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Conflict of Interest: None
Declaration: None
Acknowledgment: None
To the editor,
We read with keen interest the article by Johanna Molin et al.
“Gestational weight gain, appetite regulating hormones, and metformin
treatment in polycystic ovary syndrome: A longitudinal, placebo-
controlled study”.1 It highlights the effects of
appetite regulating hormones such as leptin, ghrelin and
allopregnanolone on gestational weight gain (GWG) in pregnant women with
Polycystic Ovary Syndrome (PCOS) and influence of metformin on these
hormones. We concur with the findings that Metformin reduces the risk
for excessive GWG and improves physiological leptin resistance in
pregnant women with PCOS. However, a few points seem to us worth
mentioning based on our experience that could boost the overall the
quality of overall article.
In the original article the authors mainly emphasized on the effects of
Metformin on GWG and maternal appetite regulating hormones but did not
mention the possible effects of Metformin on fetal hormones due to
intrauterine metformin exposure, Sex Hormone Binding Globulin (SHBG), a
β-globulin protein possessing high affinity binding for 17 beta-hydroxy
steroid hormones such as testosterone and estradiol and its synthesis in
liver is inhibited by Insulin. SHBG was elevated in the umbilical vein
in newborn babies exposed to metformin in utero this would indicate that
newborns of PCOS mothers are less insulin resistant if exposed to
metformin in utero.2 Furthermore, leptin in addition
to being a key regulator of endocrine system has pro-inflammatory
properties and it up regulates the secretion of inflammatory cytokines
like IL-6, IL-12 and TNF-α. Serum leptin is elevated in many chronic
inflammatory and autoimmune conditions including inflammatory bowel
disease (IBD), endometriosis, type 1 diabetes mellitus, nephritis,
nonalcoholic steatohepatitis (NASH), chronic obstructive pulmonary
disease (COPD) , Bechet’s disease and Grave’s disease and rheumatoid
arthritis.3 This suggests that pregnant women with
chronic inflammatory diseases could generate false positive result of
increased free leptin levels.
Moreover, there is substantial evidence that Orlistat is as efficacious
as metformin in reducing weight and attains similar ovulation rates in
obese PCOS patients. However, Obese PCOS patients treated with orlistat
showed significant improvements in lipid profile including LDL,
Triglycerides, and total cholesterol at the end of 3 months of pregnancy
and have minimal side‑effects and is better tolerated compared with
metformin.4
In conclusion, the exclusion criteria should include chronic
inflammatory and auto immune diseases to exclude false positive results,
known alcohol abuse as simultaneous consumption of alcohol and metformin
could result in lactic acidosis, treatment with oral glucocorticoids or
use of drugs known to interfere with pharmacokinetics of metformin.
Moreover, the study population should also evaluate black and white
ethnicities separately as Hispanic women with PCOS demonstrate severe
phenotype in terms of hyperandrogenism and metabolism than non-Hispanic
women. The author should also consider other drug regimens such as
orlistat which is as efficacious as metformin with better benefits and
lesser side effects.
REFERENCES:
- Molin, J., Vanky, E., Løvvik, T. S., Dehlin, E., & Bixo, M. (2022).
Gestational weight gain, appetite regulating hormones, and metformin
treatment in polycystic ovary syndrome: A longitudinal,
placebo-controlled study. BJOG : an international journal of
obstetrics and gynaecology , 129 (7), 1112–1121.
https://doi.org/10.1111/1471-0528.17042
- Carlsen, S. M., & Vanky, E. (2010). Metformin influence on hormone
levels at birth, in PCOS mothers and their newborns. Human
reproduction (Oxford, England) , 25 (3), 786–790.
https://doi.org/10.1093/humrep/dep444
- Iikuni, N., Lam, Q. L., Lu, L., Matarese, G., & La Cava, A. (2008).
Leptin and Inflammation. Current immunology
reviews , 4 (2), 70–79.
https://doi.org/10.2174/157339508784325046
- Kumar, P., & Arora, S. (2014). Orlistat in polycystic ovarian
syndrome reduces weight with improvement in lipid profile and
pregnancy rates. Journal of human reproductive
sciences , 7 (4), 255–261.
https://doi.org/10.4103/0974-1208.147492