Estrogen


The two primary female sex hormones are estrogen and progesterone and you've seen in the last blog how they change across the menstrual cycle.

The follicular phase is fairly simple in that progesterone is very low and has very little effect overall with estrogen being the primary determinant of what is occurring physiologically. The surge of estrogen in the late follicular phase has a number of effects but the overall picture there is fairly simple. Things become more difficult in the luteal phase where estrogen first drops (this drop causing one set of effects) before both estrogen and progesterone increase and then fall again, causing different effects still. While I will discuss each hormone individually below, the simplest way of looking at this issue is that estrogen and progesterone have effectively opposite effects on a woman's physiology. Importantly, when progesterone is high during the luteal phase, its effects dominate as it blocks/opposes estrogen's effects.

Even here there is a further complication as estrogen sensitizes the progesterone receptor so that progesterone will have a larger impact during the luteal phase. In that sense, at least some of progesterone's overall effects are can be indirectly attributed to estrogen. Regardless, once I've looked at the effects of both estrogen and progesterone and consider the interactions (along with the spike of estrogen before ovulation), the overall structure of the menstrual cycle should make some logical sense in how it is trying to prepare a woman's body for the potentiality and eventuality of pregnancy.




Let's Look At Estrogen First


Estrogen is produced primarily by a woman's ovaries although it can be produced elsewhere, generally by the conversion of other hormones such as testosterone via aromatase.


Estrogen has its own specific receptor and there are two subtypes called estrogen receptor alpha and estrogen receptor beta. These are found in varying levels in different tissues in the body which not only explains how estrogen can have differential effects in different places but also why certain drugs that target specific receptors can be used to treat such diseases as breast cancer. In this case, it is estrogen receptor alpha that is primarily at play and drugs that specifically block that receptor allow estrogen to work in other tissues that express estrogen receptor beta while still treating the disease itself.


In the same way that testosterone is responsible for the development of male secondary sexual characteristics, estrogen has a primary effect on the development of female secondary sex characteristics. Estrogen is critically involved in the deposition of breast fat and contributes both to women's increased overall body fat levels and her lower body fat patterning. In men estrogen can have the same effect, for example and some males develop gynecomastia, the development breast tissue, under some conditions such as puberty or testosterone abuse.

High levels of estrogen can also cause water retention. Estrogen causes the growth plates of bones to close and this is part of why women are typically shorter than men; at puberty their bones fuse and stop lengthening. Critically, estrogen is a major player in increasing bone density although it is not the only factor here. Estrogen also plays a role in cognition and

mental function.

Estrogen dominates during the follicular phase (first half of the cycle), starting at a low level and gradually increasing to a surge prior to ovulation. It then drops before rising gradually during the luteal phase, reaching a level about half of that of the peak during the follicular phase.

Since estrogen has typically been blamed for a woman's issues with body fat, let me start with its effects in this regard. It turns out that estrogen has both positive and negative impact on fat metabolism, fat cells and fat loss although, in the aggregate most of its effects are positive. I should mention that one very confusing issue regarding the role of estrogen and body fat in women is that it has different effects in different parts of the body.

This is a large contributor to the typical fat patterns in women. Estrogen can impact negatively on thyroid levels which can have an indirect effect on body fat by lowering metabolic rate; estrogen also has a number of other potential negative effects on body fat. I haven't talked about how fat stores or mobilizes fat yet but estrogen does increase the levels of a specific receptor in fat cells (the alpha-2 receptor) that inhibits the release of fat from fat cells by decreasing the fat mobilizing effect of hormones released during exercise. These receptors are found to a greater degree in women's lower body and this is one way that estrogen may at least indirectly impact on body fat levels in the lower body. In contrast, estrogen does not impact on the levels of the alpha-2 receptor in the upper body and increases the fat cell's sensitivity to fat mobilizing hormones.


Estrogen thickens the connective tissue in the skin and fat matrix in the lower body and this is the primary cause of cellulite. What is happening is that excess body fat pushes through the connective tissue and you can think of it as a holiday ham pushing through the mesh it comes wrapped in. Cellulite is not a different type of fat and it doesn't respond to nearly any of the supposed treatments for it short of some invasive almost surgical treatments (fat loss generally improves its appearance).

The presence or absence of cellulite seems to be partially genetic (perhaps due to elevated estrogen levels, beyond that, most of estrogen's other effects are relatively positive in terms of body weight and body fat levels. First, there is an enzyme in fat cells called lipoprotein lipase (LPL) which breaks fatty acids off of what are called chylomicrons (produced after fat is eaten) for storage. Unless levels are very low, estrogen inhibit the activity of LPL in lower body fat cells inhibiting fat storage in that area.


Estrogen also inhibits the storage of visceral fat which is at least part of why it is protective against heart disease.

While LPL was long-considered the singularly important enzyme for fat storage, there is a second, far more important enzyme responsible for fat storage in fat cells called acylation stimulating protein (ASP) that plays a far larger role. While progesterone (discussed next) affects ASP, estrogen does not. Estrogen also increases LPL activity in muscle cells which causes fat to be stored there as Intramuscular Triglyceride (IMTG). These provide a quick source of energy during certain types of exercise and women's higher levels of estrogen cause them to store more IMTG than men. Estrogen also increases the level of fat- burning enzymes in skeletal muscle along with activating a compound (called AMPk) which enhances the use of fat for fuel.