The main pathophysiology used to determine PCOS is the androgen excess when in turn manifest hirsutism (excess body hair) and hyperandrogenism. Androgen is in relation to free unbound testosterone in the body. High levels of androgen are produced by the ovaries and in turn subdue the amount of sex hormone-binding globulin which is why there is a higher amount of free testosterone. There are a network of factors that are altered in the body that are present during PCOS. The factors that are altered vary depending on the individual and is one of the reasons why it’s difficult to have one method to attempt to cure PCOS.
A couple of these alterations include steroidogenesis( responsible for biosynthesis steroid), ovarian folliculogenesis (maturation of ovarian follicles), insulin secretion/sensitivity, and adipose cell function (the storage of energy in at cells). Other factors are sympathetic (fight or flight) nerve function and inflammatory factors. The reason why these factors are varied based on the person is most likely due to environmental factors and day to day activities such as, food intake, and endocrine disruptors (things like pesticide, inhalants, toxins, ie. anything taken from the external environment into the body). Studies usually focus on the genes regulate or have to do with gonadotropic (released by anterior pituitary gland and increases sex hormone production) and insulin activity.
Ovum: unfertilized egg, also known as an oocyte
Estradiol: a form of estrogen
Androstenediones: a form of androgens
The ovarian cycle refers to follicle development and the release of hormones and ovum
The menstrual cycle refers to the growth and shedding of endometrial tissue. There are three phases: menstruation and the proliferative phase occur during the follicular phase of the ovarian cycle, and the secretory phase occurs during the luteal phase of the ovarian cycle.
The ovarian and menstrual cycles both occur in females for fertilization. The duration of both cycles is approximately 28 days and they occur simultaneously.
PCOS directly affects the ovarian cycle due to increased androgen production, which leads to high estrogen levels in the follicular phase. This prevents release of the ovum, which in turn affects the menstrual cycle.
The Follicular Phase starts at day one of the menstrual cycle. Follicle stimulating hormone (FSH) is secreted by the anterior pituitary gland. As the end of the menstrual cycle nears, estradiol and progesterone levels decrease, causing an increase in gonadotropin hormone-releasing hormone (GnRH) secreted from the anterior pituitary. The pulsatile secretion of GnRH leads to an increase in FSH levels. The increased FSH levels causes a few ovarian follicles to be recruited to mature. As the follicles grow, the number of granulosa cells increases, in turn increasing the number of FSH receptors that are only found on granulosa cell membranes. Theca cells in the follicle have LH receptors throughout the ovarian cycle. LH in the theca cells stimulates androstenedione production. Androstenedione is transported to granulosa cells, which convert it to estradiol. With estradiol present, FSH can stimulate formation of LH receptors on the granulosa cells. LH receptors on granulosa cells are different from those on theca cells because they can only be formed through FSH and estradiol stimulation. The formation of LH receptors on granulosa cells produces more estradiol, causing a positive feedback loop. As LH levels increase, FSH levels decreases. One dominant follicle is chosen to ovulate, the follicle secreting the highest amount of AMH, while the others degenerate (atresia). In the dominant follicle, the remaining FSH activates the aromatase enzyme, which converts androgens to estrogen. The increased estrogen levels stimulate formation of a new layer of endometrium and also stimulate areas in the cervix to produce cervical mucus to reduce vaginal acidity.
About 24 hours after the beginning of the LH surge, estradiol levels fall due to direct inhibition by progesterone. The loss of positive feedback by estradiol causes LH levels to decline. Progesterone also causes an increase in FSH levels. Ovulation occurs 10 – 12 hours after LH levels peak. The increased LH levels causes an increase in prostaglandins, which are activated in the wall of the now mature dominant ovarian follicle. Prostaglandins digest collagen in the follicular wall and rupture the follicle. They also stimulate ovarian smooth muscle to encourage release of the ovum (egg). The elevated levels of FSH help remove follicular attachments from the now free ovum.
The luteal phase comes after ovulation and lasts approximately 14 days. Granulosa and theca cells not released with the ovum continue to grow and develop a yellow color due to the pigment lutein. The luteinized cells attach to the ovary and become the corpus luteum, an endocrine organ that produces progesterone and estrogen. Progesterone causes the endometrium to prepare for pregnancy – blood vessels grow, glands begin to coil, and the cervical mucus thickens. Progesterone also inhibits FSH and LH release, which ensures that no other ovum or follicles develop. If no fertilization of the ovum occurs, the lack of LH in the ovary causes corpus luteum atrophy, The degeneration of the corpus luteum causes a decrease in progesterone and estrogen levels, which leads to an increase in FSH levels. The endometrium also degenerates, starting the next menstrual cycle. However, If fertilization of the ovum occurs, human chorionic gonadotropin (hCG) is released. hCG has a similar structure to LH and therefore keeps the corpus luteum intact to produce progesterone until the placenta is formed.
PCOS at the Cellular Level
PCOS can be characterized by a display of impaired insulin sensitivity but normal responsiveness in isolated adipocytes and impaired insulin responsiveness in skeletal muscle and myotubes. Individuals with PCOS show an excessive ovarian and/or adrenal androgen secretion. Intrinsic ovarian factors such as altered steroidogenesis and factors external to the ovary such as hyperinsulinemia contribute to the excessive ovarian androgen production.
The lunar and follicular phase don't peak in PCOS