Learning and gaining knowledge about the physiology and endocrinology of the menstrual cycle is a cornerstone of reproductive health. For doctors pursuing a fellowship in infertility and reproductive medicine in India, understanding this concept is essential as it forms the groundwork of infertility management and advanced reproductive treatments worldwide.
This process involves several structures in the body and is regulated by various hormones.
The menstrual cycle includes changes in the female reproductive system. While the length of the cycle may differ from person to person, it is usually around 28 days. These changes are designed to prepare the reproductive system for the possibility of pregnancy.
It should be noted that some sources define the term "menstrual cycle" specifically as the events related to the uterine cycle, which refers to the changes that occur in the uterus.
Others use the term more broadly to include both the ovarian cycle, which involves changes in the ovaries, and the uterine cycle. It is important to understand that both the ovarian and uterine cycles are connected, influence each other, and take place simultaneously. Even though the body has two ovaries, only one usually releases an egg each month.
The egg moves through the fallopian tube. If there is sperm present, fertilization may occur in the fallopian tube, and the egg may start to divide as it moves towards the uterus, where implantation may take place. If the egg is not fertilized, it starts to break down and cannot successfully implant in the uterus.
· The ovarian cycle is referred to as the inner cycle, while the uterine cycle is the outer cycle.
· The entire menstrual cycle is typically 28 days. The ovarian cycle consists of two main phases: the follicular phase and the luteal phase. The uterine cycle includes three main phases: the menstrual flow phase, the proliferative phase, and the secretory phase.
· The menstrual flow phase marks the beginning of the uterine cycle. During this time, the lining of the uterus usually sheds over about five days, although it may last longer. This process is known as menstruation or a period. Since these cycles happen at the same time, the ovarian cycle also progresses during this phase.
· The follicular phase begins with the growth of follicles in the ovaries. Each follicle contains an egg, and the follicle acts as a small container for the egg, which continues to develop throughout the phase.
During the proliferative phase, which generally starts around day 5 to 7, the uterine lining, or endometrium, starts to regrow.
This is important because the lining needs to be rich in blood vessels to support a developing blastocyst, which is an early stage of a fertilized egg that has divided several times.
We are still in the follicular phase of the ovarian cycle, but by day 5, the follicles are starting to grow and will eventually reach the surface of the ovary.
Ovulation, a key event in the ovarian cycle, typically occurs around day 14. At this point, the most developed follicle on the surface of the ovary ruptures and releases an egg. This egg then travels to the fallopian tube, where it may be fertilized by a sperm cell. During this phase, the other follicles usually shrink, and their eggs are lost. However, there are many eggs available for the next cycle.
After ovulation, the ovarian cycle moves into the luteal phase. The ruptured follicle, now called the corpus luteum, remains in the ovary and continues to function by producing hormones that help build and prepare the uterine lining for potential implantation. The uterine lining continues to develop and become ready for the possible implantation of a blastocyst.
If implantation does not occur, the corpus luteum will eventually break down, leading to the degeneration of the uterine lining. A new menstrual cycle begins when bleeding resumes.
But what about the control of all of this? The regulation? We're going to first introduce the hormones and glands that regulate those cycles, and then walk through the cycles again and explain how those hormones regulate each phase. So to introduce the glands and hormones, you've got the gland called the hypothalamus.
The hypothalamus releases GnRH, or a gonadotropin-releasing hormone. The main function of GnRH? GnRH stimulates another gland known as the anterior pituitary. The anterior pituitary is a gland that releases FSH, follicle-stimulating hormone, and LH, luteinizing hormone.
For females, FSH has a major role in stimulating follicles, so it helps them grow. The other hormone, LH, also helps with this, but it's also critical in starting ovulation, which releases the egg, and it also helps the ovaries with their work of making hormones. Finally, the ovaries themselves are glands that secrete hormones, progesterone and estradiol, which is a form of estrogen, are two ovarian hormones that will have major roles in the menstrual cycle, which we'll get to very soon.
Back to day 1, uterine cycle, we're in the menstrual flow phase. After the corpus luteum broke down, estradiol and progesterone levels dropped, and this hormone drop can lead to blood vessels in the uterine lining to constrict, which cuts off circulation to the uterine lining and contributes to the breakdown of the uterine lining. This results in bleeding, or menses. Now meanwhile, let's consider the ovarian cycle. Follicular phase, early on in the follicular phase, the hypothalamus will be secreting GnRH, which stimulates the anterior pituitary to release FSH and LH, though in low amounts.
Small follicles have FSH receptors, FSH will stimulate the growth of the follicles. As these follicles grow, they begin to release estradiol. Low levels of estradiol will result in negative feedback on the hypothalamus and anterior pituitary, which inhibits the secretion of GnRH and keeps levels of LH and FSH relatively low. Back to the ovarian cycle, still in the follicular phase, though later in the follicular phase, the low FSH levels prevented most follicles from reaching this point. But there will be a mature follicle that is dominant in making more and more estradiol. Now it gets tricky here, so hang with me. While you remember low levels of estradiol inhibiting the hypothalamus and anterior pituitary, ultimately leading to low secretion of GnRH, FSH, and LH, high levels of estradiol actually stimulate these glands, resulting in more GnRH secretion through positive feedback.
So when that estradiol reaches a certain high level, GnRH secretion will go up and is expected that with that, the anterior pituitary will start cranking out more FSH and LH. LH starts to really increase. This rapid increase is known as an LH surge. The LH surge will trigger ovulation to happen roughly a day or so later. Recall that ovulation is when there is a bursting of that mature dominant follicle releasing the egg. The ovarian cycle moves to the luteal phase after ovulation.
LH is involved in stimulating that follicle that had burst to become the corpus luteum. Now, we had mentioned the corpus luteum has a job helping the uterine lining build up as it prepares for potential implantation, and it does as the corpus luteum produces estradiol and progesterone, which are important for the next uterine cycle phase. That next phase of the uterine cycle is the secretory phase, where both estradiol and progesterone, especially progesterone, are responsible for helping to build up and maintain the uterine lining.
In addition, that estradiol and progesterone, the combination of the two, will inhibit the hypothalamus and anterior pituitary through negative feedback, which ultimately means less GnRH, FSH, and LH will be secreted. That's important because there could, after all, be a potential pregnancy and so more follicles do not need to be developed right now. Now, if there is no implantation of a blastocyst in the uterus, let's look at the end of the ovarian cycle in the luteal phase.
The corpus luteum breaks down. If it breaks down, it's not going to be making all the estradiol and progesterone. Those hormone levels drop significantly, which will stop the building of the uterine lining, that endometrium.
What does that lead to?
Surprise! It's back to day 1 in the menstrual flow phase of the uterine cycle and the endometrium begins to shed. With the drop of both estradiol and progesterone, that negative feedback is gradually lifted, so now the hypothalamus can resume GnRH secretion as the cycle starts anew.
When the estradiol reaches a certain level, it results in FSH and LH rising. When estradiol peaks, it leads to an LH surge. That LH surge triggers ovulation roughly a day or so later. Then, after ovulation, that ruptured follicle becomes the corpus luteum, and the corpus luteum will soon start to secrete estradiol and progesterone. If no implantation of a blastocyst in the uterus happens, that corpus luteum will ultimately break down. The hormone levels plummet, we could start again.
So now one question you might have, what if a blastocyst did implant? Would all this still start over? No, because if pregnancy occurred, that uterine lining would need to be maintained and not shed. It's important for the developing embryo, and the body also would not release more eggs at the same time when there's already a pregnancy. Instead, the blastocyst will start releasing HCG. HCG is a major hormone that many pregnancy tests will use to detect a pregnancy. HCG will be involved in stimulating the corpus luteum to remain active, and that is important because the progesterone that the corpus luteum secretes is especially critical for maintaining that uterine lining. Eventually, the placenta will take over with secreting hormones and the corpus luteum will no longer be needed.
Not only are these intricate alterations in the ovarian and uterine cycles intriguing from a biological standpoint, but they also have important therapeutic implications. In fact, a thorough understanding of these systems is essential for identifying and treating a variety of reproductive issues for physicians pursuing a fellowship in reproductive medicine in Bangalore.
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