Abstract
The female reproductive system experiences regular cyclical alterations referred to as the menstrual cycle. This is in contrast to the male reproductive system. This cycle functions as the body’s systematic preparation for ovulation, and ensures that if fertilisation takes place, the uterine lining is thick enough for the implantation of the fetus to take place successfully. This article aims to provide a detailed explanation of the four phases of the menstrual cycle; this includes a comprehensive overview of mensuration, the follicular and proliferative phase, ovulation, and the luteal and secretory phase. The description of the aforementioned will be in accordance with the ovarian and endometrial cycles.
Introduction
The menstrual cycle is a physiological process that prepares the female body for ovulation and the possibility of pregnancy. Hormones released by the hypothalamus and pituitary gland (f, mainly the follicle stimulating hormone (FSH) and luteinizing hormone (LH)) facilitate the development of ovarian follicles and initiate ovulation. Hormones produced by the ovaries i.e. oestrogen and progesterone etc condition the cervix to permit sperm entry into the endometrial cavity. Additionally, they are also responsible for promoting the growth and maturation of the endometrium in anticipation of a fertilised ovum’s implantation. In the absence of pregnancy, the cycle resets[1][2]. The uterine lining is lost through the vagina - this event is menstruation. It is essential for the uterine outflow tract, which includes the cervix and vagina, to remain open to facilitate the expulsion of menstrual fluid at the end of each cycle[1].
The regulation of the menstrual cycle involves a sophisticated interplay among the hypothalamus, ovaries, uterus, and anterior pituitary gland. The typical duration of the menstrual cycle is approximately 28 days, although it can vary between 25 and 32 days. The most significant fluctuations in cycle length are observed during the years following the onset of menarche, which marks the beginning of menstruation, and prior to menopause, the phase when menstruation stops, typically occurring around the age of 51[3].
The menstrual cycle consists of two interrelated cycles: one occurring in the ovaries known as the ovarian cycle, and the other in the endometrium called the endometrial cycle[1]. The endometrium is the lining of the uterus and plays an instrumental role involving the preparation for implantation, the sustenance of pregnancy should implantation take place, and the occurrence of mensuration in the absence of fertilisation[4]. The ovarian cycle is divided into three phases. They are the follicular phase, ovulation, and luteal phase. Conversely, the endometrial cycle includes the proliferative phase, the secretory phase, and the menstrual phase. Typically, the ovarian follicular phase aligns with the menstrual and proliferative phases occurring in the endometrium, while the luteal phase of the ovarian cycle corresponds to the secretory phase of the endometrial cycle[1].
Phase 1 - Mensuration
The uterus consists of the three following layers:
Endometrium - this lines the lumen
Myometrium - this is a layer of visceral muscle located directly beneath the endometrium
Perimetrium - this is a serous membrane that faces the abdominal cavity
The endometrium in particular experiences significant changes in response to the monthly hormonal cycle and is expelled from the body during menstruation. It is further categorised into a functional layer known as the stratum functionalis. This is oriented towards the lumen of the uterus. The endometrium is also composed of a basal layer referred to as the stratum basalis which is located beneath the stratum functionalis[5].
The sharp decrease in the concentrations of progesterone and estradiol, another hormone produced by the ovaries, at the end of the luteal phase initiates the shedding of the endometrium as it can no longer be maintained in the absence of these chemical messengers. This process is known as menses. The onset of menstrual bleeding is marked as the first day of the menstrual cycle. Menstruation occurs during the early days of the follicular phase; this statement establishes the correlation between the ovarian and endometrial cycle. Furthermore, the length of menses can vary, but it typically lasts up to 8 days maximum[1]. The main constituents in menstrual fluid are blood, endometrial cells, vaginal secretions, and various biochemical substances like cytokines[1][5].
At the commencement of the menstrual cycle, the levels of estrogen and progesterone are at their lowest. During menstruation, the uterus is stripped of the stratum functionalis and a significant portion of the stratum basalis. Nevertheless, even as the endometrium is being shed, cellular proliferation from the neighbouring cervix, the fallopian uterotubal junction, and the glandular cells situated deep within the stratum basalis, initiate the restoration of the endometrial lining which leads to the next phase[5].
Phase 2 - Follicular and Proliferative Phase
The follicular phase of the menstrual cycle is characterised by the development of ovarian follicles that are being prepared for ovulation. Concurrently, the endometrium undergoes changes, resulting in the designation of the follicular phase as the proliferative phase[6].
Follicular Phase
As the previous menstrual cycle concludes and the corpus luteum disintegrates, there is a decline in the levels of estrogen, progesterone, and inhibin A. This sequence of events initiates positive feedback to the hypothalamus and anterior pituitary, resulting in a pulsatile release of gonadotropin-releasing hormone (GnRH) and follicle-stimulating hormone (FSH) into the bloodstream[7]. The elevation of FSH promotes the activity of granulosa cells in the ovaries, leading to the recruitment of multiple follicles from each ovary. Although several follicles mature, only one Graafian follicle will be released during that cycle.
The mid-follicular phase is characterized by an increase in oestrogen, especially estradiol, and inhibin B levels, which are produced by the ovarian follicles in reaction to elevated FSH levels. This increase triggers a negative feedback mechanism that results in a reduction of FSH levels. Throughout this phase, the process of selecting the follicle that will ultimately undergo ovulation takes place, and this selected follicle is referred to as the dominant follicle. The inhibition of FSH secretion signals the end of the follicular phase[6][7].
Proliferative Phase
In addition to the maturation of ovarian follicles, the endometrium experiences considerable changes during the initial 14 days of the menstrual cycle. Consequently, this timeframe is categorised as the proliferative phase. The rising levels of estradiol play a crucial role in driving these endometrial modifications that take place prior to ovulation. The proliferative phase can be subdivided into early, mid and late stages; each of these are characterised by distinct features that are outlined below[6][8].
Early proliferative phase: This stage commences shortly after menstruation, generally occurring between days 4 and day 7. During this period, the regenerating endometrium develops a thin, linear, and echogenic layer. The glands are short, straight and narrow with the emergence of microvilli and cilia on the epithelial cells. Some inactive glands, still in the process of recovery from the preceding menstrual cycle, may present as cuboidal and irregular.
Mid-proliferative phase: The endometrium advances to this phase typically around day 8 to 10 of the cycle. During this, the glands become more elongated and curved and become lined with columnar epithelium.
Late proliferative phase: This phase spans from approximately day 11 to 14. Developments in this period include the glands becoming coiled and densely packed while they are actively undergoing mitosis and nuclear pseudostratification. The stratum functional layer, also referred to as the inner lining of the endometrium, reaches its peak thickness. This can range from 0.5 to 5.0mm and it exhibits a trilaminar structure[6].
Phase 3 - Ovulation
Ovulation is a physiological event characterised by the rupture and subsequent release of the dominant follicle from the ovary into the fallopian tube, where it may potentially be fertilised. This process is governed by fluctuating levels of gonadotropic hormones, specifically FSH and LH[9]. Typically, ovulation occurs at day 14 prior to the onset of menstruation but fluctuation in dates can take place. During the follicular phase, levels of estradiol increase and towards the conclusion of it, 17-β estradiol transitions from exerting negative feedback to providing positive feedback at the anterior pituitary gland[1].
The precise regulation and controlled fluctuations of the hormones involved are crucial for the maturation and release of an oocyte; this is a cell in the ovary capable of undergoing meiotic division to form an ovum. Key hormones in the ovulation process include gonadotropin-releasing hormone (GnRH), a peptide hormone produced and secreted by the hypothalamus. GnRH acts as a releasing hormone that prompts the anterior pituitary gland to secrete FSH and LH, with variations in the frequency of GnRH pulses determining the specific hormone released. Low-frequency pulses of GnRH lead to the secretion of FSH, while high-frequency pulses result in the release of LH. During the follicular phase of the uterine cycle, the secretion of estrogen stimulates the granulosa cells to autonomously enhance their own estrogen production, contributing to elevated serum estrogen levels. This increase is detected to the hypothalamus, which in turn raises the frequency of GnRH pulses, ultimately triggering the LH surge that induces follicular rupture and the release of the oocyte from the corpus luteum, alongside the luteinization of granulosa cells that facilitates the synthesis of progesterone in place of estrogen[9].
Phase 4 - Luteal and Secretory Phase
The luteal phase and the secretory phase represent two concurrent stages of the menstrual cycle, involving both the corpus luteum and the endometrium. The luteal phase, a component of the ovarian cycle, follows the ovulation of an egg. In this phase, the corpus luteum synthesises progesterone and oestrogen. Progesterone plays a crucial role in thickening the uterine lining, thereby preparing the uterus for the potential implantation of a fertilised egg. Simultaneously, the secretory phase, which is part of the endometrial cycle, occurs parallel to the luteal phase. During this, the endometrium releases a clear fluid[10]. Both initiate with ovulation and conclude with the onset of menstrual bleeding. In contrast to the variable duration of the follicular or proliferative phase, the luteal or secretory phase is relatively stable for each individual, generally lasting around 14 days.
During this phase, progesterone serves as the predominant hormone, stimulated by luteinizing hormone (LH). Progesterone facilitates the maturation of the endometrium, preparing it for the possible implantation of a fertilized ovum. It encourages the formation of intricate glands, enhances glycogen storage for energy, and increases the surface area of the spiral arteries. Furthermore, progesterone thickens and reduces the elasticity of cervical mucus, thereby impeding sperm passage. It also results in a slight elevation of basal body temperature.
In the event of fertilization, the ovum secretes human chorionic gonadotropin (hCG), which prompts the corpus luteum to sustain progesterone production. Conversely, in the absence of fertilization, the natural increase in progesterone inhibits LH release through negative feedback at the pituitary gland, leading to a swift decrease in both progesterone and estradiol levels as the phase concludes. As these hormone levels diminish, the hypothalamus releases gonadotropin-releasing hormone (GnRH) from its feedback inhibition, resulting in an increase in secretion in anticipation of the next cycle[1].
Conclusion
The menstrual cycle plays a crucial role in the health and well-being of women, Variations in menstrual cycles may result from fluctuations in the concentrations of hormones that are secreted during either the ovarian or endometrial cycles. Furthermore, these can be linked to various medical conditions like metabolic syndrome, coronary heart disease (CHD), and diabetes type II. Timely diagnosis and intervention can mitigate the risk of infertility and other health issues. Given the limited literature available on this subject, it is essential to pursue further research in this area.
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