Human Female Hormonal System

The normal reproductive years of the female are characterized by monthly rhythmical changes in the values of secretion of the releted hormones and equivalent physical changes in the ovaries and other sexual organs. This rhythmical pattern is called the female monthly sexual cycle (or, the menstrual cycle). The duration of the cycle averages 28 days. It may be as short as 20 days or as long as 45 days in some women, although abnormal cycle length is frequently related with decreased fertility.
There are mainly two important results of the female sexual cycle.

1.      Only a single ovum is normally released from the ovaries each month, so normally only a single fetus will begin to grow at a time based on fertilization.

2.      The uterine endometrium is prepared in advance for implantation of the fertilized ovum at the necessary time of the month. 

There are four phases to complete a full hormonal regulation. These are: 

1.      Follicular Phase

2.      Ovulation

3.      Luteum Phase

4.      Menstruation

Gonadotropic Hormones and Their Effects on the Ovaries:

The ovarian changes that occur during the menstrual cycle depend completely on the gonadotropic hormones FSH and LH, secreted by the anterior pituitary gland. Absence of these hormones, the ovaries still remain inactive, which is the case throughout childhood, when almost no pituitary gonadotropic hormones are secreted. The pituitary begins to secrete progressively more FSH and LH at the age 9 to 12 years, which leads to onset of normal monthly menstrual cycles beginning between the ages of 11 and 15 years. This period of the change is called puberty, the time of the first menstrual cycle is called menarche. Both FSH and LH are stimulate their ovarian target cells by linking with highly specific FSH and LH receptors in the ovarian target cell membranes. In turn, the activated receptors raise the cells’ rates of secretion and normally the growth and proliferation of the cells as well.

Figure: Regulation of the hypothalamic-pituitary ovarian axis in females. Stimulatory effects are shown by (+)and

negative feedback inhibitory effects are shown by (-). For large view Please click here

Follicular Phase:

A newly born female child, each ovum is surrounded by a single layer of granulosa cells; the ovum, with this granulosa cell scabbard, is called a primordial follicle. Throughout childhood, the granulosa cells are provide nutrition for the ovum. Then, after getting puberty, when FSH and LH release from the anterior pituitary gland, some of the follicles among them begin to grow, its called primary follicles. At puberty only 60000 to 80000 primary follicles are left in each ovary.

Development Follicles

During the first few days of each monthly female sexual cycle, the concentrations of both FSH and LH increase mini to moderately, FSH increase little bit greater than that of LH. These hormones, specially FSH, cause accelerated growth of 6 to 12 primary follicles in every month. The primary follicles get surrounded by more layers of granulosa cells and a new theca, called secondary follicles. The secondary follicle soon transforms into a tertiary follicle which is characterized by a fluid filled cavity called antrum. The theca layer is organized into 2 theca, one is  an inner theca interna and another is an outer theca externa.

Figure: Stage of follicular growth in the ovary, also presenting the formation of the corpus luteum after ovulation.

After the early proliferative phase of growth, extended for a few days, the mass of granulosa cells secretes a follicular fluid what contains a high concentration of estrogen, one of the significant female sex hormones.

Once the antral follicles(A developing stage of follicle) begin to grow, their growth occurs almost explosively. The ovum, itself also enlarges in diameter another threefold to fourfold, a total ovum diameter increase up to 10 fold, or a mass increase of 1000 fold. As the follicle enlarges, the ovum still remains set in a mass of granulosa cells located at one pole of the follicle.

Only One Follicle Fully Matures Each Month, and the Remainder Undergo Atresia (the rest 5 to 11 ovarian follicles which do not ovulate during the menstrual cycle) The single follicle reaches a diameter almost 1 to 1.5 cm at the time of ovulation and is called the mature follicle.

Ovulation:

In a woman who has a normal 28 days female sexual cycle, ovulation fall out 14 days after the onset of menstruation.  Surge of  LH is necessary for final follicular growth and ovulation. Without LH, even when large quantities of FSH are available, the follicle will not develop to the stage of ovulation. About 2 days before ovulation, the rate of LH secretion by the anterior pituitary gland increases notably, rising 6 fold to 10 fold and before ovulation peaking about 16 hours. FSH also increases about twofold to threefold at the same time, and the FSH and LH act exaggeratingly to cause rapid swelling of the follicle during the last few days before ovulation. While progesterone begin to be secreted of increasing amounts. On the granulosa and theca cells, the LH also has a specific effect to conver them mainly to progesterone-secreting cells. Therefore, the rate of estrogen secretion begins to fall about 1 day before ovulation. Within a few hours, two events occur

1.      Swelling of the entire follicle

2.      Growth of new blood vessels into the follicle wall

Finally, the combination of above 2 the follicle be ruptured, with discharge of the ovum.

Luteum Phase:

During the first few hours after discharge of the ovum from the follicle, the remaining granulosa and theca interna cells change rapidly into lutein cells. They enlarge in diameter two or more times and become filled with lipid inclusions that give them a yellowish (LH responsible for this) appearance. This method is called Latinization, and the total amount of cells together is called the corpus luteum. In the corpus luteum the granulosa cells  develop extensive intracellular smooth endoplasmic reticula that form large amounts of estrogen and progesterone (more progesterone than estrogen during the luteal phase). The corpus luteum normally grows to about 1.5 cm in diameter, reaching this stage of development 7 to 8 days after ovulation. Then it begins to involute and ultimately miss out its secretory function, lipid characteristic and its yellowish about 12 days after ovulation, becoming the corpus albicans which absorber over the months. Once LH has acted on the granulosa and the newly formed lutein cells seem to be programmed to go through a preordained sequence of 1. proliferation, 2. enlargement 3. secretion and  then 4. degeneration. All this occurs in about the 12 days.

During the luteal phase the estrogen and progesterone to a lesser extent, secreted by the corpus luteum.  Final involution of carpus luteum normally happens at the end of almost exactly 12 days of corpus luteum life, which is around the 26th day of the normal female sexual cycle that means 2 days before menstruation begins.  At this time, the sudden stop of secretion of estrogen, progesterone, and inhibin by the corpus luteum removes the feedback inhibition of the anterior pituitary gland, permitting it to secret  increasing amounts of FSH and LH again. Beginning a new ovarian cycle, FSH and LH initiate the growth of the new follicles. The secretion of progesterone and estrogen at this time also leads to menstruation by the uterus.

Monthly Endometrial Cycle and Menstruation

Associated with the monthly cyclical production of estrogens and progesterone by the ovaries is an endometrial cycle in the lining of the uterus that operates through the following stages:

1.      Proliferation of the uterine endometrium;

2.      Development of secretory changes in the endometrium; and

3.      Desquamation of the endometrium, which is known as menstruation.

Figure: Phases of endometrial growth and during each month human female sexual cycle

Proliferative Phase:  It’s also called the Estrogen Phase of the Endometrial Cycle, happen before vulation. At the beginning of each monthly cycle, most of the endometrium has been come off by menstruation. After menstruation, only a thin layer of endometrial stroma and epithelial cell remains. Under the influence of estrogens, secreted in increasing quantities by the ovary at the initial time of monthly sexual circle. After begening of menstruation the endometrial surface is re-epithelialized within 4 to 7 days. Then, during the next week and a half, before ovulation occurs, the endometrium increases greatly in thickness by 3 to 5 mm owing to increasing numbers of stromal cells and

Development of secretory changes: It is known as Progestational Phase of the Endometrial Cycle, happen after ovulation. This is mainly endometrial building phase. About a week after ovulation, the endometrium has a thickness of 5 to 6 mm. The purpose of endometrial changes is to produce a secretory endometrium that contains large amounts of stored nutrients to provide appropriate conditions for implantation of a fertilized ovum. A ovum can be fertilized after 3 to 4 days of ovulation. A fertilized ovum enters the uterine cavity from the fallopian tub. Until the ovum implants (7 to 9 days after ovulation), the uterine secretions (uterine milk), provide nutrition for the early dividing ovum. Then, once the ovum implants in the endometrium, as a result making great quantities of nutrients available to the early implanting embryo.

Menstruation: If the ovum is not fertilized after 3 to 4 days of ovulation, the corpus luteum in the ovary suddenly involutes and decrease estrogens and progesterone to low levels of secretion. End of monthly sexual circle these 2 hormones, especially progesterone reduction is the main cause of menstruation. Sudden decoration of these 2 hormones decrease the stimulation of endometrial cell then reduce almost 65 percent of its previous thickness. Gradually, the necrotic outer layers of the endometrium separate from the uterus at the sites of the bleedings until, about 48 hours after starting menstruation. Once only endometrial stroma and epithelial cells that are remains and all acting together, initiate uterine contractions that expel the uterine contents. During normal menstruation, approx 40 ml of blood and an additional 35 ml of serous fluid are lost. Menstruation remain up to 4 to 7 days after starts, by this time the endometrium has become re- epithelialized.

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