Table 3.

Studies examining PRL in relation to maternal metabolism during lactation and postpartum – 10 studies.

Author and year	Design	Participants and sample size	Methodology	PRL postpartum timepoints	Metabolic parameters analysed in relation to PRL	Results	Authors’ conclusions	Risk of bias rating
Erickson et al, 2020 (33)	Cross sectional	n=32 lactating mothers (all BMI <40, no PGDM or GDM)	On day 4-5 postpartum: PRL sampled at feed onset, and then at 20min	Day 4-5 postpartum	Maternal BMI at delivery	Maternal BMI at delivery NS related to baseline PRL at 4-5 days postpartum. Maternal BMI at delivery also NS related to PRL increase across feed.	No relationship between maternal BMI at delivery and either baseline PRL, or PRL increment across feed; at 4-5 days postpartum.	Moderate
Harreiter et al, 2019 (34)	Cross sectional	n=106 n=51 had had GDM; n=11 had ongoing IGT 62 were lactating	One-off PRL measurement at time of OGTT at 3-5 months postpartum	3-5 months postpartum	Maternal pre-preg BMI Postpartum waist circ and hip circ, triglycerides (3-5mo PP), HDL, fasting glucose Total chol (3-5mo PP), LDL Fasting insulin, fasting C-peptide, HOMA-IR, pre- and post-hepatic beta-cell fx Post glucose load: OGIS, AUC insulin, IGT, GDM Insulinogenic index, Stumvoll 1st and 2nd phase, disposition index, AUC ins/gluc AUC glucose	PRL neg assoc, -0.205, sig. PRL NS assoc PRL pos assoc, sig. PRL neg assoc, sig. PRL NS assoc. PRL neg assoc, sig. PRL pos assoc, sig.	Higher PRL levels assoc with lower pre-preg BMI and lower postpartum fasting insulin (univariate analyses, listed). After multivariate analysis, pre-hepatic beta-cell function and Stumvoll 1st phase insulin secretion index (but not BMI) independently and neg assoc with PRL levels. Conclusion was that beta-cell function lower in lactating than non-lactating women (independent of BMI) and is inv assoc with PRL. Both lean and obese lactating mothers have lower IR. Authors suggest that good beta-cell plasticity (allowing beta-cell function to fall from high insulin production during preg to low production postpartum) may enable PRL to rise with permissive effect on lactation.	Moderate
Montelongo et al, 1992 (23)	Longitudinal observational	n=9 early GDM n=12 healthy controls	PRL sampled at 2-4 weeks postpartum (during lactation) and again after cessation of lactation	2-4 weeks postpartum, during lactation Post-lactation	Diabetes category	NS diff between mean ( ± SEM) PRL (ng/mL) either during lactation or post-lactation between GDM and controls At 2-4 wk postpartum (lactation): GDM 41.22 ± 10.71 vs. controls 62.54 ± 13.16; NS After cessation of lactation: GDM 7.33 ± 1.85 vs. controls 6.12 ± 0.83; NS	NS difference in PRL between GDM and control women in the postpartum period; either during lactation or after cessation thereof.	Moderate
Nurek et al, 2021 (35)	Cross sectional	n= 20 healthy exclusively BF at 3mo postpartum n=17 healthy partially BF at 6mo postpartum n=17 healthy FF at 3-6mo postpartum	One-off fasting PRL sample	3-6 months postpartum	In lactating women only: Maternal BMI Maternal body weight Fasting insulin	NS PRL pos assoc, 0.281, sig NS	Lactation overall assoc with high basal PRL and low basal insulin levels (compared with non-lactating group). Within lactating group, PRL NS rel to insulin or maternal BMI. Pos assoc to absolute maternal weight found, but likely confounded by different measurement timing between partial and exclusively breastfeeding groups.	Moderate
Ozisik et al, 2019 (36)	Cross sectional	n=12 lactating (2 had had GDM), n=11 non-lactating (none GDM)	One-off PRL measurement, and meal tolerance test	Postpartum period, not further defined	Across whole cohort: Hba1c  2 hour C-peptide HOMA-IR  HOMA-IS  AUC-insulin AUC-glucose  In both lactating and non-lactating women: BMI Waist circumference Fasting glucose Fasting insulin Fasting C-peptide 1, 2, 3, 4, 5-hour glucose 1, 2, 3, 4, 5-hour insulin 1, 2, 3, 4, 5-hour C-peptide	PRL neg assoc, r= -0.564, sig. PRL neg assoc, r= -0.539, sig. PRL NS assoc PRL NS assoc PRL NS assoc PRL NS assoc PRL NS assoc PRL NS assoc PRL NS assoc PRL NS assoc PRL NS assoc PRL NS assoc PRL NS assoc PRL NS assoc	PRL in postpartum women (lactating and non-lactating) inversely associated with HbA1c and C-peptide. Authors state this supports “protective” effect of PRL in postpartum period and may reflect improved insulin sensitivity.	High
Ramos-Roman et al, 2020 (37)	Cross sectional	n=12 lactating (83% exclusively breastfeeding), 8 had had GDM n=6 non-lactating (formula-feeding), 3 had had GDM	Extensive clinical studies, including hyperinsulinaemic euglycaemic clamp, at 5-8 weeks postpartum	5-8 weeks postpartum	For lactating women, during the clamp: Ra free fatty acid suppression % Free fatty acid suppression % Intrahepatic Tg% Plasma Tg	PRL neg assoc, r= -0.52, sig. PRL NS assoc, PRL neg assoc, r= -0.62, sig. PRL neg assoc, r = -0.57, sig.	Both lactating and non-lactating women had low insulin. Fasted, lactating women had 2.6x higher basal EGP and 2.3x rates of lipolysis compared with non-lactating. When hyperinsulinaemic euglycaemic clamp applied (mimicking fed state), both groups suppressed lipolysis and EGP, but lactating women needed 36% less insulin to do so, suggesting postpartum insulin sensitivity may be further augmented by lactation. In lactating group, higher PRL was related to better insulin-mediated suppression of lipolysis, and lower intra-hepatic and circulating Tg.	Low
Rasmussen et al, 2014 (38)	Longitudinal observational	n=17 overweight/obese (BMI >26 kg/m2) n=23 lean controls	PRL measured at baseline, and 30min into breastfeeding: at 48h postpartum and then 7 days postpartum.	48 hours postpartum 7 days postpartum	Maternal pre-preg BMI category	Mean PRL response to suckling, ΔPRL (ng/mL) sig lower in overweight/obese women than lean control women at 48h, but not 7 days. At 48h: overweight/obese ΔPRL = -10.3 ± 28.3 vs. lean 26 ± 61.5; sig. At 7 days: overweight/obese ΔPRL = 57.1 ± 60.2 vs. lean 80.9 ± 67.6, NS	Women who were overweight or obese pre-conception had lower PRL response to suckling than normal-weight women at 48h, but not 7 days, postpartum. Maternal overweight/obesity was sig independent predictor of lower PRL response to suckling at both 48h and 7 days postpartum; which may explain higher rates of breastfeeding cessation in this group.	Moderate
Ren et al, 2022 (31)	Longitudinal observational	n=30 overweight/obese (pre-preg BMI >24 kg/m2, Chinese pop) n=33 lean controls (pre-preg BMI 18.5-23.9 kg/m2)	PRL sampled at 37 weeks of preg, and again at 48h postpartum	37 weeks preg 48 hours postpartum	Maternal pre-preg BMI category	Baseline PRL in ng/mL sig lower in overweight/obese women than lean control women at both 37 weeks of preg (see Table 2 ) and 48h postpartum. At 48h postpartum overweight/obese 281.79 ± 87.61 vs. lean 392.96 ± 104.54, sig.	Women with pre-preg overweight/obesity had lower basal PRL levels at both 37 weeks preg and 48h postpartum than normal-weight peers. They also had significantly delayed onset of lactogenesis. Factors emerging as likely sig contributors to the lactogenesis delay (and poss also lower PRL levels) in the overweight/obese group were (a) higher late-preg leptin levels and (b) a slower fall in estrogen following delivery.	Low
Retnakaran et al, 2016 (39)	Longitudinal observational	n=301 NGT n=60 pre-diabetes n=6 DM (based on OGTT at 3 months postpartum)	PRL sampled at time of OGTT in late second trimester of preg, but then analysed in relation to postpartum metabolic status	Late second trimester of preg (but related to postpartum metabolic status)	Maternal diabetes category at 3 mo postpartum Glycaemic markers at 3mo postpartum: Log Matsuda index Log HOMA-IR Log ISSI-2 Log IGI/HOMA-IR Fasting glucose AUC glucose Risk of pre-diabetes or DM at 3mo postpartum	Median (IQR) PRL in ng/mL had been sig higher in late 2nd trimester in those with NGT than those with persistent dysglycaemia at 3 mo postpartum: NGT = 93.4 (72.9-121.9) vs. pre-diabetes 82.7 (60.4-97.5) vs. DM 79.2 (52.2-100.4); sig (adjusted for key postpartum variables) PRL NS assoc PRL NS assoc PRL pos assoc, 0.0016, sig. PRL pos assoc, 0.0031, sig. PRL NS assoc PRL neg assoc, -0.0111, sig. OR of pre DM or DM at 3mo PP for each SD increase of PRL in late preg: OR = 0.50 (0.35, 0.72), sig.(after adjusting for key postpartum variables)	PRL in late preg had been sig higher in those with NGT at 3mo postpartum than in those with postpartum pre-diabetes or DM. Higher late preg PRL independently predicted higher beta-cell function at 3 mo.  PRL in late preg was independent predictor of risk of pre-DM or DM at 3mo PP (higher late preg PRL predicted lower dysglycaemia risk).   Authors suggest that serum PRL in preg may provide novel insight into postpartum DM risk in young women, and suggest this might relate to known role of PRL in beta-cell mass expansion (here extending from preg into postpartum).	Moderate
Skouby et al, 1986 (28)	Longitudinal observational	n=15 GDM, n=15 non-GDM all lactating at time of postpartum follow-up	PRL sampling and OGTT in late preg (33-38 weeks, see Table 1 ), repeated during lactation at 4-8 weeks postpartum	4-8 weeks postpartum	GDM status Change in OGTT glucose AUC between late preg and postpartum	Mean ( ± SEM) PRL during lactation NS different in GDM vs control women: GDM = 54 ± 9 vs controls 46 ± 10 ng/mL, NS. No relationship to change in PRL between late preg and postpartum (in either GDM or controls)	NS difference in mean PRL between GDM and non-GDM women either in later preg or at 4-8 weeks postpartum, during lactation. No assoc found between PRL change (preg to postpartum) and change in AUC glucose (preg to postpartum). PRL did not change during OGTT (either in preg or postpartum).	Moderate

BMI, body mass index; PGDM, pre-gestational diabetes mellitus; GDM, gestational diabetes mellitus; DM, diabetes mellitus; IGT, impaired glucose tolerance; NGT, normal glucose tolerance; OGTT, oral glucose tolerance test; PRL, prolactin; BF, breastfeeding; FF, formula feeding; HDL, high-density lipoprotein; LDL, low-density lipoprotein; HOMA-IR, Homeostatic Model Assessment for Insulin Resistance; AUC, area under the curve; NS, non significant; IR, insulin resistance; OGIS, oral glucose insulin sensitivity; Tg, triglycerides; OR, odds ratio; ISSI, insulin-secretion sensitivity index; IGI, insulinogenic index; R_a, rate of appearance; EGP, endogenous glucose production. Data are presented as mean ± SD unless otherwise specified in the table.