Progesterogens: Progesterone and Progestin unpacked

What are Progestogens

Progestogens is a collective term that encompasses natural progesterone, and a range of synthetic drugs termed progestins, manufactured to resemble progesterone and used in the oral contraceptive pill and combination HRT products.

Progesterone

Progesterone is made in high levels by the ovaries after ovulation in menstruating women and in low doses by the adrenal glands for women of all ages. Progesterone that is manufactured from a vegetable base( soya or yam) in a as a medicine is identical to the progesterone made by ovaries and adrenals , and therefore "bio & body-identical," possessing the same whole body actions as our a woman’s own hormone.

Progesterone receptors are found in the uterus, breast, ovary, brain, bone, musculoskeletal and immune systems as well as in all cells and tissues. As such, the endogenous ( the body producing itself) production of progesterone is an essential regulator of female reproductive function and plays an integral role in the normal physiology of the cardiovascular system,musculoskeletal, nervous and immune system.

In other words, progesterone is needed for body -wide health, not just reproduction

Actions of endogenously produced & bio-indentical progesterone:

• Anti oestrogenic (counter balances oestrogens proliferic action)

• Anti androgenic (prevents androgens like testosterone and dihydrotestosterone from mediating their biological effects in the body, which in women presents as acne, hair loss & hirsutism)

• Antimineralcorticoid (induce a transient reduction in (aldosterone-induced) water retention

• A neurosteroid; progesterone is metabolized (broken down) into allopregnanolone and pregnanolone, which potent activators of the GABAA receptor delivering anxiolytic (calm anxiety), anticonvulsant, sedative, hypnotic, euphoriant, and muscle relaxant properties.

Progestins

By comparison , progestins are chemicals used in both HRT and contraception, that can be termed so if they meet two criteria: 1) maintain a pregnancy by way of changing the uterine lining to allow implantation of a fertilized egg 2) prevents further ovulation during pregnancy. They also possess other actions, due to their affinity to bind to androgen, glucocorticoid, and mineralocorticoid receptors, as well as the progesterone receptor. Jerrilynn Prior, calls these progestins “synthetic knock-offs", I wish I’d come up with that phrase!

Let’s look at some examples; androgenic progestins can prevent oestrogen’s natural lowering effect of the hepatic synthesis of HDL (good) cholesterol, triglycerides, coagulation and fibrinolysis factors, angiotensinogen, and hormone-binding globulins. As such these androgenic progestins in many forms of HRT (and contraceptive pills ) can cause weight gain, acne, hirsuitism, female patten hairloss & fluid retention.

The two most notable androgenic progestins used in HRT products are levonorgestrel and norethindrone. - see brands and how delivered i.e tablet, IUD or patch below:

Progestin	Brands	Delivery
Levonorgestrel	Mirena  Combined patches FemSeven conti	IUD Patch
Norethisterone	Combined patches  Evorel conti & Sequi Combined tablets Kliovance Kliofem Novofem Trisequens Estelle Duet	Patch Tablets Tablets  Tablets Tablets

Progestins with glucocorticoid activity may increase the process by which a blood clot is formed in vessel walls. The most notable glucocorticoid progestin used in HRT is Medroxyprogesterone acetate. See brands and delivery below:

Progestin	Brands	Delivery
Medroxyprogesterone acetate	Combined tablets Indivina  Solo Provera	Tablets  Tablets

Classification of progestins

Progestin’s classification is based on it’s structural properties, of which there are 3 major groupings; pregnanes, estranes, and gonanes. Pregnanes are derived from progesterone, and the latter 2 are derived from testosterone. Estranes have more androgenic activity than gonanes. The testosterone derivatives are the majority of progestins used in contraceptives. Each of the progestin drugs is listed by their grouping:

• Pregnanes (Progesterone derivatives): medroxyprogesterone acetate, nomegestrol acetate

• Estranes (Testosterone derivatives) : Norethindrone, norethindrone acetate, ethynodiol diacetate, norethynodrel

• Gonanes (Testosterone derivatives): levonorgestrel, desogestrel, norgestimate, gestodene

Thirdy, considered a retroprogestrone, Dydrogesterone is structurally and pharmacologically similar to natural progesterone,has good oral bioavailability and few side effects. Dydrogesterone has no androgenic effects. See brands and delivery below;

Progestin	Brands	Delivery
Dydrogesterone	Femeston range  Duphaston	Tablets Tablets

Finally, as a spiralocatone dereivative, Drospirenone,  a novel progestin with antimineralocorticoid and antiandrogenic activity. See brands and delivery below;

Progestin	Brands	Delivery
Drospirenone	Combined tablets Angeliq

Progestins By Generation

Progestins are also classified by generation, based upon when the group of progestins was introduced into the market, regardless of structure derivation, and consists of the first, second, third, and fourth-generation agents. The majority of progestins in all three generations are derived from testosterone and therefore exhibit undesirable androgenic effects because, despite modifications, they still bind to the androgen receptor, which as explained previously will often in women result in weight gain , acne, hirsuitism, female patten hairloss & fluid retention.

The newer, fourth-generation progestins have been developed to be closer in activity to progesterone to avoid these adverse effects. and have some antiandrogenic properties.

Selecting a progestogen

As tolerability to progestogens varies considerably among women, treatment must be individualized. Treatment should begin with a progestogen that has the lowest risk profile regarding breast cancer and cardiovascular effects, while addressing her specific needs and risk factors. Numerous opinion leaders such as Dr. Jerilynn C. Prior, guideline groups, and menopause societies recommend as the gold standard choice micronized progesterone or secondly dydrogesterone to estrogen therapy as the associated cardiovascular, thromboembolic, and breast cancer risks are lower with these molecules compared with other progestogens. When we appreciate the multiple actions of progesterone, and which receptors these progestins effect- androgen, glucocorticoid, and mineralocorticoid ( see chart below) we can see why this is the preferential choice, and how we can better select a progestogen that suits the clients case and background.

Progestagens as either Progesterone  Progestin	Brands	Delivery	Hormonal Activity  AE- antioestrogenic AND- androgenic AA-antiandrogenic AM-antimineralcorticoid GLU=glucocorticoid EST- oestrogenic
Progesterone	Utrogestan	Capsules	AE|AA|AM
Progesterone +  estradiol hemihydrate	Bijuve	Capsules	AE|AA|AM
Levonorgestrel	Mirena  Combined patches FemSeven conti	IUD Patch	AE|AND|
Norethisterone	Combined patches  Evorel conti & Sequi Combined tablets Kliovance Kliofem Novofem Trisequens Estelle Duet	Patch Tablets Tablets  Tablets Tablets	AE|EST|EST|
Dydrogesterone	Femeston range  Duphaston	Tablets Tablets	AE| weak AM
Medroxyprogesterone acetate	Combined tablets Indivina  Solo Provera	Tablets Tablets	AE| weak AND|GLU
Drospirenone	Combined tablets Angeliq		AE|AA