Lean Women on Metformin and Oral Contraceptives for Polycystic Ovary Syndrome Demonstrate a Dehydrated Osteosarcopenic Phenotype: A Pilot Study

Abstract

Scarce data exist on the body composition of lean women with polycystic ovary syndrome (PCOS) on treatment with metformin and oral contraceptives (OCs). Thirty-four lean (body mass index 18.5–24.9 kg/m2) women (17 with PCOS on metformin and OCs treatment for six months and 17 controls) aged 18–40 years were assessed for body composition parameters (fat, muscle, glycogen, protein masses, bone masses, and body water compartments) and phase angles. PCOS patients demonstrated lower muscle, glycogen and protein masses (U = 60, p = 0.003), along with a lower bone mineral content and mass (U = 78, p = 0.021; U = 74, p = 0.014) than their healthy counterparts, while total and abdominal fat masses were similar between the two groups. PCOS patients also exhibited increased extracellular body water (U = 10, p < 0.001) and decreased intracellular water, compatible with low-grade inflammation and cellular dehydration. Key differences in body composition between women with PCOS and controls demonstrated an osteosarcopenic body composition phenotype in PCOS patients. A confirmation of these findings in larger studies may render osteosarcopenia management a targeted adjunct therapy in women with PCOS.

Improvement Effect of Metformin on Female and Male Reproduction in Endocrine Pathologies and Its Mechanisms

“…In PCOS patients, the efficiency of MF therapy is increased when MF is used with oral estrogen-progestin contraceptives, both acting similar, by suppressing ovarian androgen overproduction and normalizing menstrual cycle, most noticeably in obese PCOS women [ 152 , 153 ]. On a contrary, when the same combined treatment (MF and oral contraceptives) is used for PCOS women with normal or reduced body weight, it results in a decrease in their muscles mass, leads to the water retention and the formation of an “osteosarcopenic” phenotype [ 154 ]. Two main reasons are behind the decrease in the muscles mass during combined therapy.…”

“…In this regard, it should be noted that MF treatment of T2DM patients leads to an increase in the blood level of fibroblast growth factor 21 (FGF21), which is one of the specific markers of muscles damage and degeneration [ 157 ]. Thus, it is highly recommended to take into account the proportion of the muscle tissue and body mass index in PCOS women, as well as the severity of HA when considering the option of using the combined therapy of MF and oral contraceptives [ 154 ].…”

Circulating levels of Meteorin-like protein in polycystic ovary syndrome: A case-control study

“…instance, Stefanaki et al showed that lean PCOS females (BMI 18.5-24.9 kg/m 2 ) exhibited an osteosarcopenic phenotype, characterized by low muscle mass and bone mineral density, but normal total and subcutaneous fat mass [45]. A recent study by Du et al found that serum Metrnl levels negatively correlated with visceral adiposity (exceeding 100 cm 2 ) in diabetic patients (OR = 0.846, 95% CI [0.745-0.961], P = 0.01) [46].…”

Obesity, but not hyperandrogenism or insulin resistance, predicts skeletal muscle mass in reproductive‐aged women with polycystic ovary syndrome: A systematic review and meta‐analysis of 45 observational studies

“…27,28 The likelihood of muscle alterations in PCOS is also supported by evidence of decreased insulin-mediated glucose uptake in the major insulin target tissues (myocytes and adipocytes). 29 Moreover, carotid intima-media thickness 30 secondary to vascular dysfunction, 31 and muscle protein degradation secondary to an aggravated muscle sympathetic nerve activity 28,32,33 in PCOS could adversely affect muscle mass in this clinical population.…”

“…36,37 Current evidence has yielded conflicting results regarding muscular mass status in women with PCOS versus controls with clinically normal ovarian function. Some studies have reported decreased total [38][39][40] and/or limb (arms and legs) 27,33,38,[41][42][43] lean tissue mass in women with PCOS versus controls. Other studies showed no differences in total [44][45][46] or limb [47][48][49][50] lean tissue mass, or muscle strength [51][52][53] between groups.…”