Smoke, alcohol and drug addiction and female fertility

Abstract

Background: Considerable interest has been gathered on the relevant impact of preventable factors, including incorrect lifestyle and unhealthy habits, on female fertility. Smoking, alcohol and addictive drugs consumption represent a major concern, given the broad range of diseases which might be favored or exacerbated by these dependable attitudes. Despite the well-characterized effects of prenatal exposure on pregnancy outcomes and fetus health, a substantial proportion of women of reproductive age is still concerned with these habits. At present, the impact of smoke, alcohol and addictive drugs on women fertility, and, particularly, the specific targets and underlying mechanisms, are still poorly understood or debated, mainly due to the scarcity of well-designed studies, and to numerous biases.

Objective: The current review will provide a comprehensive overview of clinical and experimental studies in humans and animals addressing the impact of smoke, alcohol and addictive drugs on female fertility, by also embracing effects on ovary, oviduct, and uterus, with particular reference to primary endpoints such as ovarian reserve, steroidogenesis, ovulation and menstrual cycle, oviduct function and uterus receptivity and implantation. A brief focus on polycystic ovary syndrome and endometriosis will be also included.

Methods: A Pubmed literature search was performed with selected keywords; articles were individually retrieved by each author. No limitation was set for publication date. Articles in languages other than English were excluded. Additional articles were retrieved from references list of selected manuscripts.

Results and conclusions: Currently, the most consistent evidences of a detrimental effect of smoke, alcohol and addictive drugs on specific domains of the female reproductive function are provided by experimental studies in animals. Overall, clinical studies suggest that smoking is associated to decreased fertility, although causal inference should be further demonstrated. Studies addressing the effect of alcohol consumption on female fertility provide conflicting results, although the majority reported lack of a correlation. Extremely scarce studies investigated the effects of addictive drugs on female fertility, and the specific actions of selected drugs have been difficult to address, due to multidrug consumption.

Keywords: Alcohol; Drug; Endometriosis; Female Fertility; Ovary; Oviduct; PCOS; Reproduction; Smoke; Uterus.

Fig. 1

Graphical summary of the main effects of smoking on the reproductive function in women. Smoking affects nearly all domains of the female reproductive function. Smoking is associated to early menopause and reduced levels of ovarian reserve markers, mediated by an impairment of antral follicle development and growth, due to supportive granulosa cells-directed oxidative stress and DNA damage, resulting in cytotoxicity and production of poor quality oocytes. Smoking is associated to lower estrogens and progesterone and higher androgens levels, effects mediated by both ovarian and extra-ovarian actions, including: increased levels of sex hormone binding globulin (SHBG); increased hepatic production of estrogens metabolites with minimal estrogenic activity by pushing the estrogens 2-hydrohylation pathway; inhibition of aromatase enzyme; increased expression of ovarian CYP1B1 enzyme; increased levels of adrenocorticotropic hormone (ACTH); inhibition of adrenal 21-hydrohylase enzyme. Smoking is associated to an increased risk of ectopic pregnancy, mediated by affected oviductal smooth muscle contractility, to delayed implantation, mediated by reduced endometrium receptivity and cytotrophoblast proliferation, migration and invasion, and to an increased risk of oligomenorrhea, dysmenorrhea and menstrual symptoms, although apparently not determined by ovulatory dysfunction

Fig. 2

Graphical summary of the main effects of alcohol consumption on the reproductive function in women. Alcohol consumption is associated to higher estrogens and lower progesterone levels, effects mediated by both ovarian and extra-ovarian actions, including: decreased hepatic oxidation of estradiol to estrone; increase of aromatase activity; decreased hepatic conversion of pregnenolone to progesterone; reduced cholesterol uptake; decreased expression of luteinizing hormone (LH) human chorionic gonadotropin (hCG) receptors expression in granulosa cells. Alcohol consumption is associated to reduced oviductal smooth muscle cells contractility, although apparently not resulting in increased ectopic pregnancy rate, and to reduced cytotrophoblast proliferation, and increased cytotrophoblast apoptosis. Alcohol consumption is associated to irregular menstrual cycles and ovulatory dysfunction