The Female Cycle Explained

The female cycle (synonyms: menstrual cycle; monthly cycle) is a complex event that repeats itself in a regular rhythm from the day of menarche (a woman’s first menstrual period), which occurs around the age of 13, until menopause (a woman’s last menstrual period). In advance, brief remarks on the development of puberty:

  • Pubarche (pubic hair) is the first sign of puberty in girls (at about 10, 5 years (in 85% of cases); range of variation: 8-13 years).
  • Thelarche (breast development; Tanner stage B2) begins at 10.5 years (9-14 years); occurrence before the completed 8th year is considered premature
  • Menarche (first appearance of menstruation at puberty) begins approximately 2-2.5 years after thelarche, i.e. at 13.0 years (11.5-15 years; see also below)
  • Pubertal growth spurt begins in girls at about 12 years of age.

Pubertas praecox (premature puberty) is spoken of in girls when the onset of puberty occurs before the 8th birthday. In this case, the course shows accelerated growth, acceleration (“acceleration”) of bone maturation and uterine length > 3.5 cm.With prenatal paracetamol exposure for more than 12 weeks, girls may experience an earlier onset of puberty (1, 5 to 3 months earlier). Note: Girls with idiopathic pubertas praecox achieve normal adult body size when therapy with a GnRH analogue (drugs used to artificially lower testosterone or estrogen levels in the blood) is started early.

Anatomy

Uterus (Womb) The uterus (womb) is a hollow muscular organ about 6-7 cm long, 4-5 cm wide, and weighing 50-100 g. However, significant variations can occur. Size and weight can increase significantly, especially after pregnancies. The uterus has the shape of an upside-down pear. It consists of the cervix uteri (cervix; this is where the cancer screening smear is taken) and the corpus uteri (body of the uterus). The surface of the cervix uteri visible in the vagina (vagina) is called the portio (transition from the cervix uteri to the vagina (vagina)). From the dome, called the fundus, go the two tubes (fallopian tubes). The uterus is the incubation space for pregnancies. If pregnancy does not occur after ovulation, the endometrium (lining of the uterus) prepared for pregnancy is shed with menstrual bleeding to be rebuilt in a new cycle. Tube (Fallopian tubes) The fallopian tubes (singular: Latin tuba uterina, tuba fallopii; Greek salpinx; also oviduct) originate in pairs from the fundus of the uterus and extend with a length of 10-15 cm in the direction of the two ovaries. They are muscular tubes lined with mucosa, which serve to transport the cracked egg (oocyte) into the uterus. At the lateral (far from the uterus) end, there are fringe-shaped extensions (fimbrial funnels) that overlie the egg ready to jump at the site of ovulation of the ovary (ovary) and guide it into the fallopian tube by sucking contractions. Tubal gravidities (tubal pregnancies) can occur if the tubes are defective, for example, due to inflammation. Ovary (ovary)

The ovaries are responsible for the production of eggs (oocytes) and the production of female sex hormones (estrogens, progestins). They are the counterpart of the male testicles. The color is white and the shape is almond-shaped. The ovaries are about 3-5 cm long and 0.5-1 cm thick. They consist of cortex and the medulla, covered by a single-layer epithelium. The cortex contains the oocytes at different stages of development. The medulla consists of connective tissue and contains blood and lymphatic vessels, as well as nerves. During sexual maturity, the follicles (“egg follicles”) located in the cortex are stimulated to grow and produce hormones.

Endocrinology of the menstrual cycle

The menstrual cycle is shaped by the functional interaction of hormones at the hypothalamic-pituitary-ovarian (diencephalic-pituitary-ovarian) level:

  • Hypothalamus – The hypothalamus is part of the diencephalon (interbrain) and, as the supreme control center of autonomic body functions, has the task of controlling circulation, respiration, fluid or food intake, and sexual behavior. For this purpose, this secretes a variety of hormones, of which the gonadotropin-releasing hormone (GnRH) has an influence on the menstrual cycle.
  • Pituitary Gland – The pituitary gland (pituitary gland) is directly controlled by the hypothalamus and secretes luteinizing hormone (LH – yellowing hormone from Latin luteus) and follicle stimulating hormone (FSH).
  • Ovarian hormones – Here are mainly the hormones estradiol (main estrogen) and progesterone (progestogens).

To understand the cycle, knowledge of the functions of each hormone is very important. These are briefly described below:

  • FSH – Follicle-stimulating hormone (also called follitropin) is a hormone that, with the cooperation of luteinizing hormone (LH), controls follicle maturation (egg maturation) and estrogen formation in women.
  • LH – Luteinizing hormone (LH or also called lutropin) is a hormone from the pituitary gland (pituitary gland), which controls follicle maturation (egg maturation) and ovulation (ovulation) in women with the cooperation of follicle-stimulating hormone (FSH). It is also involved in estrogen and progesterone synthesis (production of estrogens and progesterone).
  • Estrogens – Estrogens promote the formation of secondary sexual characteristics such as breast growth and the characteristic female fat distribution. In cooperation with androgens (the male hormones) pubic hair (pubarche) develops. Estrogens have a growth-promoting effect on the cells of the vagina (vagina) and are responsible for the formation of the vaginal flora (Döderlein flora). In the uterus, the female hormone promotes the formation of the endometrium (lining of the uterus) and is indirectly involved in follicle maturation (egg maturation) in the ovaries. Estradiol (E2) is a form of the female sex hormone. It is produced primarily in the ovaries (Graafian follicle, corpus luteum) in women and in the placenta (placenta) in pregnant women. The concentration of estradiol changes during the female cycle.
  • Progesterone (corpus luteum hormone) – Progesterone is a hormone from the group of progestins. It is produced in the ovaries in the corpus luteum (in the corpus luteum) and increases in the luteal phase (corpus luteum phase) – on the 5th-8th day after ovulation (ovulation) the maximum progesterone serum level is reached – and in pregnancy. Progesterone is responsible for nidation (implantation of the fertilized egg) and also serves to maintain pregnancy. It is stimulated for release by luteinizing hormone (LH). Progesterone shows a cycle-dependent rhythm with an increase in concentration during the luteal phase.

The menstrual cycle serves evolutionary biology of the recurrent possibility of fertilization or the emergence of pregnancy (conception; conception) through the development of a mature oocyte (egg), which implants in the prepared endometrium (endometrium) of the uterus (uterine). The implantation of the oocyte into the endometrium is called nidation. The oocytes of the woman have already undergone the first developmental steps during oogenesis (egg development), which takes place during embryonic development. During puberty (the first visible sign of puberty is thelarche (breast development), which begins between the ages of 9 and 12; pubarche (beginning of pubic hair development) begins between the ages of 10 and 12; approx. one year after the first signs of puberty become visible, a growth spurt begins; menarche (first menstrual period) occurs at the age of 11 to 14 years; the growth spurt is completed at about 18 years) or cell division is completed during fertilization. Study results on menarche age show,

  • that early menarche (early period; <11 years of age) and childlessness are associated with a high risk of premature menopause (last menstrual period before 40 years of age) or early menopause (last menstrual period between 40 to 44 years of age):
    • 1.8-fold risk of premature menopause and 1.31-fold risk of early menopause.
    • Childless women versus women with two or more children: 2.26-fold risk for premature menopause and 1.32-fold risk for early menopause
    • Childless women with early menarche: 5.64-fold risk for premature menopause and 2.16-fold risk for early menopause
  • That prenatal smoke exposure (tobacco use) and low birth weight increase the likelihood of earlier menarche.
  • That increased consumption of sugary beverages is associated with metabolic changes that are also likely to influence the timing of menarche. Increased consumption of these beverages is predictive (“predictive”) of early menarche, without this consumption being associated with increased BMI (body mass index).

The female cycle has a duration of about 28 days, with the beginning seen on the first day of menstruation. A distinction is made between a cycle of the ovary (= ovarian cycle) and a cycle of the endometrium (= endometrial cycle).

Ovarian cycle

The ovarian cycle is controlled by the gonadotropin hormones of the anterior pituitary (front lobe of the pituitary gland) and by the ovary itself and consists of four phases:

  • Follicular phase (1st half of the cycle).
  • Ovulation (ovulation)
  • Luteal phase (2nd half of the cycle)
  • Menstruation (monthly bleeding)

The cycle length is between 25 and 35 days (= eumenorrhea), with an individual variation of no more than 2 to 3 days from cycle to cycle. The bleeding period is about 5 to 7 days. Follicular phase (egg maturation phase; beginning of the 1st half of the cycle) – The follicular phase is dominated by high FSH blood levels. The hormone stimulates the so-called dominant follicle (a follicle that is most advanced in its development, also called an egg follicle) and promotes its increased growth. This follicle inhibits the growth of the other underdeveloped follicles, whereupon they degenerate. The cells that form the follicle (granulosa cells* ) are also stimulated and start producing estrogen, which in the sense of a negative feedback (feedback) suppresses the further release of FSH in the pituitary gland. * Granulosa cells (lat. granum “grain”; “granule cells”) are epithelial cells in the ovarian follicles (ovarian follicles). They develop under the influence of gonadotropins (FSH, LH) during follicle maturation (egg maturation) from the follicular epithelial cells of the primary follicle, which thereby becomes the secondary follicle. In the mature tertiary follicle (diameter approximately 10 mm), they form the inner layer of the follicle wall and grow into the “egg mound” (cumulus oophorus), to which the oocyte (egg cell) adheres. The granulosa cells secrete (excrete) the follicular fluid, which then fills the follicular cavity. After ovulation (ovulation; follicle rupture), the oocyte is surrounded by a layer of granulosa cells called the corona radiata, which is adjacent to the zona pellucida (glass skin; protective covering around the oocyte). The granulosa cells remaining in the ovary (ovary) deposit lipids (luteinization; corpus luteum formation) and become the granulosalutein cells of the corpus luteum (corpus luteum). Ovulation (ovulation) – Ovulation occurs on the 13th-15th day of the cycle. For this purpose, the tertiary follicle (see above) has developed further and the follicular cavity, which is now full of follicular fluid, jumps. It is now called a Graaf follicle or a tertiary follicle ready to jump. Hormonally, the following takes place: Estrogen production increases as the follicle grows. When estrogen concentration exceeds a threshold, positive feedback occurs and the release of LH is stimulated, which causes ovulation (ovulation). LH also induces the formation of the corpus luteum (corpus luteum) and the conversion of granulosa cell production to progesterone. This process is called luteinization (corpus luteum formation). According to a study that analyzed data from 124,648 women from Sweden, the U.S. and the U.K., the average follicular phase lasts 16.9 days (95% confidence interval: 10-30) and the average luteal phase lasts 12.4 days (95% CI: 7-17). Thus, ovulation does not always occur on day 14. Depending on the cycle length, the follicular phase length varies:

  • Cycle length 25-30 days: 15.2 days (average follicular phase length).
  • Cycle length 21-24 days: 10.4 days
  • Cycle length 31-35 days: 19.5 days
  • Cycle length 36-35 days: 26.8 days

Furthermore, age, a factor known for a long time, and body weight affect the cycle. Luteal phase (corpus luteum phase; 2nd half of the cycle) – After ovulation (ovulation), the corpus luteum (corpus luteum) is formed from the follicle.Under the influence of LH, the luteal cells produce the progestogen progesterone, which prepares the uterus for nidation (implantation of the fertilized egg). Furthermore, the progesterone leads to an increase in body temperature (of 0.3 °C or more); in this context, one speaks of a hyperthermic phase. During the daily measurement of the basal body temperature (measurement of the body temperature before getting up), the luteal phase is visible in the basal body temperature curve (BTK) as a hyperthermic phase. If no implantation (“implantation”) of an egg takes place, the regression of the corpus luteum, the so-called luteolysis, occurs on about the 25th-26th day of the female cycle. This is followed by the shedding of the endometrium (lining of the uterus), called desquamation, and menstruation begins. A normal menstruation (monthly bleeding) lasts about four days and repeats in a cycle of 28 days each. Cycle disorders or bleeding abnormalities (bleeding disorders) are divided into rhythm disorders and type disorders – see cycle disorders for more information.

Endometrial cycle (endometrial cycle)

The cycle begins with the first day of menstrual bleeding and ends with the first day of the next bleeding. Based on a 28-day cycle, a distinction is made between 2, 3 or 4 phases, taking into account the changes in the endometrium (lining of the uterus): Two-phase model:

  • Phase 1: proliferation phase = follicular phase (1st-14th day of the cycle) (regeneration of the mucosa) = phase before ovulation (ovulation).
  • Phase 2: Secretory phase = luteal phase (15th-28th day of the cycle) (preparation for nidation (implantation) of the fertilized egg) = phase after ovulation (ovulation). It is characterized by further growth and storage of glycogen in the mucosa in preparation for the supply of the nidating egg.

Three-phase model:

  • Phase 1: Desquamation phase (menstruation-bleeding phase) (1st-4th day of cycle).
  • Phase 2: Proliferation phase (5th-14th day of the cycle).
  • Phase 3: Secretion phase (15.-28. cycle day).

Four-phase model:

  • Phase 1: Desquamation phase (menstruation-bleeding phase) (1st-4th day of cycle).
  • Phase 2: Proliferation phase (5th-14th day of the cycle).
  • Phase 3: Secretion phase (15.-24 cycle day).
  • Phase 4: Ischemia phase (from the 25th day of the cycle until the onset of menstruation). It is characterized by the decrease in progesterone, which leads to vasoconstriction of the blood vessels (vasoconstriction) of the endometrium (endometrium), resulting in the rejection of the mucosa.

Cycle monitoring

as part of cycle monitoring, a baseline determination is made to determine ovarian function at the beginning of the cycle (2nd – 5th day of the cycle). Typically, low estradiol and gonadotropin (FSH, LH) levels are found at this time. Note: If the FSH serum level is > 12 U/L at this time, an ovarian disorder is present, the cause of which must be clarified. If the LH peak, which precedes ovulation by one to two days, is to be detected, several LH measurements in the cycle are required. Usually, periovulatory (“around ovulation”) measurement of the follicle(s) is performed by ultrasound (folliculometry) including sonographic assessment of the endometrium. As part of the hormone analysis, estradiol and LH are measured in the middle of the cycle (once or several times). To clarify luteal function (corpus luteum phase), two to three progesterone determinations at intervals of two to three days in the second cycle phase (5-7 days after ovulation) are useful. In the early luteal phase, progesterone concentrations greater than 5 ng/ml are measured.