# Obstetrics and Gynecology/Female Reproductive Physiology in the Non-Pregnant State
## Hormones and The Hypothalamo-Pituitary-Ovarian Axis

The basic architecture of the hypothalamo-pituitary-ovarian axis (HPO) is relatively simple, however the feedback mechanisms and changes create a layer of complexity. At a basic level,
* The hypothalamus secretes gonadotropin releasing hormone (GnRH), which acts on the
* Anterior pituitary gland to produce leutenizing hormone (LH) and follicle stimulating hormone(FSH)
* In turn, LH and FSH act at the ovary to induce production of progesterone, estrogen, and other steroid hormones such as androgens.
The more specific relationships will be elucidated further in the coming sections.

### Steroid Biosynthesis

Simply put, human steroidogenesis begins with the 27 carbon cholesterol molecule which is subsequently cleaved by specific enzymes into 21, 19, and 18 carbon structures presented in Table 1.
| Table 1: Products of Cholesterol Lysis |
| Enzyme | End product (Carbon Content) |
| C 20-22 lyase | Progesterone, glucocorticoids, mineralocorticoids (C-21) |
| 17-Hydroxylase/C 17-20 lyase | Androgens (C-19) |
| Aromatase | Estrogen (C-18) |

### The Menstrual Cycle

The menstrual cycle is a series of events in the female hormonal/structural reproductive system which result in ovum development, ovulation, and menstruation. It is divided into the follicular-proliferative and luteal-secretory phases. The menstrual cycle generally lasts 28 days. A general outline is provided in the figure below.
When studying the menstrual cycle, it is helpful to divide each phase into early, middle, and late stages. Under each category, one should be able to describe the initiating event of each stage, hormonal changes along the entire HPO axis, the feedback mechanisms in play (these change, and are critical to understand), the ovarian changes, and physical changes in the female reproductive tract.

#### The Follicular-Proliferative Phase
##### The Early Stage

The early stage of the follicular-proliferative phase begins with the low estrogen and progesterone concentrations remaining from the previous cycle. Menses ensues from low progesterone concentrations. These low concentrations also result in steadily increasing pulse frequency from the hypothalamus (GnRH release), which acts at the anterior pituitary to increase the concentrations of LH and FSH.
At this time, LH acts at the thecal cells to increase production of estrogen precursors--notably androstenedione, which moves to the follicular cells. Under the stimulation of FSH, granulosa cells house the transformation of androstenedione to estrogen. At the same time, 5-30 follicles will begin to mature under the stimulation of FSH.

##### The Middle Stage

Estrogen, produced from the granulosa cells at lower concentrations (at this point), inhibits LH and FSH production by the anterior pituitary, but stimulates further estrogen production through protecting growing follicles from atresia.
In contrast to the early stage of the follicular-proliferative phase, when menses occurs, the endometrium is now proliferating under the stimulation of estrogen.

##### The Late Stage

The key event of the late stage of the follicular-proliferative phase is the selection of a dominant follicle.