Table 6 Effects of tobacco on ovarian function

Matikainen et al., 2001 [63]

Adult mouse exposure to a single intraperitoneal injection of 9,10-dimethylbenz[a]anthracene (DMBA) 50 mg/kg, a typical PAH

Activation of the aromatic hydrocarbon receptor (Ahr) driving Bax expression in oocytes, a pro-apoptosis factor

Jurisicova et al., 2007 [78]

Exposure of mice to 2 PAHs (DMBA and BaP) 3 weeks before gestation and during lactation

⇘ by one third of the ovarian follicle pool in F1 compared to unexposed offspring

Paixão et al., 2012 [79]

Exposure of 10 mice to cigarette smoke 8 h/day, 7 days/week for 15 days. Euthanized at the end of exposure or 30 days after.

Alteration in follicular growth even after discontinuing the exposure.

⇘ Number of granulosa cells in the exposed group

Kilic et al., 2012 [76]

Prospective randomized study, 25 pregnant rats exposed or unexposed to cigarette smoke.

significant ⇗ in DNA anomalies and the apoptotic index in the ovaries of exposed group

⇘ offspring ovarian reserve

Gannon et al., 2012 [77]

Mice exposed to tobacco smoke 5 day/week, for 4, 8, 9 or 17 weeks.

⇘ ovary weight and number of primordial follicles.

⇗ oxidative stress. Bcl-2 expression ⇘ but apoptosis was not induced

Sobinoff et al., 2013 [65]

Nasal exposure of mice to cigarette smoke. Ovarian toxicity analysis

⇗ Depletion of primordial and antral follicular stock via, mechanisms of apoptosis and oxidative stress

Lim et al., 2013 [89]

Mouse exposed by gavage to B[a]P at 0.2 or 10 mg/kg/d from the 7th to 16th gestational day. Effect of polymorphism of glutamate cysteine ligase

Prenatal exposure to BaP induced POI. Deletion of glutamate cysteine ligase increased the sensitivity of these ovarian effects

Camlin et al., 2016 [82]

Nasal exposure of pregnant mice to cigarette smoke for 12 weeks. Analysis of F1 ovary and oocyte quality

Abnormal proliferation of neonatal somatic cells,

⇗ apoptosis, ⇘ follicles at birth and at the adult age.

⇗ oxidative stress

Progetto Menopausa Italia Study Group, 2003 [74]

Cross-sectional study between 1997 and 1999.

Inclusion of patients between ages 45 to 75 making a 1st consultation in a specialized center for menopause in Italy

No significant association between the risk of POI and smoking

Chang et al., 2007 [72]

Study of risk factors in 137 menopausal patients < 40 years, 281 between 40 and 4 years, and 1318 between 45 and 60 years

Smoking ⇗ the idiopathic risk of POI: OR = 1.82 [1.03–3.23]

Kinney et al., 2007 [110]

Effect of cigarette smoking on antral follicle count and FSH in 188 patients aged 22 to 49 years

Chronic cigarette smoking is associated with higher rates of FSH β = 0.21, 95% CI = 0.04, 0.39, but there is no significant difference on the AFC

Strohsnitter et al., 2008 [84]

Epidemiological study on 4025 women. Association between prenatal exposure to cigarette smoking and age at menopause

An association between prenatal exposure and age at menopause for patients who have never smoked (HR = 1.38, 95% CI: 1.10, 1.74). Not found in patients who smoke (HR = 1.03, 95% CI: 0.81, 1.31)

Fleming et al., 2008 [70]

Epidemiological study on 7596 women. Cotinine and FSH levels in the blood

Average age at menopause = 47.17 years for smokers compared to 48.59 years for non-smokers.

Freour et al., 2008 [81]

Analysis of 111 patients treated for infertility

Significant ⇘ of AMH levels in patients who smoke 3.06 +/− 1.68 mg/L, compared to 3.86 +/− 1.92

Lutterodt et al., 2009 [87]

Ovary analysis of 29 fetuses in the 1st trimester. Ovary analysis, compared to maternal cigarette smoking exposure

⇘ number of somatic cells (P ≤ 0.01). Number of oogonia not associated with prenatal exposure to maternal cigarette smoking (P ≤ 0.09).

Ernst et al., 2012 [86]

Prospective study on 965 pregnant women at 30 weeks amenorrhea. Evaluation of maternal cigarette smoking and study in 2008 on the fertility of their daughter (n = 438)

No significant association between in utero cigarette smoking exposure and the number of follicles

(Yasui et al., 2012)

Transversal study of a cohort of 24,152 Japanese nurses, research on factors associated with POI

Cigarette smoking is associated with an earlier age at menopause

Fraser et al., 2013 [83]

Analysis of a cohort of 1399 adolescents between 1991 and 2008. Study on AMH levels depending on parental exposure to cigarette smoking

Paternal, and not maternal, cigarette smoking before and during pregnancy is associated with a decrease in AMH levels.

Caserta et al., 2013 [80]

Analysis of the antral follicle count and FSH levels in 296 women, including 102 smokers

⇘ Antral follicle count and ⇗ FSH in cigarette smokers correlated to the number of pack- years.

Fowler et al., 2014 [85]

Analysis of 105 fetuses resulting from elective terminations in the 2nd trimester, 56 exposed, 49 unexposed.

Dysregulation of fetal ovarian signaling pathways

Butts et al., 2014 [88]

Survival analysis for a cohort of 410 patients. Nucleotide polymorphism study

Risk of early menopause in cigarette smokers depends on genetic polymorphism.

Tawfik et al., 2015 [71]

Cohort study of 1001 women aged 39 to 49 years. Evaluation of the association between exposure to cigarette smoke throughout the lifetime (prenatal, childhood, adulthood) and menopause status

Prenatal exposure and current cigarette smoking: 3 times more risk of early menopause (3.4; 95% CI, 1.1–10.3). Long-term exposure (>26 years) is associated to the age at menopause.

Peck et al., 2016 [73]

Analysis of primordial follicle stock in 133 patients having underwent hysterectomy for a benign pathology.

No association between follicle count and cigarette smoking

Sun et al., 2012 [66]

Analysis of 11 studies

Effect of cigarette smoking on age at menopause

Dichotomous studies: OR = 0.67 (CI 95%, 0.61 to 0.73, P <0.01). Continuous studies: OR = −0.90 (CI 95%, −1.58 to −0.21, P <0.01)

Cigarette smoking = independent factor in early age at menopause