Let's now take a look at how alcohol affects males and females separately. Alcohol consumption has been associated with several reproductive disorders in women, including irregular menstrual cycles, absence of ovulation, and increased risk of spontaneous miscarriage and early menopause. Compared to women who don't drink alcohol, women who drink are 74% more likely to experience pain, During sexual intercourse, a lack of sexual desire, and disturbances in sexual arousal or orgasm. They are also 45% more likely to experience premenstrual syndrome, also known as PMS. Heavy drinking defined as consuming one or more standard drinks per day further increases the risk of PMS to 79% when compared to never drinking. Alcohol consumption also reduces the ability of women to experience a pregnancy.

Compared to women who never drink, light drinkers have an 11% lower chance of pregnancy and moderate drinkers have a 23% lower chance. Light and moderate drinking were defined here as consuming less than 1 standard drink or more than 1 standard drink per day, respectively. For every 1 extra drink per day, the chance of experiencing a pregnancy dropped by 2%. However, some studies suggest that avoiding alcohol altogether may not be necessary to achieve a pregnancy. In one observational study of Danish women, consuming up to 14 alcoholic drinks per week did not affect fertility, which was only negatively impacted when women consumed more than 14 drinks per week. The type of alcohol consumed didn't seem to matter. Beer or wine were associated with the same odds of fertility among drinkers.

There's also some evidence that consuming alcohol may reduce egg and embryo quality. In a study of 54 women taking part in a program for in vitro fertilization, there was a dose-response relationship between alcohol consumption and embryo quality. The study classified embryo quality as Class A being embryos with the highest reproductive potential, Class B being embryos with slight deviations in reproductive quality, and Class C being embryos with considerable abnormalities. Among the women who reported consuming any alcohol, only 4% of the embryos were classified as Class A, while 87% were Class B and 9% were Class C. Among the women who didn't consume alcohol, 42% of the embryos were Class A, 39% were Class B, And 19% were Class C. In other words, consuming alcohol appears to cause some abnormalities in embryos and downgrade them from Class A to Class B. The dose of alcohol consumed also matters.

In the same group of participants, only 15% of embryos were classified as Class A for women who consumed up to 25 grams of alcohol or an equivalent of just 2 drinks per day. Class A embryos constituted just 4.5% of the embryos for women who consumed more than 2 drinks per day. However, among the women who reported only sporadic alcohol consumption, Class A embryos constituted 44% of the embryos. And for those who reported total abstinence from alcohol, Class A embryos constituted 70% of the embryos. Let's look at these results in another way. More Class B embryos came from women who consumed more than 25 grams of alcohol per day. So 72% were Class B embryos compared to those who consumed alcohol sporadically.

Only 44% of those were Class B embryos and those who abstained from alcohol, only 30% of those were Class B embryos. The conclusion here is that consuming more alcohol leads to more abnormalities in embryos and a decreased reproductive potential. Looking at embryo quality is one thing, but is there any evidence that alcohol leads to worse pregnancy outcomes among women who undergo IVF or intracytoplasmic sperm injection, another assisted reproductive technology? Overall, consuming alcohol does not appear to have a strong association with achieving a pregnancy after IVF or intracytoplasmic sperm injection. However, The dose of alcohol again seems to be important.

There is a negative association between alcohol consumption and the odds of achieving a pregnancy when a woman's weekly alcohol consumption exceeds 84 grams, which is the equivalent of about 6 standard drinks. That amount would be considered moderate drinking for women. If we compare moderate drinking women to women who abstain from alcohol, the chance of achieving a pregnancy after IVF or intracytoplasmic sperm injection drops by about 7%. What's also interesting is that paternal alcohol consumption was also associated with a lower chance of their partner achieving a pregnancy. When the father consumed 6 or more drinks per week, the chance of their partner achieving a live pregnancy fell by 9%.

Alcohol consumption has also been associated with changes in several hormones in premenopausal women. An acute dose of alcohol equal to 0.7 grams per kilogram of body weight increases plasma estradiol levels by 55 to 60%. 66% above baseline levels and consuming a similar dose every day in the morning and evening for 1 week elevates total testosterone levels. Daily consumption of 30 grams of alcohol also causes elevations in plasma levels of DHEAS in the follicular phase, estrone and estradiol in the periovulatory phase, and estrone, estradiol, and estriol in the luteal phase. Now let's talk about male sexual health and fertility.

Light to moderate consumption of 14 or fewer drinks, and even high consumption of 14 or more drinks per week, is associated with a lower risk of erectile dysfunction in males. However, any alcohol consumption does appear to reduce semen quality in males. An analysis of over 40 studies involved more than 23,000 men observed that drinking alcohol reduced semen volume, reduced antioxidant enzymes present in semen, and lowered levels of testosterone, follicle stimulating hormone, and luteinizing hormone. But drinking did not influence sperm density, motility, morphology, or DNA fragmentation. In this study, drinking 1 to 7 alcoholic drinks per week appeared to offer protection against these effects, as no significant changes were observed in semen parameters or sex hormones.

However, having more than 7 drinks per week was associated with lower semen volume, testosterone, and follicle stimulating hormone, as well as higher levels of estrogen and luteinizing hormone compared to non-drinkers. Other studies had confirmed that consuming between 4 and 7 drinks per week may improve fertility compared to drinking 1 to 3 drinks or 8 or more drinks per week, while heavy alcohol consumption of 25 to 40 or more drinks per week leads to drastic reductions in sperm count and normal-looking sperm. Despite some of this evidence I just presented, I really want to emphasize that expecting parents or couples who are hoping to become pregnant should really think about their alcohol use.

There is some good evidence that drinking behavior by the mother and father before conception can really have an impact on the baby's growth and development. This even applies to the time before you know you are pregnant. I'll talk about a few impactful studies here, but note that most of these studies were conducted in rats or mice, unless I specify. In one study, consuming the equivalent of 5 standard drinks around the time of conception caused the offspring to have impaired glucose tolerance and reduced insulin sensitivity when they were 6 months old, which could translate to a higher risk of childhood type 2 diabetes and obesity if these findings extend to humans.

In a similar study, exposure to binge drinking levels of alcohol before conception led to smaller offspring body weight and reduced behavioral and pubertal development, regardless of which parent was exposed to the alcohol. I want to underscore the last point about paternal alcohol consumption also having the ability to influence the health and development of the child, because normally it's only the mother whom we think about. Paternal alcohol intake has been linked to deficits in skull and facial growth and development, reduced organ growth in the heart, lungs, liver, and kidney, and impaired development in brain regions responsible for complex cognitive functions and behavior, several of which are characteristic of fetal alcohol spectrum disorders.

What can you do if you're an expecting parent and trying to reduce these risks? Well, researchers in this field suggest that fathers and probably mothers too, should abstain from alcohol for at least 3 months before trying to get pregnant to make sure that any lingering effects of alcohol on sperm and egg quality and function are minimized. This is longer than the 1 month that has been previously recommended, but I think it's better to be overly cautious and safe than sorry. So fathers are just as responsible as mothers for ensuring that they are engaging in low-risk drinking habits prior to their partner getting pregnant.

These emerging data are, in my opinion, so incredibly important because as you're probably aware, labels on alcohol products typically only caution pregnant women to avoid alcohol. Now, based on good scientific evidence in animal models, these labels should probably include information on expecting mothers and fathers. The ability of a father's behavior to influence their offspring's growth is related to epigenetic changes that I'll discuss shortly. And it really emphasizes that the health of both parents is super important to ensure a healthy, happy child. Now I want to discuss how alcohol affects sex hormones in men, because testosterone is often brought up as something that men are concerned about.

Regarding testosterone, results from some studies in humans and in vitro studies are somewhat mixed. In general, chronic heavy alcohol consumption is associated with lower testosterone levels. While low to moderate alcohol consumption does not appear to reduce testosterone and may even increase testosterone levels somewhat. The main mechanism to explain an increase in testosterone levels with low to moderate intakes of alcohol is an increase in detoxification enzymes in the liver. Metabolizing alcohol requires the enzyme alcohol dehydrogenase and nicotinamide adenine dinucleotide, or NAD+. Using up NAD increases the NADH to NAD ratio, which activates the liver enzyme 17-beta-hydroxysteroid dehydrogenase. When this happens, more of the hormone androstenedione is converted into testosterone.

The main mechanisms by which heavy alcohol consumption reduces testosterone are through its effects on the HPA axis, oxidative stress, and inflammation. Here, I'll briefly focus on the HPA axis, which is the cascade involved in our body's so-called stress response. Consuming alcohol stimulates corticotropin-releasing hormone, or CRH, from the hypothalamus. CRH causes the release of adrenocorticotropic hormone, or ACTH, from the pituitary gland. And finally, ACTH stimulates cortisol release from the adrenal gland. High levels of cortisol, especially chronically high levels, blunt testosterone production and secretion From the testes. As a wrap-up to this discussion on fertility, I want to discuss how alcohol can affect the health of newborns through its epigenetic effects.

I already discussed some of this information when I spoke about how maternal and paternal alcohol consumption can impact fetal health, but it's important enough to underscore and expand upon. What I'm going to talk about is different from maternal alcohol consumption during pregnancy, which is highly cautioned against. There is no safe level of alcohol consumption during pregnancy or even when trying to get pregnant. Fetal alcohol spectrum disorders are entirely preventable if you avoid exposing yourself and the baby to alcohol during these crucial time points. It is well known that drugs, cigarette smoke, dietary micronutrients, and alcohol in utero can have effects on the developing embryo that might manifest during childhood and can even last until adulthood.

But even before conception, when a mother's eggs are maturing, environmental and dietary exposures can still impact characteristics of eggs and the health of the child after birth. During the egg maturation phase, a process called genomic imprinting occurs and impacts literally every cell of the developing child. One study observed that mothers who consumed alcohol at any point were less likely to have children with a genomic imprint at a non-coding RNA known as NC886. Even though the consequences of this epigenetic change aren't quite apparent because of the function of NC886 aren't really known, I use this study as an example to highlight how preconception exposure of mothers and probably fathers To diet and lifestyle factors like alcohol consumption can potentially affect long-term health of their babies.

It's never too early to start thinking about this stuff, especially if you're planning on having children. Maternal alcohol consumption can clearly have direct impacts on the developing fetus or her own eggs as they grow and mature. However, paternal alcohol consumption can also affect a child's health through epigenetic effects. For example, rodent studies have shown that offspring from alcohol-treated fathers have lower birth weights, lower individual organ weights, smaller brains, and impaired cognitive and motor abilities compared to non-alcohol-treated fathers. The sperm epigenome is very sensitive to environmental exposure, which likely explains why paternal alcohol consumption patterns can influence offspring phenotypes so strongly.

Talking about all of the epigenetic modifications that have been studied is beyond the scope of this conversation. But I will note that the literature in rodents and humans indicates that DNA methylation is sensitive to paternal alcohol exposure. Alcohol also impacts chromatin, the genetic material comprising our chromosomes, and non-coding RNAs in sperm. As I mentioned earlier, it's clear that avoiding alcohol while you're trying to get pregnant and especially during pregnancy, is the best way to increase your chance of a healthy pregnancy and a healthy child. That goes for the mother and father. There is not a lot of human research on the epigenetic changes associated with maternal and paternal alcohol consumption or what the implication of certain epigenetic changes are.

But it does seem that even pre-pregnancy alcohol consumption by the mother and father can alter long-term health of the children in utero and even into puberty. So let's quickly recap. For women, any amount of alcohol is associated with lower odds of achieving a pregnancy and lower egg quality. For men, the relationship between alcohol and erectile dysfunction or fertility is less certain. Consuming 1 to 7 drinks per week may not impact sperm quality and even seems to protect against erectile dysfunction while higher levels reduce sperm quality. My recommendation based on the literature, if you're trying to get pregnant, Lower your alcohol intake considerably, preferably stop altogether at least 3 months before really trying to get pregnant. There's no evidence that even a low consumption of alcohol will improve fertility outcomes in men or women.