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The Menstrual cycle and Progesterone

The Menstrual cycle and Progesterone

The menstrual cycle is a cascade of many hormones produced by the pituitary gland, hypothalamus and ovaries. Even before the birth of a female infant who will have between 500,000 and 800,000 immature ovarian follicles in both ovaries, there is a gradual decrease in the numbers before birth up to the average age of 50 years old. The ova are the precursors of estrogen, progesterone and an ovum that has the potential to be fertilized. Following birth, the ovaries are gradually stimulated by a hormone called FSH or follicle stimulating hormone in the pituitary gland which has been stimulated by another hormone in the hypothalamus called GnRH or gonadotropin releasing hormone. When FSH stimulates the ovary there is a change in the dormant ovarian follicles to begin enlarging forming small cysts that contain estradiol. It is the estradiol that finally reaches clinical levels that will stimulate the uterine lining causing it to thicken, releases a mature ovum, and triggers a process of luteinization of the uterine lining by progesterone. This will welcome the females first menstrual period which occurs between the ages of 10 to 12 on the average. In order to understand the sequence of events that affect the clinical symptoms of either too much of certain hormones or not enough, I will walk you through the menstrual cycle from day 1 to 28.

The day the menstrual period begins there has been a decrease in estrogen, progesterone and LH (luteinizing hormone). Without support of these hormones the lining of the uterus will slough off and be accompanied by some bleeding. Immediately, since there was not a pregnancy in the uterus, the hypothalamus begins secreting FSH (follicle stimulating hormone) to start the maturation process of an egg for fertilization. This happens because of the negative feedback of low estrogen. One must understand that the sole purpose of the entire process is for procreation of the species. That is why the cessation of the menses is called menopause, i.e. the pausing of the menses. Because of the low estrogen, the levels of FSH gradually increase from the menses to reach a peak about day number 12 of the cycle. During these 12 days the immature ovum begins to enlarge enough to be seen on ultrasound as a small cystic structure and as it begins to produce estradiol. However, more than one ovum will be stimulated or matured; up to 15 or 20 follicles and sometimes even more but only one will become the “dominant follicle” that contains an ovum (egg) that can be fertilized. By the time the ovum reach about 15 to 20 millimeters in size and contains 300 to 500 pg of estrogen the estradiol will cause a release of LH from the pituitary gland which in turn will cause release of the egg from the follicle within which in resides. (See the diagram below). By the time a woman is 35 years old, up to 80% of her immature ova are depleted, a reason why there is a decreased fertility after age 35 and becomes very difficult by age 45 since most of the ova are depleted or in many cases are defined as “too old” which merely means that they likely have undergone some genetic changes that prohibit fertilization.

At the time of egg release, the FSH begins to gradually decline and the LH prevails to assist in maintaining an embryo should fertilization have occurred. But, equally and likely more important the follicle cyst that released the egg is converted into a “corpus luteum” meaning that it now produces, besides estrogen, a very important hormone, progesterone. It is progesterone that will support the fertilized egg by keeping the uterine lining thick, rich in blood and nutrients that are transferred to the early placenta. Should the egg not be fertilized in the fallopian tube on its way to the uterus, then the levels of estrogen, progesterone and LH will gradually decrease and the menses will begin because of lack of support from these hormones. This part of the menstrual cycle is an average of 14 days as is the first part of the ovulation cycle also about 14 days. Should the levels of progesterone be very low, what is now called the “luteal phase” this not only doesn’t support the pregnancy and can lead to a miscarriage but also will create “estrogen dominance” with a multiple number of symptoms, the most common known as Premenstrual Syndrome. This is associated with pre menstrual tension, bloating, weight gain, mood swings, irritability and depression, all to varying degrees. Some women will have symptoms at the time of ovulation, 4-5 days of so before the menses or sometime the entire 14 days and even during the first 2-3 days of the menses. A common term given to this deficiency of progesterone by infertility clinicians is “luteal phase defect”. This progesterone deficiency will also many times be associated with heavier, shorter and/or irregular cycles. A total absence of progesterone and actually be associated with no menses at all, commonly seen in patients with PCOS (polycystic ovarian syndrome). The obvious treatment for PCOS, frequent miscarriages, PMS or any other estrogen dominant condition is progesterone supplementation.

Since PCOS is an extreme deficiency of progesterone, there needs to be some discussion as to the process that is taking place. PCOS actually does not originate as an ovary problem but from “insulin resistance” The ovary is merely a target of the process. All normal ovaries also make a little bit of the androgen testosterone, a male sex hormone. The pancreas is an organ that makes the hormone insulin. High levels of insulin can also cause the ovaries to make more of the hormone testosterone which results in increase in hair, weight gain. Testosterone is converted in the fat to estrogen by the enzyme Aromatase. Many adolescents with PCOS have higher levels of the hormone insulin in their blood. Higher levels of insulin can sometimes cause patches of darkened skin on the back of your neck, under your arms, and in your groin area (inside upper thighs). With PCOS, LH levels are often high when the menstrual cycle starts, most likely a genetic trait. The levels of LH are also higher than FSH levels. Because the LH levels are already quite high, there is no LH surge. Without this LH surge, ovulation does not occur, and periods are irregular. With lower levels of FSH many follicles are stimulated but because of no LH surge they are not released but remain evident with ultrasound usually close to the capsule of the ovaries that appear to be a “ring of pearls” due to lack of release of the ovum. There also may be various degrees of PCOS but all will have to have a reverse LH/FSH ratio to substantiate the diagnosis. There are some women that are not overweight or hirsute but could have PCOS but must be documented by the labatory studies and not misdiagnosed. Also, one may seen the LH/FSH ratio to be about equal in amounts and have the symptoms of PCOS. To assume that other female members of a family have had PCOS should be considered suspect only but the deficiency of Progesterone can be documented by symptoms and history without laboratory documentation. That said, many women where it is suspected that their mothers or grandmothers have had PCOS may have had a significant progesterone deficiency instead which can be associated with infertility, miscarriages, weight gain etc.


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