All people need fat, protein, and carbohydrates. All people need regular exercise. All people need to sleep. But not all people need the same amount of the same things employed in the same way. The majority of health recommendations are based on what’s best for most people most of the time according to the latest research, but humans are subject to biological diversity. That diversity starts with biological sex.
Dr. David Sinclair writes in Lifespan: Why We Age—and Why We Don’t Have To, “We’re all too slowly coming around to the shameful recognition that, for most of medical history, our treatments and therapies have been based on what has been best for males, thus hindering healthy clinical outcomes for females. Males don’t just differ from females at a few sites in the genome; they have a whole other chromosome” (emphasis mine).
So much of our sexual diversity has to do with reproductive health. The average female menstruates from puberty to menopause, and the cycle affects everything from macronutrient needs to sleep efficiency to the body’s basal temperature, month after month after month. That doesn’t begin to touch on the physiological changes women endure while pregnant, breastfeeding, or perimenopausal (conditions that are also important to female longevity, but out of scope for this article). Even when women aren’t planning to have children and/or have no desire to do so, the ability to have a child is directly related to their health.
For males, they have to figure out a half-teaspoon of semen volume upon ejaculation. That’s it. Reproductive health is not a niche subject for women. It may hold the key to female longevity and it’s important for us to talk about it.
Below, I’ll cover the basics of what the menstrual cycle actually is. Then I’ll go over why menstrual cycle tracking is important, and how hormonal birth control is an important consideration for women interested in life extension. In the second article in this series I’ll examine and compare the best period tracking apps and tools.
Let’s get started!
The menstrual cycle and female longevity
If you have a period, there is never a point in time when you’re not in your cycle. Every cycle is different—things like genetic variations, lifestyle choices, birth control, environmental factors, and illnesses can all affect how an individual experiences menstruation.
“Cycle” is a bit of a misnomer, as there are two intersecting cycles throughout the menstrual cycle: the ovarian cycle and the uterine cycle. The ovarian cycle describes what happens to the follicles of the ovary, whereas the uterine cycle describes what happens to a uterus’ lining, known as the endometrium.
We’ll cover both as we move through the menstrual cycle, which typically lasts 21–35 days.
The uterine cycle starts with menstruation. During this phase, women shed blood and endometrium. It’s normal to lose two to three tablespoons of blood over the course of a week.
The follicular phase
The ovarian cycle starts with the follicular phase on the first day of your period. It ends when you ovulate. Your brain’s hypothalamus sends a signal to the pituitary gland to release follicle-stimulating hormone (FSH). FSH communicates with the ovaries to ready some eggs for release. Eggs grow inside follicles (hence “follicular” phase), and follicles also release the hormone estrogen.
The proliferative phase
During the second phase of the uterine cycle, estrogen causes the uterine lining to grow and thicken (or “proliferate”). The uterus does this so that a potential fertilized egg has a place to implant and safely grow. Estrogen also stimulates cervical mucus, the source of normal, odorless vaginal discharge.
About halfway through the menstrual cycle, an egg is released into the fallopian tube. An acute rise in luteinizing hormone (LH) matures the egg. Ovulation typically lasts 48 hours. If the egg is not fertilized during ovulation, the menstrual cycle continues to the luteal phase.
The luteal phase
During this ovarian phase, the now-empty follicle transforms into the corpus luteum (luteum as in luteus, meaning “yellow”), which produces both estrogen and progesterone. The hormones produced by the corpus luteum also suppress both follicle-stimulating hormone (FSH, first seen in the follicular phase) and luteinizing hormone (LH, first seen in ovulation). FSH and LH fall rapidly, which causes the corpus luteum to decline and break apart. Hormonal changes during the luteal phase often cause common premenstrual symptoms like cramping and migraines. Once the corpus luteum atrophies and estrogen and progesterone levels consequently drop, menstruation begins again.
The secretory phase
The final phase of the uterine cycle corresponds with the luteal phase. While the corpus luteum produces progesterone, it makes the uterine lining (endometrium) receptive to implantation during early pregnancy. The endometrium secretes a host of prostaglandins, which cause the uterus to contract. Two prostaglandins in particular, PGF2α and PGE2, cause cramping and also help trigger menstruation.
From there, the menstrual cycle starts again.
What’s so important about the menstrual cycle for female longevity?
Before digging into the research, I looked forward to menopause for one important reason: no more crampy, white-pants-ruining, week-long periods. Now I’m a little more apprehensive (and hope it never happens because I’m down with human life extension).
Researchers publishing in the Journal of Mid-Life Health explain what the menstrual cycle has to do with female longevity:
Natural menopause has been defined by [the] World Health Organization (WHO) as at least 12 consecutive months of amenorrhea not due to surgery or any other cause. The mean age at natural menopause (ANM) is 51 years in industrialized nations, while it is 48 years in poor and non-industrialized nations. Menopause is not a central event but rather a result of primary ovarian failure secondary to apoptosis or programmed cell death. … This results in reduced production of estradiol, the most active form of estrogen as well as increased levels of follicle-stimulating hormone (FSH) and decreased levels of inhibin. … The ANM remains an independent risk factor for long-term morbidity and mortality.
In other words, menopause is caused by the same age-related stuff that results in cancer, Alzheimer’s disease, and cerebrovascular disease: an accumulation of molecular and cellular damage over decades of life. Menopause results in shorter reproductive healthspans, heightened risks of endometrial cancer, increased risk of stroke and osteoporosis, and increased combined cardiovascular risk factors.
As obnoxious as periods are, women are generally healthier with them (amenorrhea is also associated with pituitary tumors, PCOS, hypo- and hyperthyroidism, and plain ‘ole stress). If you menstruate, it’s within your best interest to keep menstruating.
Incredibly, menstruating indefinitely may be a possibility.
There’s recent evidence that challenges the fatalist consensus that human females are born with a set number of eggs and that menopause is a result of running out of them.
For example, in 2004, Dr. Jonathan Tilly of Northeastern University published a study in Nature documenting a group of stem cells in mice that supported new egg production—a first in mammal studies. Dr. Tilly reproduced that study in 2017. A related press release explains,
To track the cells, researchers genetically engineered them to express a certain gene—the same one that makes jellyfish glow fluorescent green. The scientists then reintroduced the genetically engineered cells back into the ovaries of adult mice. The proof that new eggs had been formed with the modified cells was undeniable—the baby mice were born green.
Studies like these have become a point of fascination for researchers like Dr. David Sinclair (who argues, with some evidence, that NMN supplementation will be a key factor in maintaining and regenerating the menstrual cycle) and Aubrey de Grey. In fact, in 2014, de Grey famously argued that menopause will be a thing humans can “turn on and off” in the following twenty years.
What about hormonal birth control and female longevity?
Well over half (60%) of women of reproductive age are using birth control, and most of those women (72%) use some form of hormonal birth control. It’s mind boggling to me that when almost half of all US females aged 15–44 are using hormonal contraceptives, it’s not better studied or controlled for in life-extension research. Females, in many of these studies, are treated as males with different sex organs, when the reality is that the menstrual cycle and any hormonal birth control can deeply affect the outcome of research.
Here’s what we do know: hormonal birth control, regardless of the user’s chosen method can affect one’s quality of life. For example, one study found that hormonal birth control improved the everyday quality of life among college-aged women. The study found that women who use contraceptives have sex more frequently (the causal factors are disputed in the article), have less premenstrual breast tenderness, and, of course, worry less about pregnancy for those engaged in intercourse.
On the other hand, another study from Fertility and Sterility found that women aged 18-35 often become more depressed when taking oral contraceptives in a double-blind, randomized, placebo-controlled trial. The research found that participants taking 150 μg levonorgestrel and 30 μg ethinylestradiol (like brand names Levlen, Microgynon, and Alesse) overall had a lower sense of positive well-being, self-control, and vitality. One in five participants taking oral contraceptives (21%) had bodily disturbances, including bleeding disturbances, anxiety and mood changes, acne, and appetite changes—all of which are moderately unsurprising, since those are all known side effects of taking hormonal birth control pills.
In the long term, it’s unclear whether hormonal birth control is a net positive or negative. For example, hormonal contraception correlates with a slight but statistically significant increase for the risk of developing breast cancer. Use of birth control for five years or more also correlates with higher rates of cervical cancer. However, a 2010 cohort study published in the British Medical Journal also found that people who took any birth control had a significantly lower rate of death from any cause, and that there’s a potential protective effect, causing “significantly lower rates of death from all cancers; large bowel/rectum, uterine body, and ovarian cancer; main gynaecological cancers combined; all circulatory disease; ischaemic heart disease; and all other diseases.”
That said, the researchers caution that their findings may not be true for future generations; the study included women who took first-generation hormonal birth control, which contained far more estrogen than what’s available today. A final study published in Studies of Family Planning found that “women who take oral contraceptives for five years before the age of 30 can expect to live about four days longer” than those who didn’t.
What this data says to me is that it’s a body-by-body decision.
I, personally, can’t take estrogen-based birth control because I have Factor V Leiden—a genetic disorder that puts me at greater risk for abnormal blood clots. I’ve used non-hormonal contraceptives, progestin-only birth control pills, and the implant (Implanon and then Nexplanon). I’m currently not using any hormonal contraceptives, but that may change as more long-term progestin-based longevity research emerges.
What else do women need to know about life extension?
I expect that the menstrual cycle and hormonal birth control will play a greater role in life-extension research as the longevity community grows and evolves. I’m particularly excited about the work Drs. Francesca E. Duncan, Lei Lei, and Shiying Jin are doing at the Buck Institute and continued work from Dr. Jonathan Tilly. That said, there’s still so much to be done.
In the meantime, women should be aware that there’s significant medical research bias that leads “general recommendations” to be “general recommendations for men.” An older but important study found that the biggest reasons for gendered research bias is caused by:
- A general poor understanding of the metabolism and physiology of childbearing-age females.
- A desire to base current studies on previous findings, which were historically comprised of predominantly male populations.
- Budgets that limit the inclusion of women—testing and tracking women is simply more expensive.
Twenty years later, you’d think that the legislated requirement of including women in clinical trials would create more nuanced medical recommendations from newer clinical trials. That hasn’t entirely been the case. For example, a 2017 meta-analysis of 2,700+ case reports showed a “statistically significant gender bias against female case reports.” In other words, women should take all longevity recommendations with a bit of skepticism; metformin and intermittent fasting affect women differently than men, and aspirin was found to extend life in male mice it did not do the same for females. Women must be more vigilant than men when checking the underpinning research for life-extension advice.
What considerations have you made for your menstrual cycle when approaching life extension? What about birth control? Or reviewing the scientific literature? Help your fellow spanners out with tips and recommendations in the comments below.
And tune in in two weeks when we cover the top period tracking apps for you to manage things yourself!