At the age of twelve or so, the pulse generator in the hypothalamus is resuscitated, disinhibited. It begins squeezing out packets of hormones again. Just as we don't know what shut it off before kindergarten, we don't know why it starts ticking again. Perhaps cues from the adrenal gland have stimulated it. Or fat may be the culprit. Fat cells release a signaling molecule called leptin, and some experiments have suggested that leptin is the switch that reactivates the brain clock. It is possible that the brain adjudges reproductive readiness by a girl's fat content, and that a girl must attain a certain level of fatness, a certain heft, before she is capable of ovulating. One rule of thumb has long had it that when a girl reaches approximately one hundred pounds, she pubesces, regardless of her height or even her age. Fat girls menstruate earlier than thin girls or athletic girls. If a quarter of those hundred pounds are fat, then we're looking at twenty-five pounds of fat, which represent an energy reserve of 87,000 calories. The demands of pregnancy are about 80,000 calories. In theory, then, the brain may assess the leptin levels leaking forth from a growing girl's adipose tissue and start its metronome beating again at the hundred-pound mark.
Whatever the trigger, the revived hypothalamus is stronger now by far than it was in its nursery days. And stronger still are the ovaries, the gray sacks of heirloom pearls. They are ready to roll. The adrenals can go only so far. The ovaries know no bounds. They are the primary source of sex hormones that sexualize the body. Before the ovaries are able to serve up a viable egg, they are quite adept at dishing out the sex hormones. The sex hormones cause pubic hair to grow, fat to gather on the breasts and hips, the pelvis to widen, and eventually menstrual blood to flow.
If you are like me and you've been reading for years about the ovulatory cycle, you find it tedious. You've seen the charts of the rise and the fall of hormones, most of them with fusty names that sound like nothing you feel or think about or know of your body. Luteinizing hormone, LH; follicle-stimulating hormone, FSH; the worst of them, mentioned above, gonadotropin-releasing hormone, or GnRH. The cycle is disembodied from the cyclist.
Please, put aside your bigotry. Far from being dull, the cycle is dynamic and athletic. In describing it, I run the risk of sounding like a Victorian anatomist. Those scientists were astounded by the ovarian cycle. Some were simply fascinated by it; others were disgusted by it. All wrote gothically of it, and found in the monthly follicular rupturing and oozing yet another reason to pity the fairer, better, bruised and battered sex. Rudolf Virchow, the father of modern pathology, compared the bursting of the follicle to teething, with the egg forcing its way to the surface of the ovary as a tooth bud pokes through the gums, causing pain and "the liveliest disturbance of nutrition and nerve force." French doctors likened ovulation to the rupture of an acute abscess, while Havelock Ellis saw the monthly release of an egg as a "worm" that "gnaws periodically at the roots of life." In the eyes of the historian Jules Michelet, Thomas Laqueur writes, "woman is a creature 'wounded each month,' who suffers almost constantly from the trauma of ovulation, which in turn is at the center of a physiological and psychological phantasmagoria dominating her life." The ovary may be an almond in size, but for the voyeurs among Victorian physicians, it certainly was no almond of joy.
To me, the swelling of the ovarian follicle and its release is less ghoulish, less an act of carnage, and more in keeping with many acts of reproduction, sexual optimism, and high emotion. The follicle swells like a lobule in the breast swells with milk, or like the tear ducts swell with water and salt, or like the genitals congest during arousal—and then whoosh, the tension is released, and the lively fluids overspill their bounds.
Let us take as our starting point the standard day one of the ovulatory cycle (which we generally call the menstrual cycle because we can see the blood but we can't see the egg). Day one is the first day of menstruation, a quiet time for the ovaries. They release no eggs and generate very few, if any, sex hormones. Quiet below means flurry above, in the pulse generator of the hypothalamus. With scant evidence of hormonal output from the ovaries, the pulse quickens. The hypothalamus sends forth its messenger, the brain hormone GnRH, which in turn prods the pituitary gland, right below it. The pituitary expels its own parcel of hormones, and now we return to the young gray ladies, the seedpods. The pituitary signals awaken them. The pods are a collection of follicles, little nests, each enclosing an immature egg, as the honeycomb cells of a beehive enclose bee larvae. Every month, about twenty follicles and their oocytes are hailed by the brain. They start to expand and to ripen. They are like starlets at an audition, their heads stuffed with dreams. Eventually, on day ten or so, a decision is made. One of the contending follicles is chosen for the part. Its egg alone will advance to full fruiting, to the point of ovulation. (On occasion, more than one egg matures in a cycle, which is why we have fraternal twins, triplets, human litters.) Nobody knows how the selection is made. The winning follicle may simply be the one that grew fastest from the start. Or it may have released cues early on as to the genomic acuity of its oocyte and so have been singled out for grooming. However the sifting happens, the other follicles recognize when they have lost, for on the tenth day they cease to swell and start to wither, taking their rejected eggs with them. The chosen follicle persists. The egg within it matures, and its chromosomes are sorted out through meiosis. By the final stages, the follicle is so engorged, so grandiose, that it measures an inch across and half an inch high.
The swelling of the ovarian honeycombs is an exhibitionist act. It attracts attention. The fallopian tubes, those gorgeous pink sea pens, follow the drama with their feather-duster tips. As the follicles grow, the tubes brush over the surface of the ovaries, firmly, insistently, seeking clues—the envelope, please, which follicle will it be? The tubes are extraordinarily flexible. They are like the arms of an octopus, or vacuum cleaner hoses. Although each tube generally attends to the ovary closest to it, one tube can, if necessary, reach across the pelvic cavity to finger the opposite ovary. This happens in a woman with endometriosis, for example, when one of her two tubes is lashed down by a tangle of stray uterine tissue and cannot sample its seedpod. The opposite tube takes up the task of monitoring and snuffling the surface of both ovaries. And when the selected egg is ready, on one ovary or the other, the lone mobile tube will be there to catch it.
The final signal for ovulation, for the liberation of the egg, comes again from the brain, on day twelve or fourteen or thereabouts, with a spurt of luteinizing hormone from the pituitary gland. The hormonal surge persuades the follicle to split open. Sometimes a little blood is released on rupture, the spotting of ovulation that may come with mild cramping, the mittelschmerz. The egg sails out, into the waiting fingers, the fimbriae, of the fallopian tube. The fimbriae are covered with hairlike projections that beat in synchrony and create a current to suck the egg into the tube, the fertility hutch.
(Any woman who has ever used an ovulation predictor kit in an attempt to get pregnant knows of the LH surge, because it is the detection of the surge that tells her, Have sex today, as soon as possible; your egg is ready to pop. Whether the surge is the ideal event to shoot for is open to question, though. A large study of fertility patterns published in 1995 revealed that the day of ovulation is the last possible time for conception to occur, and that most pregnancies are the result of intercourse that took place one, two, up to five days before ovulation; sperm is built to endure for days and may need time to reach the egg. The finding was surprising. Fertility experts had thought that you had at least a day and maybe two after the rupturing of the follicle to conceive, but no, the emancipated egg is either too sensitive for this world or a Mussolini for punctuality. In any event, its extrafollicular lifespan is no more than a few hours. Thus, if you wait for the LH peak to have sex, the sperm may well arrive too late. The party is over. The egg has passed out.)
Back at the gray basket, the ruptured follicle lives on. It is not a wound or a ditch. It is a new mother, in a sense, a postpartum
mother within a preparous mother. It has given birth to an egg, and now it will seek to nourish the egg. The follicle devotes itself to the production of hormones. The cells lining the pit swell, fill up with cholesterol, and turn soft and yellow, like butter or custard. They form the corpus luteum, which means "yellow body." The corpus luteum generates progesterone in great abundance and estrogens in moderate abundance, and the hormones course into the bloodstream and stimulate the uterus, causing the uterine lining to grow, and they stimulate the breasts, causing some swelling or tenderness. The fattened uterine lining could support the follicle's child, the egg, if the egg is fertilized and destined to survive, and the mammary glands could nurse the fertilized egg once it has grown and crossed over to the other side.
If pregnancy occurs, the corpus luteum will live on throughout gestation. For the first forty-two days its hormones are essential to the fetus's survival, but even after the fetus has built its placenta and the placenta assumes the task of synthesizing the hormones of gestation, the yellow body persists. It is still the dominant follicle, the crowned queen, and it keeps other follicles on the ovaries chastened, immature. One does not want to ovulate during pregnancy, after all.
But the corpus luteum is not just the equity of the possible embryo. For as long as it lasts, it is mother to the woman too. Its fat yellow tissue spills forth hormones, and those hormones impress every organ of her adult body, her bones, her kidneys, her pancreas, her brain. The body takes full advantage of the ovarian feast, as the Native Americans did with a buffalo carcass, putting each splinter of bone and strand of sinew to use in the service of food, shelter, and warmth.
In the absence of pregnancy, the corpus luteum regresses ten days after ovulation. The follicle that once attracted the stroke and suck of a fallopian tube now lures the attention of macrophages, immune system cells that clean up the body's dead and dying. Fibrous tissue forms over the pit. The corpus luteum becomes the corpus albicans, the white body, another scar on the face of experience.
The ovulatory cycle is a matter of physiology, and it occurs more or less on its own. But it is not entirely deaf to the cyclist. We don't want to make the mistake of thinking it is disembodied from the body. To the contrary, the ovaries, lacking the peritoneum and maintaining chronic contact with the brain and body, are quite responsive to us, the environment in which the organs live. The first half of the cycle is the most impressionable time. Women have very different cycle lengths, some as short as three weeks, others as long as forty days, and most of that variability occurs in the days between menstruation and ovulation. After the egg is released, the cycle becomes much more predictable. It lasts two weeks, give or take a couple of days. Before ovulation, the ovary is like an appellate court. It will listen to pleas and hear tales of denial and doubt. It will take the advice of a number of signals—from the brain, surrounding tissues, distal tissues—about what to do, whether to ovulate or vegetate. When you are very sick with the flu, for example, you may fail to ovulate, or take longer to ovulate than when you are well. This delay could be the result of the immune system's conveying a sense of crisis to the ovaries. Recall that under ordinary circumstances, macrophages are attracted to a postovulatory follicle and will help blanch the yellow body into albicans. During illness, your population of macrophages and other immune cells explodes. Some of those excess immune cells may aggregate on the ovary, disrupting the maturation of the follicles and even engulfing one or two in midswell. Alternatively, the immune changes may inhibit ovulation indirectly, by slowing the pulse generator in the brain or the secondary release of secretions from the pituitary. Whatever the details, it is not a bad system. If you're seriously ill, you need to focus on getting well. You can't afford to divert energy to a pregnancy.
Whether stress and anxiety, in the absence of frank illness, can also inhibit ovarian performance remains unclear. Popular wisdom says it does. Friends and relations frequently offer an infertile couple the unsolicited advice to relax. Take it easy, they cluck, and you'll get pregnant in no time. But this is a chicken-and-egg debate. Does stress cause infertility, or does infertility cause stress? Most of the evidence on the subject is anecdotal. We hear stories of infertile women who quit their aggravating, high-pressure jobs and quickly become pregnant, and of couples who spend years trying to conceive, finally decide to adopt, bring the new baby home, and voilà, within weeks they are with child. What we don't hear are the opposite tales, of women under horrible stress in wartime, after a violent rape, who nonetheless become pregnant. Clinical studies of the benefits of stress reduction programs to fertility treatment have yielded mixed results. Some show a significant improvement in conception rates, others show little or no difference. Primatologists seeking to understand why subordinate females in some species of monkeys, like the cotton-top tamarin, fail to ovulate when they are in the presence of the alpha female have been astonished to learn that classic stress hormones have nothing to do with the suppression of fertility. The researchers had theorized that the ruling female kept her inferiors so intimidated that the subordinates' bodies must course with stress hormones such as Cortisol, rendering them temporarily sterile. But no, urine samples from the monkeys showed an almost indétectable concentration of stress hormones in the subordinates. In fact, the opposite appeared to be true: when a junior female was removed from the alpha's territory, her Cortisol levels soared—resulting in a newfound ability to ovulate.
"Stress" in general is one of those monster topics, a source of abiding stress to those who study it. Nobody agrees on the definition of stress, how to measure it, or how much is too much. If you feel powerless in your life, a very small amount of stress can unhinge you. If you feel in control of your life, your appetite for stress may be large, bottomless. You may get high on stress and try to manufacture a perpetual state of emergency to obtain your crisis fix.
There are other ways, apart from nagging in-laws and looming deadlines, in which the outer world might impinge on the inner world of the ovaries, on the hormonal composition of the maturing follicles, on the bending and twisting and sucking of the feathered oviducts. One of the most famous and tantalizing examples of how external circumstances might influence a woman's private oscillator is the phenomenon known as menstrual synchrony: the possibility that women who live in close quarters convey some as yet mysterious signal to one another—an odorless, volatilized chemical called a pheromone—that ends up harmonizing the timing of women's cycles. The idea was first proposed in 1971 by Martha McClintock, now a biologist at the University of Chicago but then a Harvard graduate student. In a research paper that appeared in the high-profile journal Nature, McClintock presented data on the menstrual cycles of several groups of roommates at an all-female college. The women had begun the semester with cycles randomly distributed throughout the month, the way women's cycles are. Over the course of the school year, the cycles of cohabitants gradually converged. After seven months, the dates of onset of menstruation among roommates were 33 percent closer than they had been at the beginning. By contrast, among a control group of women who did not share rooms, there were no signs of menstrual synchrony. McClintock's paper won wide éclat in scientific and lay circles alike. The findings fit with many women's personal observations, the sense that mothers and teenage daughters, sisters, dorm mates, and lesbian lovers had of a mysterious coming together, of the simultaneous raiding of the tampon box, a sisterhood in the blood.
Subsequent studies of menstrual synchrony, however, were not so neat. Some confirmed the original report, others refuted it. According to one recent review of the menstrual synchrony studies published over the past twenty-five years, sixteen have found statistically significant evidence of synchrony and ten have failed to find any statistically meaningful patterns. A few studies have revealed evidence of asynchrony, or antisynchrony: as the months passed, the cohabiting women became less harmonized in their periods rather than more, sometimes to the point of diametric opposition. It's as though the women were signaling to each
other, We had nothing in common before, so please, let's keep it that way.
McClintock is a woman of verve, rigor, and high, loopy enthusiasm who wears bright scarves over cashmere sweaters and unexpected accessories, like dove-gray socks patterned with black fishes. She explores how the environment influences physiology—how nurture nudges nature. She looks, for example, at the impact of mental attitude on the course of a disease, how the belief that you can get well may influence whether you do get well. She looks at how social isolation affects health; as a rule, in social animals extended solitude affects health badly, and the questions are why and how can we measure that badness and ferret out its source, the vertex between what looks like whoo-whoo mysticism and the measurable changes in hardcore physiology. Menstrual synchrony is real, McClintock insists, but it is not the whole story. People look at menstrual synchrony and get stuck on a very narrow interpretation of it, she explained to me. They say either women's periods converge in a statistically significant manner when they live together and menstrual synchrony exists, or they don't and it's bunk.
"People focus on menstrual synchrony as the main phenomenon because it's such a compelling idea," she said. "But I can't emphasize strongly enough, it's just the left ear of the elephant. It's just one aspect of the social control of ovulation." In social creatures, she continued, fertility, ovulation, and birth occur in the context of the group. The fallopian tubes may act like little suckers, but we don't conceive or gestate in a vacuum. We are at the mercy of the tribe, and our bodies know it, and they respond accordingly. As the dynamics of the group change, so too do our reactions. To ovulate in step with our female cohorts might behoove us under one circumstance and shackle us under another. McClintock and her colleagues have found that female rats can emit pheromones that suppress fertility in other females and pheromones that enhance it. "Those pheromones can be produced at different phases of the reproductive cycle, and at pregnancy and lactation," McClintock said. "Females send out different signals depending on their state, and the females living with them respond in a variety of ways. In some cases synchrony develops, in other cases it doesn't."
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