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Progesterone: What do we know

Oestrogen is the first hormone that comes to mind when talking about menopause. There are other important hormones however such as progesterone. This, together with oestrogen and testosterone maintain the balance of women’s delicate hormonal system.

What is it exactly?

Progesterone (P4) is defined as an endogenous steroid. This and the progestogen sex hormone are involved in the menstrual cycle, pregnancy, and embryogenesis of people. It belongs to a group of steroid hormones called the progestogens (hence the name!).

P4 is released by the ovaries. Similar to oestrogen, P4 levels can change, and this can contribute to irregular menstrual periods and menopausal symptoms. Progesterone is also essential for implantation of the fertilized egg in the uterus.

How is synthetic progesterone made?

Synthetic progesterone is usually lab-made. It is used to imitate the progesterone released by the ovaries. Cosmetic progesterone products (can be applied to the skin) do not require a doctor’s approval before marketing, so it is important to be careful with these products. There is currently no limit on the amount of p4 allowed in cosmetic products. In 1993 the FDA in the USA proposed a rule to limit the amount of progesterone in cosmetics products, but this rule was never finalized. So make sure you know what is going on your skin.

What is it used for?

Taking synthetic progesterone by mouth and applying progesterone gel into the vagina can help premenopausal women who are not getting their periods. Micronized p4 is approved and safe for this use, as is intravaginal progesterone gel (Crinone 4%).

Why do women take progesterone?

Menstrual cycle

It is common to take progesterone when a woman’s period unexpectedly stops. This helps the menstrual cycle to start again. It can also be used to treat uterine bleeding caused by hormonal imbalance, and treat severe symptoms of premenstrual syndrome (PMS).

HRT

Progesterone is also used combined with oestrogen as part of Hormone Replacement Therapy (HRT) for menopausal women. This is known as combined HRT. If oestrogen is given without progesterone, it makes the risk of uterine cancer higher. Because of this, oestrogen-only HRT is usually only given to women that have had their uterus removed.
Progesterone is also used for other conditions, but there is a lack of scientific evidence to support these uses.

What is progestin?

Progestin is the term used to refer to the progesterone made in the laboratory. This is found in oral contraceptives and it is also used for hormone replacement therapy. “Natural progesterone,” and some prescription products including Prometrium and Crinone, are made from a chemical called diosgenin which is made from yam or soy. In the laboratory, it is then turned into progesterone.

However, it is important to know that the human body is not able to make this conversion by itself. So, eating yam or soy will not boost your progesterone levels.

 

What is Progesterone used for?

Taking progesterone by mouth and applying progesterone gel into the vagina are used to help premenopausal women who do not get a period. Micronized progesterone is approved and safe for this use, as is intravaginal progesterone gel (Crinone 4%).

HRT

Micronized progesterone (Prometrium) is approved and safe for paired use with oestrogen as a component of HRT for menopausal women. Research shows that adding progesterone to HRT protects against the side effects of oestrogen.

 

Infertility

Intravaginal progesterone gel (Crinone 8%) is approved for use as a part of infertility treatment in women. 

Menopause symptoms 

There is increasing evidence that applying a specific progesterone cream (Progest) to the skin can be effective in reducing symptoms such as hot flushes in menopausal women.

Preterm birth 

Most research suggests that applying progesterone gel or inserts into the vagina, alone or along with therapy to delay labour, can reduce the risk of premature birth in some women which are at high risk of premature birth. However, other research suggests the opposite. More research is required.

Miscarriage

Most research shows that applying progesterone into the vagina does not reduce the risk of having a miscarriage in women who are bleeding during pregnancy or with a history of miscarriages in the past. However, some early research suggests that taking progesterone by mouth might reduce the risk of miscarriage in women who are bleeding during pregnancy. Even for this topic, more research is needed.

Premenstrual syndrome (PMS). 

Some clinical research suggests that applying progesterone into the vagina or the rectum before menstruation reduces symptoms of PMS, most of the recent evidence shows that giving progesterone by mouth or rectally does not reduce PMS symptoms.

Side effects

Does progesterone have some side effects? Yes. Progesterone can cause many side effects including stomach upset, changes in appetite, weight gain, fluid retention and swelling (oedema), fatigue, acne, drowsiness or insomnia. Skin rashes, hives, fever, headache, depression, breast discomfort or enlargement, and other minor side effects.

Progesterone and oestrogen are both hormones. They are often taken together, especially in menopausal symptoms treatment. Progesterone can decrease some of the side effects of oestrogen. But progesterone might also decrease the beneficial effects of oestrogen. Taking progesterone along with oestrogen might cause/increase breast tenderness. The choice of which treatment is best completely depends on the person’s medical history and personal choice. It is best to get recommended by a medical professional.

Which are the common doses?

Hormone Replacement Therapy (HRT): 200 mg micronized progesterone (Prometrium) per day, typically taken for 12 days of a 25-day cycle with 0.625 mg conjugated oestrogen.

For symptoms of menopause: 20 mg progesterone cream (equivalent to 1/4 teaspoon Progest cream), typically applied daily to rotating places on the body including upper arms, thighs, or breasts.

 

REFERENCES

  • J Clin Endocrinol Metab. 2020 May 1;105(5). pii: dgz262. doi: 10.1210/clinem/dgz262.
  • The Effect of Perimenopausal Transdermal Estradiol and Micronized Progesterone on Markers of Risk for Arterial Disease. Gordon JL, Rubinow DR, Watkins L, Hinderliter AL, Caughey MC, Girdler SS. Climacteric. 2019 Dec;22(6):535-537. doi: 10.1080/13697137.2019.1663625.
  • Will estradiol/progesterone capsules for oral use become the best choice for menopausal hormone therapy?  Mueck AO, Ruan X. Menopause. 2019 Nov;26(11):1318-1323. doi: 10.1097/GME.0000000000001398.
  • Effects of perimenopausal transdermal estradiol on self-reported sleep, independent of its effect on vasomotor symptom bother and depressive symptoms. Geiger PJ, Eisenlohr-Moul T, Gordon JL, Rubinow DR, Girdler SS. Menopause. 2019 Sep;26(9):966-971. doi: 10.1097/GME.0000000000001356.
  • Determination of estradiol and progesterone content in capsules and creams from compounding pharmacies. Stanczyk FZ, Niu C, Azen C, Mirkin S, Amadio JM. Expert Rev Clin Pharmacol. 2019 Aug;12(8):729-739. doi: 10.1080/17512433.2019.1637731. Epub 2019 Jul 22.
  • A combined, bioidentical, oral, 17?-estradiol and progesterone capsule for the treatment of moderate to severe vasomotor symptoms due to menopause. Archer DF, Bernick BA, Mirkin S. Hum Reprod Update. 2019 Mar 1;25(2):257-271. doi: 10.1093/humupd/dmy039.
  • The route of administration, timing, duration and dose of postmenopausal hormone therapy and cardiovascular outcomes in women: a systematic review. Oliver-Williams C, Glisic M, Shahzad S, Brown E, Pellegrino Baena C, Chadni M, Chowdhury R, Franco OH, Muka T.