[1] Other side effects of estrogens include an increased risk of blood clots, cardiovascular disease, and, when combined with most progestogens, breast cancer.

They have important effects in many tissues in the body, including in the female reproductive system (uterus, vagina, and ovaries), the breasts, bone, fat, the liver, and the brain among others.

[3][4][6][5][1] Estrogens have contraceptive effects and are used in combination with progestins (synthetic progestogens) in birth control to prevent pregnancy in women.

Estrogen and other hormones are given to postmenopausal women in order to prevent osteoporosis as well as treat the symptoms of menopause such as hot flashes, vaginal dryness, urinary stress incontinence, chilly sensations, dizziness, fatigue, irritability, and sweating.

Estrogen appears to have a protector effect on atherosclerosis: it lowers LDL and triglycerides, it raises HDL levels and has endothelial vasodilatation properties plus an anti-inflammatory component.

Estrogen is also used in the therapy of vaginal atrophy, hypoestrogenism (as a result of hypogonadism, oophorectomy, or primary ovarian failure), amenorrhea, dysmenorrhea, and oligomenorrhea.

[17] Its effectiveness is approximately equivalent to that of antiestrogen therapy with selective estrogen receptor modulators (SERMs) like tamoxifen and aromatase inhibitors like anastrozole.

[40] Estrogen-induced growth attenuation was used as part of the controversial Ashley Treatment to keep a developmentally disabled girl from growing to adult size.

[45][46] However, it has been found to produce many side effects (e.g., gynecomastia, feminization, cardiovascular disease, blood clots), and so is no longer recommended for such purposes.

[45] High incidence of sexual dysfunction has similarly been associated with high-dose estrogen therapy in men treated with it for prostate cancer.

[1] Testosterone, prasterone (dehydroepiandrosterone; DHEA), boldenone (δ1-testosterone), and nandrolone (19-nortestosterone) are naturally occurring androgens/anabolic steroids (AAS) which form estradiol as an active metabolite in small amounts and can produce estrogenic effects, most notably gynecomastia in men at sufficiently high dosages.

High doses of synthetic estrogens like ethinylestradiol and diethylstilbestrol can produce prominent untoward side effects like nausea, vomiting, headache, malaise, and dizziness, among others.

[1] Due to its effects on liver protein synthesis, oral estrogen is procoagulant, and has been found to increase the risk of venous thromboembolism (VTE), including of both deep vein thrombosis (DVT) and pulmonary embolism (PE).

[1] Conversely, modern oral contraceptives are not associated with an increase in the risk of stroke and myocardial infarction (heart attack) in healthy, non-smoking premenopausal women of any age, except in those with hypertension (high blood pressure).

[92][93] However, a small but significant increase in the risk of stroke, though not of myocardial infarction, has been found in menopausal women taking hormone replacement therapy.

[95] Menopausal hormone therapy with replacement dosages of estrogens and progestogens has been associated with a significantly increased risk of cardiovascular events such as VTE.

[97] This is of importance because conjugated estrogens have been found to be more resistant to hepatic metabolism than estradiol and to increase clotting factors to a greater extent.

[97][96] In contrast to oral estrogens as a group, transdermal estradiol at typical menopausal replacement dosages has not been found to increase the risk of VTE or other cardiovascular events.

[111][112] In addition, smoking has been found to exponentially increase cardiovascular mortality in conjunction with combined oral contraceptive use and older age.

[1] Through these effects, both oral and transdermal estrogens can protect against atherosclerosis and coronary heart disease in menopausal women with intact arterial endothelium that is without severe lesions.

[120][121][122] SHBG levels with birth control pills containing different progestins are increased by 1.5 to 2-fold with levonorgestrel, 2.5- to 4-fold with desogestrel and gestodene, 3.5- to 4-fold with drospirenone and dienogest, and 4- to 5-fold with cyproterone acetate.

[132][133] In accordance, antiestrogens like the selective estrogen receptor modulator (SERM) tamoxifen, the ER antagonist fulvestrant, and the aromatase inhibitors (AIs) anastrozole and exemestane are all effective in the treatment of ER-positive breast cancer.

[140][141] A 2017 systematic review and meta-analysis of 14 studies assessed the risk of breast cancer in perimenopausal and postmenopausal women treated with estrogens for menopausal symptoms.

[142] They found that treatment with estradiol only is not associated with an increased risk of breast cancer (ORTooltip odds ratio = 0.90 in RCTsTooltip randomized controlled trials and OR = 1.11 in observational studies).

[137][138][139] However, there are indications that there may be a ceiling effect such that past a certain low concentration threshold (e.g., approximately 10.2 pg/mL for estradiol), additional estrogens alone may not further increase the risk of breast cancer in postmenopausal women.

[143] There are also indications that the fluctuations in estrogen levels across the normal menstrual cycle in premenopausal women may be important for breast cancer risk.

However, the dramatically increased risk of breast cancer (20- to 58-fold) in men with Klinefelter's syndrome, who have somewhat of a hybrid of a male and a female genotype (47,XXY), suggests that it may have to do with the sex chromosomes.

[217] Conjugated estrogens (brand name Premarin) was introduced in 1941 and succeeded Emmenin, the sales of which had begun to drop after 1940 due to competition from DES.

[229][230] After a sufficient course of therapy, only Sertoli cells and spermatogonia remain in the seminiferous tubules of the testes, with a variety of other testicular abnormalities observable.

[228][229] The use of estrogens for contraception in men is precluded by major side effects such as sexual dysfunction, feminization, gynecomastia, and metabolic changes.