It’s Not Just Venus or Mars Anymore

Dec. 5, 2014

By Medical Discovery News

It's Not Just Mars or Venus Anymore

While the gender gaps are closing, sometimes the differences between men and women seem as great as the differences between Venus and Mars. For example, men and women tolerate medications very differently. Due to this, the Food and Drug Administration (FDA) has recently changed the recommended dosage of the sleep aid Lunesta from two milligrams to one milligram because of its prolonged effects on women.

Women reported feeling drowsy in the morning hours after waking, raising concerns about the hazards of driving and working. While men and women are often prescribed the same dosages of medications, this case shows how men and women are not the same organism and drug dosing might need to take that into consideration.

For basic studies in the biomedical laboratory, many cells lines that are used experimentally are derived from tissues obtained from males, either human or animal. Even in the very early steps of identifying a drug and determining how it works, efforts are already focused on those of us with a Y chromosome.

Clinical trials are conducted before a new drug can be approved, and trials also favor males. In fact, white males remain the predominant subjects for drug trials today. Women were initially avoided in clinical trials because of concerns that they were pregnant or would become pregnant. Women also have cyclic hormones that alter metabolism and could interact with drugs. While this is precisely why women’s tolerance of a drug should be tested prior to its approval, researchers thought this complicated the early stages of the process. Once a drug is launched, the number of people using the drug expands and these side effects start to be reported. While an individual physician may notice patients have side effects, they do not have a wide view of the whole population’s reactions.

Pharmokinetics is the study of what happens to drugs administered to a living organism, and could explain some reasons why men and women handle the same medication differently. For starters, men and women have a number of basic physiological differences. Firstly, women tend to have a lower body weight and body volume. Therefore, the concentration of a drug is often higher in a woman. Women also have a lower gastric emptying, slower gastrointestinal motility, and different absorption rate that can alter the amount of a drug that gets to the blood and is distributed throughout the body. They have different glomerular filtration in their kidneys, which reduces the rate at which drugs are cleared out of the body and therefore leads to higher and more prolonged drug levels. Women experience greater sensitivity to beta blockers, which are used to treat heart conditions; opioids, which are used to control pain; and antipsychotics.

The pharmacodynamics (how drugs function) in female and male bodies can be quite different also. Aspirin is a great example. It is less effective at lowering subsequent heart attacks in women when given the standard preventive dose. They may need higher doses to prevent a second cardiovascular episode.

Recently, the National Institutes of Health (NIH) has required that all cell, animal, and human studies it funds have a balanced representation of both genders. While this may increase the cost of developing therapeutics, it will certainly expand our understanding of how medicines affect the genders differently and improve drugs for everyone.

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What Makes a Male?

May 16, 2014

By Medical Discovery News

What makes a male?

Despite centuries of women being celebrated for siring sons, or scorned for failing to produce an heir, it is actually men who determine a baby’s gender. Women give each of their offspring an X chromosome, but the male can give an X or a Y chromosome to create a female (XX) or male (XY), respectively. But how much of the Y chromosome is required to make a male? It turns out only two genes are needed to create a male mouse, a species that determines gender the same as humans. 

Humans have 23 pairs of chromosomes, one of which is the sex chromosome. Chromosomes contain lots and lots of genes, all which carry instructions that tell different parts of the body what to do. In males, the Y chromosome carries a gene called SRY that encodes the Sex-determining region Y (also abbreviated SRY) protein. This protein, as its name suggests, will decide the sex of future offspring. Consequently, this one single gene, SRY, is all that’s required to produce an anatomically male mouse. However, these male mice are infertile because they lack some of the genes involved in sperm production.

That’s where another gene called Eif2s3y comes in. With this second gene, male mice can at least generate sperm cell precursors known as round spermatids, but not mature sperm. To fully develop sperm, the mice need both copies of this gene. One is toward the end of the Y chromosome and the other version is on the X chromosome.

So with only two genes from the Y chromosome, male mice are able to produce immature sperm. Scientists used an assisted in vitro fertilization technique to treat male infertility by injecting the round spermatids directly into the eggs of female mice. The round spermatids fertilized the eggs nine percent of the time. In comparison, sperm from natural-born male mice fertilized eggs 26 percent of the time. The offspring born from these efforts developed into normal, healthy, fertile adult mice. 

Even though only two genes from the Y chromosome are required to produce fertile adult mice, the Y chromosome is still important. More genes are required to produce fully mature, motile sperm capable of fertilizing an egg without intervention. The Eif2s3y gene may play a role in some forms of male infertility in humans. With this new data, therapies could be invented to encourage the development of functional sperm that could reproduce through in vitro methods. Injecting round spermatid into eggs is not currently an option for humans due to technical and safety issues, but this technique is likely to get better with additional research. 

The genetic information contained in the Y chromosome plays important roles in reproduction by controlling the development of sperm and normal fertilization and will continue to do so, negating suggestions that it is being eliminated by evolution or rendered useless by in vitro fertilization. For now at least, men remain indispensable.