Unlike men who continue to produce sperm throughout their lives, women are born with their full complement of eggs (oocytes, ovum), normally in excess of 1 million egg bearing ovarian follicles. At the onset of puberty the number of eggs has been reduced to 300,000 to 500,000 and during the next 35 to 40 years of reproductive life a women will ovulate  (release and egg) 400 to 500 times and the rest of the follicles will undergo atresia. Atresia refers to the hormonally regulated degeneration and subsequent resorption of one or more immature ovarian follicles. Atresia is a process that continues through a women’s reproductive life regardless of whether a women has regular menstrual cycles, is pregnant or uses birth control. The egg bearing follicles will ultimately be depleted to a point at menopause that only a few hundred remain.

During the reproductive years most women ovulate monthly. If the egg is fertilized and implants in the endometrium, the liming of the uterus, pregnancy ensues. If fertilization and implantation do not occur the hormone thickened endometrium will be sloughed off in the form of menstrual flow.

Physiology

The reproductive (menstrual) cycle refers to the maturing and release of an egg and to the preparation of the uterus to receive and nurture and embryo.

The cycle is controlled by the hypothalamus in the brain. Neurosecretory cells in the hypothalamus produce the gonadotropin-releasing hormone (GnRH) that acts on the cells of the pituitary gland which in turn secrete gonadotropins, FSH & LH. FSH is the follicle-stimulating hormone - LH is the luteinizing hormone. Both FSH & LH stimulate and control cyclic changes in the ovary (ovarian cycle). The hormones estrogens and progesterone are produced by the ovaries under the influence of FSH and LH and simultaneously promote the cyclic changes in the structure and function of the endometrium, the lining of the uterus, (menstrual cycle). Thus, the cyclical activity of the ovaries is intimately timed with changes in the uterus so that after fertilization of the egg occurs, the endometrium is prepared for the implantation of an embryo. Development of the follicle bearing egg, fertilization, and implantation of the fertilized egg in the receptive endometrium, must be exactly timed or pregnancy will not occur.

The reproductive cycle generally lasts 28 to 32days and is divided into three distinct phases: the follicular phase, the ovulatory phase and the luteal phase.

The follicular phase, which begins on the first day of menses lasts approximately 10 to 14 days and is the period the egg-bearing follicles grow and develop. GnRH released by the hypothalamus signals the pituitary gland to release FSH, which in turn stimulates the growth of several ovarian follicles. One follicle, in one of the two ovaries, will be selected to be the dominant follicle and its egg will selectively mature. The other follicles will undergo atresia and be resorbed. As the dominant follicle increase in size it releases increasing amounts of estrogen in to the bloodstream creating a feedback that signals the hypothalamus and pituitary to reduce the production of FSH. The dominant follicle, also known then as the graafian follicle, ultimately reaches a diameter of up to 25 mm. Around day 14 the proliferative phase ends with the LH surge.

In the early follicular phase, after menstrual flow has ended, the lining of the uterus is at it thinnest. Levels of estrogen are at their lowest. Later in the follicular phase, as estrogen rises proliferation (or thickening) of the uterine lining (endometrium) occurs. This thickened lining is preparing for a possible pregnancy.

The ovulatory phase begins with the LH surge and ends approximately 36 hours later with ovulation. Ovulation is the release of the egg from the dominant follicle into the fallopian tube, where it awaits fertilization by the partner’s sperm. As the dominant follicle grows toward the end of the proliferative phase increasing amounts of estrogen trigger the pituitary gland to release a surge of luteinizing hormone, LH. Detection of LH in the urine is the basis of ovulation prediction kits and indicates that ovulation will occurs within the next 36 hours. An egg lives 12-24 hours after leaving the ovary so intercourse must occur prior to or at ovulation if pregnancy is to occur. Sperm can wait for the egg but the egg cannot wait for sperm. Among healthy women trying to conceive, nearly all pregnancies can be attributed to intercourse during a six-day period ending on the day of ovulation. Sperm that have entered the cervical mucus are nourished there and can survive for long periods, certainly, for several days after intercourse. Once in the cervical mucus, they are stored in the crypts and are propelled upwards, in waves from the cervix to the uterus and fallopian tubes, over a period of 48 to 72 hours. Thus, the cervical mucus acts as a sperm reservoir.

The luteal phase begins at ovulation and lasts for 14 days. After the egg has been released from the dominant follicle it closes and this empty sac becomes known as the corpus luteum. The former dominant follicle accumulates a yellowish pigment, lutein, that lends its name to the process of luteinization and the corpus luteum. In the 14 days of corpus luteal life, which is dependent on low but continuous quantities of LH being available, the corpus luteum secretes the hormones progesterone, androgens, and estrogens. Secretion of large quantities of progesterone marks the luteal phase. By day 8 or 9 after ovulation, peak development of the corpus luteum occurs, and peak levels of progesterone and estradiol are seen. Progesterone causes the lining of the uterus, the endometrium, to enter the progestational (or secretory phase) in preparation for implantation of an embryo.

If the egg (oocyte) is fertilized and implantation occurs, degeneration of the corpus luteum is prevented by the emergence of a new stimulus, human chorionic gonadotropin (hCG), an LH-like hormone produced by the developing embryo and secreted into the maternal blood stream. A rapidly rising hCG is the sign of a healthy pregnancy. Since implantation in the endometrium normally occurs about 6-7 days after ovulation, hCG stimulus must appear at the peak of corpus luteum development (by the 10^th day after ovulation), just in time to rescue the corpus luteum and prevent luteal regression. hCG, produced by the embryo and secreted into the maternal bloodstream is the substance that is detected in pregnancy tests.

In early pregnancy, hCG maintains the vital steroidogenesis (production of sex hormones) of the corpus luteum until approximately the 10^th week of gestation, by which time secretion of progesterone and estrogen by the placenta becomes adequate for maintenance of pregnancy. The corpus luteum regresses slowly after the 10^th week of pregnancy.

Fertilization and Pregnancy:

After traversing the cervix and reaching the fallopian tube sperm can fertilize an egg. Fertilization is the process by which male and female gametes fuse to form the zygote (a unicellular embryo). Fertilization usually takes place in the ampulla, the widest part of the fallopian tube, 12 to 24 hours after ovulation. After this period of time, the egg loses its ability to be fertilized and begins to degenerate. If fertilized, the resulting embryo reaches the uterus about 3-4 days later in the morula stage (12 to 16cells) and implants in the endometrium on the 6^th or 7^th day as a blastocyst (pregnancy).

If fertilization does not occur degeneration of the corpus luteum is inevitable. Failing an increasing source of hCG from a successful implantation, the corpus luteum rapidly declines 9-11 days after ovulation. Its vascularity and lipid content wane, it begins to shrink and degenerate. Simultaneously, progesterone production decreases, precipitating menstrual bleeding by the shedding of the compact and spongy layers of the endometrium. The luteal phase of the cycle is thus regulated by the limited 14-day functional lifetime of the corpus luteum. The entire system then resets and a new cycle begins.

It’s no exaggeration to say the current obesity pandemic threatens to overwhelm the American and Global Health Care System by contributing to illnesses such as diabetes and heart disease. Obesity, which diminishes both the quality of life as well as life expectancy, is the leading risk factor for the most common form of diabetes, Type 2 diabetes. Type 2 diabetes is a chronic condition that affects the way the body metabolizes sugar (glucose). Specifically, type 2 diabetics become resistant to the effects of insulin; the hormone that regulates the absorption of sugar into cells. Type 2 diabetes develops when the production of insulin is insufficient to overcome the underlying problem of insulin resistance.  The early stages of the disease are characterized by an overproduction of insulin. As the disease progresses insulin levels may fall as a result of the partial failure of insulin producing Beta cells in the pancreas.

Type 2 diabetes was traditionally confined to adults and was once called adult-onset diabetes; that is no longer the case. Today some obese children develop type 2 diabetes even before the onset of puberty. A recent study demonstrated that 25% of obese children are already glucose intolerant (pre-diabetic insulin resistance) and at a high risk of developing frank diabetes.

There are 23.6 million diabetics in the United States, roughly 8% of the population and as a result of the obesity pandemic there numbers are growing dramatically. For example, the total prevalence of diabetes increased 13.5% between the years 2005 and 2007. According to the American Diabetes Association one out of every five health care dollars is spent caring for someone with diagnosed diabetes, while one in ten health care dollars is attributed to diabetes per se. This should not be all that surprising given the propensity of diabetics to develop complications. The most life-threatening consequences of diabetes are heart disease and stroke, which strike people with diabetes twice as often as normal individuals. In diabetics these complications occur at an earlier age and are more likely to be fatal. Diabetes is the leading cause of new cases of blindness in people ages 20-74. Diabetes is also the leading cause of end stage renal disease accounting for 43% of new cases and make up the largest group that undergoes dialysis and kidney transplant. More than 60% of non-traumatic lower-limb amputations occur among diabetics. Other complications include impotence, depression and nerve damage. Clearly, weight gain and the resultant rise is diabetes has a devastating impact on the health of Americans.

Weight gain results from an energy imbalance. Simply stated this involves taking in to many calories and not getting enough exercise. The medical solution is at least in theory easy, loose weight and avoid this catastrophic end. Studies have clearly shown that increased physical activity reduces the risk of developing type 2 diabetes regardless of the degree of adiposity (fatness). Exercising to an intensity of 80–90% of age-predicted maximum heart rate for at least 20 minutes, at least five times per week has the potential to substantially enhance insulin sensitivity. Even modest weight loss in the range of 5-10% of initial body weight and regular exercise has been shown to reduce the risk of diabetes by 58% over a three-year period.

Eat less and exercise more has been the mantra for the last several decades but the message seems to have been lost on the 60+% of Americans who are overweight. What will it take to put a halt to this mushrooming health care time bomb - probably nothing less than a no-holds-barred campaign similar to anti-smoking campaign of the last three decades?  At the risk of being unpopular in some circles the following should be at least considered:

1.     Portion Control - After having lived in Europe for more than 15 years the most shocking change I found on my return to the U.S. was the sheer size of portions served in U.S. restaurants. A 400-gram (13.5oz.) steak is more than any adult should eat - do we really need to have 22oz and 24oz steaks on the menu?

2.     It’s all about sugar and fat. A “Big Mac” and a Coke on occasion seems reasonable, but as a steady diet the only thing that will be supersized is the child.

3.     Just walk - do it for your health or to save the planet from global warming but just do it. Who knows tomorrow you might just start to run.

4.     Here is where I get into real trouble - After some reasonable grace period to correct the problem e.g. one-year, overweight and obese people should be charged higher health and life insurance premiums. The rationale is no different than higher premiums for smokers. Just like smoking, the voluntary action of eating to much, eating the wrong foods, and not exercising costs the rest of the population a great deal of money. If we won’t loose weight to improve our health and save our own lives the rest of the population should not be unduly burdened with the excess cost. Hopefully, this will be a concrete incentive to loose weight and exercise. While this may sound punitive, concrete action like this helped to reduce smoking.

5.     Reluctantly, I would recommend a tax on high calorie fast food. Making cigarettes more expensive clearly reduced the number of people who smoked. To be fair and provide a further incentive we should rebate that tax for each portion of “healthy food” that is substituted for the traditional fat meal.

6.     Education at all levels, in schools, at work; in public service advertising we must address the seriousness of this issue.

The only thing we can’t do is continue to do what we are doing because it clearly has not worked.

What should be obvious, seems lost in the political rhetoric, we don’t have the physicians, nurses and other health care professionals to actually provide quality universal health care despite the fact that we spend more, per capita on health care than any other country in the world. In the U.S. we spend approximately $6,000 per capita as compared to about $3,500 countries with universal national health care systems such as France and Germany. In fact, we spent $2.2 trillion in 2007 on health care, or 16.2% of our gross domestic product (GDP).

We appear to be poised to add about 46 million uninsured patients to the system over the next few years or a population greater than the size of Spain.  If we make the reasonable assumption that American physicians currently work a full day; who is going to treat this new influx of patients. While it may overstate the case to say that these patients are not receiving any healthcare, it is instructive to calculate how many physicians would be needed to treat 46 million additional patients. In the U.S. we have approximately 3.0 physicians per 1,000 people thus, if we extrapolate we would need an additional 138,000 physicians to treat this population.

We are already behind the curve; there were 15,242 medical school seniors in 2008 to fill approximately 22,000 residencies. Not surprisingly, roughly 4,650 were filled with foreign graduates, some of whom were Americans who had studied abroad. The balance was filled with graduates of osteopathic schools. The medical-colleges association has called for a 30% increase in enrollment by 2015 as compared with 2002 primarily by expanding existing schools and opening new campuses. This goal may be unachievable. Thus, in the future, larger numbers of foreign medical school graduates will be needed to meet our needs since, expansion of medical education Is unlikely keep pace with the increased need for physicians.  For example, the medical-college association estimates that if physician supply and use patterns stay the same, the United States will experience a shortage of 124,000 full-time physicians by 2025.

The question we must answer is - will we continue to get the high quality medical school applicants in a world in which the government will play and increasingly important role either directly though programs such as Medicare and Medicaid or indirectly by setting the standard of reimbursement which is likely to be emulated by private insurance companies? Given the run-away costs in the American health care system there is likely to be significant downward pressure on physician reimbursement. This comes at a time when it costs approximately $200,000 including living expenses to attend medical school in the U.S. A recent study published in the New England Journal of Medicine estimated that 23% of medical school graduates begin there professional life with $200,000 or more of debt from pre-med and medical school loans. In addition, a substantial number have over $100,000 in debt by the time they graduate. At what point is it uneconomical to become a U.S. physician knowing that government is dedicated to reducing its expenses by limiting the income a physician can earn?

Medical students in Europe, where national health programs are virtually universal do not pay to attend medical school, the government who in a very real sense limits the ability of these future doctors to earn a living, has made a implicit bargain with the students; education is free but the government reserves the right to determine your level of compensation throughout your professional career. At the moment, the American medical student is asked to go into hock for $200,000 or more while their ability to control their level of compensation once they graduate may be determined by government bureaucrats.  Americans are likely to perceive such a system a inherently unfair, and may insist that the either the government pay for medical education or refrain from limiting the free market in medical reimbursement.

In 2008 the number of students applying to medical schools dropped by 3% according to the Association of Medical Colleges at a time when American medical schools are being urged to accept more students to counter the projected shortage of physicians.

Given the economic uncertainty that lies ahead for physicians it would not be surprising to see a precipitous drop in high-quality medical school applicants. After all, these bright young men and women can become investment bankers, lawyers, engineers etc. and not be subject to government restrictions on their ability to earn a living.

If we are to continue to attract our best and brightest to medicine a national policy that, is perceived to be fair must be developed.