Steroids: Estrogens, Progestogens, and Androgens

Estradiol

What is the most potent estrogen produced by the body?

Both!

Is esterone a precursor or a metabolite of estradiol?

1/3rd

How many times is esterone less potent than estradiol?

In adipose tissue, from DHEA

Where is Esterone mainly produced?

Esterone

What estrogen primarily circulates the body after menopause?

Estriol; a metabolite of estradiol and significantly weaker

What estrogen is produced by the placenta during pregnancy?

They undergo less first pass metabolism than natural hormones, and so are effective at orally low doses. Fat soluble, adipose storage, and slow release mean they have prolonged action and higher potency.

What’s the benefit of synthetic estrogens?

Selective Estrogen Receptor Modulators; compounds that bind to estrogen receptors and exert effects, but are NOT steroidal.

What are SERMs?

Cholesterol

What is the main precursor of most sex hormones?

They diffuse across cell membranes and bind to specific nuclear complexes, initiating hormone specific RNA synthesis. This creates specific proteins that mediate a lot of functions. These are tissue specific.

How do steroids work? (simplified)

Menopausal therapy, contraception, hormonal deficiencies, hypogonadism, and gender transitions.

What is estrogen typically used for?

Vasomotor symptoms (hot flashes, cold sweats)

What is the indication for estrogen therapy in menopausal women?

Estradiol has low oral bioavailability, and is subject to extensive first pass effect.

Why is the administration of Estradiol usually nonoral?

Estrogens alone increases the risk of endometrial carcinoma (uterine cancer).

Why is estrogen often used in combination with a progestogen?

Nausea, breast tenderness. Less often, thromboembolic events, MI’s, and cancer.

What are the adverse effects of Estrogens?

It ends with “phene,” “fen,” or “fene".”

How can you tell a drug is a SERM?

Tamoxifen and Raloxifene

Which SERM’s are estrogen antagonists in breast tissue?

Raloxifine

Which SERM is an agonist in bone tissues?

Bazedoxifene

Which SERM antagonizes estrogen in the uterus, reducing the risk of cancer there?

Clomiphene

Which SERM stimulates ovulation (and can be used in infertility)?

Tamoxifen

Which SERM is used to treat/therapy for breast cancer?

Ospemifene

Which drug treats painful intercourse post-menopause?

Menopausal symptoms, many drug interactions, QT prolongation

What kind of adverse symptoms can Tamoxifen create?

Leg cramps and hot flashes; risk of embolisms

Raloxifene adverse effects?

Menopausal symptoms

Estrogens generally have what adverse effects?

Promotes accommodation of a new embryo and inhibits further ovulation.

What does progesterone primarily do?

Contraception, but can also control heavy menstrual bleeding, manage fertility and endometriosis, and treat dysmenorrhea

What are progestogens primarily used for?

Once daily

What is the most you would dose synthetic progestogens?

Headaches, depression, weight gain, libido changes, and acne.

Progestogen adverse effect profile?

Mifepristone

What is our one progesterone antagonist?

To terminate pregnancy

What is mifepristone used for?

Hormonal or non-hormonal

Contraceptives are either—

Contraceptives containing estrogen AND progestin

What are combination oral contraceptives?

A constant dose of both estrogen and progestin

What defines a monophasic COC?

They mimic the natural female cycle and contain a constant dose of estrogen with increasing doses of progestin

What defines a triphasic COC?

They’re a patch weekly for 3 weeks; ineffective for women weighing more than 90kg

How do transdermal contraceptive patches work?

A ring is inserted intravaginally once every 3 weeks, diffusing hormones into the vagina.

How do vaginal rings work?

Administered daily to deliver a low, continuous dosage. Less effective than most oral contraceptives, but more useful for breastfeeding patients

How do progestin only (mini) pills work?

One injection every 3 months, may delay fertility several months after discontinuation. May cause weight gain, should not be used longer than 2 years.

How does injectable progestin work?

Implant in the upper arm offers contraception for up to 3 years. Reliable and reversible; may cause bleeding and headaches.

How do progestin implants work?

Hormone loaded and Copper based

What are the two kinds of IUDs?

3 to 7 years; the copper version for up to 10

How long do IUDs prevent pregnancy?

72 hours

What is the window of time of most emergency contraception options?

Cerebrovascular and thromboembolic disease, liver disease, pregnancy, and estrogen-dependent

What are contraceptives contraindicated with?

Promote maturation in males, sperm production, increase hemoglobin and muscle proteins, decrease bone resorption

What do natural androgens do?

Hypogonadism, gender therapy and treat chronic wasting in HIV or cancer

What are androgens therapeutically used for?

Weight gain, acne, decrease breast size, deepening voice, and increased libido/hair growth. Increased LDL levels, increased risk of MI’s and stroke, and possible hepatic impairment

What is the androgen adverse profile?

Treat endometriosis and fibrocystic breast disease with its antiestrogenic properties

What is the androgen danazol used for?

No, typically. Testosterone undecanoate and related esters can.

Can testosterone be taken orally?

Methyltestosterone (causes hepatic dysfunction) and Oxandrolone

Which testosterone derivatives are active orally?

Androgen responsive cancers

What are antiandrogens typically used for?

Androgen antagonists and synthesis blockers

What are the two kinds of antiandrogens?

Finasteride and Dutasteride

Which antiandrogens prevent synthesis of androgens?