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Estrogen and progesterone

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Estrogen and progesterone

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Estrogen and progesterone

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is a female hormone that has a mild thermogenic action, increasing basal body temperature during the luteal phase of the menstrual cycle. 

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A 20-year-old female presents to the clinic with the complaints of irregular menstrual bleeding and breast tenderness. History reveals two months ago she was placed on medroxyprogesterone acetate injections for contraception. A urine pregnancy test at that time was negative. She is sexually active with one partner and does not use condoms during intercourse. The patient's symptoms are most likely due to which of the following?

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Content Reviewers:

Rishi Desai, MD, MPH

Estrogen and progesterone are the female sex hormones, and they’re produced mainly by the ovaries - the female gonads.

The female body can synthesize 3 types of estrogens: estradiol, estrone and estriol.

Of the three, the ovaries synthesize estradiol, which is the most biologically active of them all, and accounts for the majority of sex-specific changes that begin in puberty - like monthly ovulation and menstruation as well as the development of the secondary sex characteristics.

Small amounts of estrogen are also produced by the adrenal cortex and fat cells in adipose tissue, and the placenta secretes these hormones during pregnancy, as well.

But during the reproductive period, it’s the ovaries that produce the majority of estrogen and progesterone in the female body.

Before puberty, the hypothalamus secretes small amounts of a hormone called gonadotropin-releasing hormone, or GnRH.

That GnRH travels to the nearby pituitary, which secretes two hormones of its own - follicle stimulating hormone, or FSH, and luteinizing hormone, or LH.

Once puberty hits, the hypothalamus starts to secrete GnRH in pulses, sometimes more and sometimes less, and FSH and LH make the ovarian follicles develop and secrete hormones.

The ovarian follicles are scattered throughout the ovaries, and each ovarian follicle is made up of a ring of follicular cells surrounding a primary oocyte at its core.

As the ovarian follicles develop, the follicular cells differentiate into theca cells and granulosa cells, which both play a role in the synthesis of progesterone and estrogen.

How much of these hormones is secreted is directly related to the phases of the female menstrual cycle.

The menstrual cycle lasts 28 days on average, and it’s centered around a surge of FSH and LH happening on day 14 - which makes ovulation possible.

The variations in FSH and LH levels result in fluctuating levels of estrogen and progesterone that vary according to the phases of the menstrual cycle - the two weeks before ovulation are called the follicular phase, during which mostly estrogen is produced.

The two weeks following ovulation are called the luteal phase, during which progesterone is the dominant hormone.

During the follicular phase of the menstrual cycle, estrogen makes the superficial layer of the uterus, the endometrium, thicken up and sprout progesterone receptors.

During the follicular phase, estrogen acts as a negative feedback signal, making the pituitary secrete less FSH as estrogen levels rise.

Right before ovulation, the really high estrogen levels make the pituitary much more sensitive to the actions of hypothalamic GnRH, and so, they turn into a positive feedback signal, leading to a massive surge of FSH and LH that leads to ovulation.

During the luteal phase, progesterone binds to receptors in the endometrium, and stimulates the endometrial glands to produce more secretions that prepare the uterus for a potential pregnancy.

Progesterone acts as a negative feedback signal during the luteal phase - making the pituitary secrete less LH.

In turn, the levels of progesterone decrease as well, and menstruation follows.

Both estrogen and progesterone are steroid hormones, so their production starts with cholesterol.

Cholesterol reaches the theca cells, and inside there’s an enzyme called cholesterol desmolase, which converts cholesterol to pregnenolone.

Another enzyme in theca cells called 3-beta-hydroxysteroid dehydrogenase converts some of the pregnenolone into progesterone.

However, most of the pregnenolone is converted to 17-hydroxypregnenolone, and then into dehydroepiandrosterone, or DHEA.

3-beta-hydroxysteroid dehydrogenase, is quite the over achieving enzyme because it also acts on DHEA and converts it into androstenedione - a testosterone precursor.

Sources
  1. "Medical Physiology" Elsevier (2016)
  2. "Physiology" Elsevier (2017)
  3. "Human Anatomy & Physiology" Pearson (2018)
  4. "Principles of Anatomy and Physiology" Wiley (2014)
  5. "Biochemistry of aromatase: significance to female reproductive physiology" Cancer Res (1982)
  6. "Androgen production in women" Fertil Steril (2002)
  7. "Progesterone and Testosterone Hydroxylation by Cytochromes P450 2C19, 2C9, and 3A4 in Human Liver Microsomes" Archives of Biochemistry and Biophysics (1997)