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Progesterone

Progesterone is produced in the corpus luteum. The corpus luteum is in the ovaries. It’s the remant of the follicle of where ovulation took place that month. So the ova comes from that follicle in the ovary and the remnant of that follicle becomes the corpus luteum and then it produces progesterone. So on day 14 is where we have this occur. On day 28 is also when the corpus luteum disappears and there won’t be anymore progesterone produced. In order for there to be a corpus luteum, ovulation must take place. If ovulation doesn’t take place on day 14, that means the uterus is totally under the control of estrogen and bleeding may take place mid-cycle because there’s nothing to counteract the estrogen.

Progesterone is regulated by luteinizing hormone. The corpus luteum regresses after 14 days if ovum is not fertilized. If the ovum is fertilized the corpus luteum does not regress and continues to make progesterone, therefore no bleeding at the end of the month. Progesterone prepares the endometrium for implantation. It also increases the basal body temperature by 1C.

All of this should just be a review of things you know already, if anything sounds unclear, review how the menstrual cycle works.

Therapeutic use of progesterone

Uterine Bleed due to ovulatory failure: If there’s no ovulation, the uterus is totally under the control of estrogen and bleeding happens mid-cycle. If this happens on a monthly basis, we must give progesterone mid cycle for 10 days to stop the bleeding from happening. This therapy will go on for several months hoping the ovulation will occur in the next cycle.

Dysmenorrhea: Painful periods are controlled by birth control pills which include both estrogen and progesterone.

Contraception: Progesterone could be used alone for contraception. When you give estrogen, you must give progesterone, but when you give progesterone alone, you don’t have to give an estrogen. When you typically deal with an estrogen/progesterone combination, you’re typically giving the medication for 21 days (21 active pills and 7 placebo pills). So it’s 21 days on and 7 days off.

When we deal with progesterone alone, they’re getting progesterone for 28 days. It could be in the form of pills or a long-acting injection. So the blood levels for progesterone are not dropping. As a result there is no true bleeding.

Endometrial cancer: Progesterone is a palliative treatment (not a cancer chemotherapy drug) that helps decrease progression of the disease.

Progesterone Agents

Megestrol (Megace) – p.o. – Used for endometrial cancer. There’s also a non-hormonal use for it, often in the elderly or cancer patients (non hormonal cancer) that is used to induce appetite.
Norethindrone (Norlutin) – p.o. – Used for ovulatory failure (in that mid-cycle over a 10 day course of medication). It’s also used as the progesterone component in many of the BC pills.
Medroxyprogesterone (Provera) – p.o., inj. – Used in menopausal individuals to protect the uterus from the estrogen they’re taking. There’s also a long-acting injection of it used as a BC that’s used once every 3 months.
Ethynodiol (Ovulen) and Norgestrol (Ovral): These are also commonly the progesterone components used with estrogen for birth control pills.

Oral & Patch Contraceptives

These are 99% effective because people are compliant with it. There is generally a caution for the first month and another form of contraceptive is encouraged in the mean time. There’s two ways progesterone works as a contraceptive:

Stop ovulation
Cervical gland produces mucous so that sperm can’t pass through

Progesterone could be administered alone daily
Progesterone with an estrogen is typically administered for 21 days (7 days off). The patch is 3 weeks on and the 4th week has no patch. There are a few drugs that differ from this.
If someone wants to get pregnant, it’s recommended they stop BC for 3 months because the BC has been purposely causing ovulatory failure.

Progesterone Side Effects

Nausea/vomiting
Headache
Weight gain

Most of these three side effects above tend to go away with time.

Acne: If acne occurs, they can try triphasic BC pills. Instead of 21 days of the same level of progesterone, it varies it to mimic the actual cycle. That means the early phase is low in progesterone. In the middle phase it peaks and in the third it drops again. The triphasic is 99% effective. There’s no advantage of efficacy with it. The only advantage is that there’s a lower incidence of acne.

Melasma: This is moreso of an adverse reaction (brown pigment spots on the face) which is unfortunately permanent.

Long Term Risks

Decreased fertility: The longer a person is on BC, the more difficult it may be for them to be

Thromboembolism: Increased risk of clotting, stroke, heart attack, especially in smokers and older people.

Cancer: There’s controversy about this but in terms of breast cancer, BC pills tend to show that it lowers the risk, although some studies show the opposite conclusion.