
| Conclusion|| |
Omega-3 supplements have shown to be effective in improving the levels of serum adiponectin and fertility hormones in women with PCOS.
This study highlights the beneficial effect of omega-3 PUFA in improving certain biochemical and hormonal alterations in women with PCOS. Omega-3 PUFA supplements may therefore be recommended and used as part of the regimen in the management of patients with PCOS.
This study will be useful to health workers and caregivers in the management of certain adverse health outcomes in women with PCOS, thereby improving the quality of life.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]