Leptin and Reproductive Health

For some time now leptin has been accepted as a hormone that plays a role in the bodies maintenance of hypothalamic equilibrium in the body. Leptin is a long term regulatory factor that plays a role in energy and weight by managing the retention of adipose fatty tissues. For years after its discovery leptin was praised as a miracle weight loss hormone, because of its ability to control food intake drives in the body. However due to the intricacies of the metabolic processes associated with leptin there is still much up for debate about the the mechanisms behind leptin’s role in the body. Specifically, the relationship that female reproduction and metabolism have with leptin in the endocrine system remains an unsolved puzzle. Don’t worry, I will do my best to put the pieces together!

Leptin has far reaching roles in energy output and storage, the mechanisms and effects of this are something still being explored!

Over the lifetime of a female person, her leptin level will fluctuate in some important ways! Leptin in men also varies with age and works a little differently. In general leptin increases in women with age age while it decreases in men with age, but for the sake of simplicity we will focus on only the changes in women. Puberty is when leptin first becomes interesting.

The second stage of puberty brings about early breast development, pubic hairs, and changes in body fat storage. Behind this is flush of increased hormones, including…you guessed it leptin! Some of the mystery comes from a chicken or the egg type scenario. Since fatty adipose tissue secretes leptin, and fat storage increases in women with puberty. It makes sense that leptin secretion would increase as fat stores increase. Thus it is unclear if the increase in fat is due to leptin, or if leptin is a result of these changes. The rise of leptin levels more or less persists well past puberty and into adulthood, until menopause where leptin level decrease.

Puberty has many metabolic and physiological factors, leptin is associated with many of these.

Leptin has a 24hr daily cycle that is assumed to be related to the rise and fall of insulin due to food intake. In women, there is also a monthly cycle. Women with a healthy ovulation cycle will have a mid-secretory phase that increases progesterone secretion at the same time as leptin peaks. Studies have shown that fasting (semi-starvation) decreases leptin levels, while binging will increase hormone levels in the short term.

In the long term women with anorexia will be associated with characteristically low levels of leptin due to acute anorexia. As a result of this disease anorexic women will stop their menstruation cycle and become amenorrheic. This cessation of menstruation is due to the dangerously low levels of energy storage in the body. Which as a result sends signals that prevent the body from being able to become pregnant because it would not have the energy supply necessary to support a pregnancy. Some recent studies have shown promising results when such amenorrheic women are treated with leptin. This form of treatment has shown the potential to restore menstruation, ovulation, and even the ability to become pregnant in some women. However, it also is shown to cause weight loss which would cause complications in anorexic women who are already dangerously below weight. Still this treatment does reveal a connection between leptin levels and pregnancy.

In pregnancy leptin levels again increase with the progression of gestation, which is attributed to adipose stores and may also be due to the placental secretion of leptin. In later stages of pregnancy leptin resistance occurs to allow more nutrient fetal transmission. This process is essential to the growth and development of a healthy fetus. While BMI decreases the ability to ovulate, obesity brings its own complications to pregnancy. The excess fat storage in obese women alters the regulation of hormone via adipokine leptin secreting tissues, which is important for maternal metabolic homeostasis. As a result there is a variety of in utero energy transmission issues that arise from the hormonal irregularities in leptin secretion due to excess adipose tissue storage.

Overall, leptin is a pleiotropic neuropeptide hormone. The food intake habits indicative a specific leptin levels regulates energy storage in the body, which means that body weight is a downstream effect of the behavioral consequences of this hormone. As a result of these BMI fluctuations the ability to ovulate and carry out a pregnancy to term can either be supported or diminished. Since leptin levels are also associated with fetal nutrition this suggests that leptin may also play a role in the developmental health of the fetus. Meaning that extreme leptin levels (whether too high or too low) could be associated with developmental diseases.

An abstract representation of how adipocyte secretion of leptin regulates homeostasis.

In general, leptin levels regulate the production of adipose fatty tissues, which in turn secrete leptin. This is accomplished by sending signals to the brain that indicate the current state of fuel storage in the body. The brain interprets these signals like a gas gauge in a car, and then adjusting its energy spending habits accordingly. The brain tells the metabolism to increase when there is plenty of energy, but when the brain signals scarcity of energy then the metabolism rate plummets and then the weight packs on. Therefore the many effects that leptin levels are associated with in relation to metabolic homeostasis clearly has a role in the reproductive health of women. This relationship is complex and deeply connected in many metabolic processes.