# Estropipate

Estropipate, also known as piperazine estrone sulfate and sold under the brand names Harmogen, Improvera, Ogen, Ortho-Est, and Sulestrex among others, is an estrogen medication which is used mainly in menopausal hormone therapy in the treatment of menopausal symptoms. It is a salt of estrone sulfate and piperazine, and is transformed into estrone and estradiol in the body. It is taken by mouth.

## Medical uses

Estropipate is used to:
* Alleviate symptoms of menopause as menopausal hormone therapy
* Treat some types of infertility
* Treat some conditions leading to underdevelopment of female sexual characteristics
* Treat vaginal atrophy
* Treat some types of breast cancer (particularly in men and postmenopausal women)
* Treat prostate cancer
* Prevent osteoporosis
vte Estrogen dosages for menopausal hormone therapy :
| Route/form | Estrogen | Low | Standard | High |
| Oral | Estradiol | 0.5–1 mg/day | 1–2 mg/day | 2–4 mg/day |
| Oral | Estradiol valerate | 0.5–1 mg/day | 1–2 mg/day | 2–4 mg/day |
| Oral | Estradiol acetate | 0.45–0.9 mg/day | 0.9–1.8 mg/day | 1.8–3.6 mg/day |
| Oral | Conjugated estrogens | 0.3–0.45 mg/day | 0.625 mg/day | 0.9–1.25 mg/day |
| Oral | Esterified estrogens | 0.3–0.45 mg/day | 0.625 mg/day | 0.9–1.25 mg/day |
| Oral | Estropipate | 0.75 mg/day | 1.5 mg/day | 3 mg/day |
| Oral | Estriol | 1–2 mg/day | 2–4 mg/day | 4–8 mg/day |
| Oral | Ethinylestradiol$^a$ | 2.5–10 μg/day | 5–20 μg/day | – |
| Nasal spray | Estradiol | 150 μg/day | 300 μg/day | 600 μg/day |
| Transdermal patch | Estradiol | 25 μg/day$^b$ | 50 μg/day$^b$ | 100 μg/day$^b$ |
| Transdermal gel | Estradiol | 0.5 mg/day | 1–1.5 mg/day | 2–3 mg/day |
| Vaginal | Estradiol | 25 μg/day | – | – |
| Vaginal | Estriol | 30 μg/day | 0.5 mg 2x/week | 0.5 mg/day |
| IMTooltip Intramuscular or SC injection | Estradiol valerate | – | – | 4 mg 1x/4 weeks |
| IMTooltip Intramuscular or SC injection | Estradiol cypionate | 1 mg 1x/3–4 weeks | 3 mg 1x/3–4 weeks | 5 mg 1x/3–4 weeks |
| IMTooltip Intramuscular or SC injection | Estradiol benzoate | 0.5 mg 1x/week | 1 mg 1x/week | 1.5 mg 1x/week |
| SC implant | Estradiol | 25 mg 1x/6 months | 50 mg 1x/6 months | 100 mg 1x/6 months |
| Footnotes: $^a$ = No longer used or recommended, due to health concerns. $^b$ = As a single patch applied once or twice per week (worn for 3–4 days or 7 days), depending on the formulation. Note: Dosages are not necessarily equivalent. Sources: See template. |||||

### Available forms

Estropipate was available in the form of 0.75, 1.5, 3, and 6 mg oral tablets and 1.5 mg/gram vaginal cream. Estropipate is no longer available in the United States.

## Pharmacology
### Pharmacodynamics

Estropipate is a prodrug of estrone and estradiol. Hence, it is an estrogen, or an agonist of the estrogen receptors.
vte Relative oral potencies of estrogens :
| Estrogen | HFTooltip Hot flashes | VETooltip Vaginal epithelium | UCaTooltip Urinary calcium | FSHTooltip Follicle-stimulating hormone | LHTooltip Luteinizing hormone | HDLTooltip High-density lipoprotein-CTooltip Cholesterol | SHBGTooltip Sex hormone-binding globulin | CBGTooltip Corticosteroid-binding globulin | AGTTooltip Angiotensinogen | Liver |
| Estradiol | 1.0 | 1.0 | 1.0 | 1.0 | 1.0 | 1.0 | 1.0 | 1.0 | 1.0 | 1.0 |
| Estrone | ? | ? | ? | 0.3 | 0.3 | ? | ? | ? | ? | ? |
| Estriol | 0.3 | 0.3 | 0.1 | 0.3 | 0.3 | 0.2 | ? | ? | ? | 0.67 |
| Estrone sulfate | ? | 0.9 | 0.9 | 0.8–0.9 | 0.9 | 0.5 | 0.9 | 0.5–0.7 | 1.4–1.5 | 0.56–1.7 |
| Conjugated estrogens | 1.2 | 1.5 | 2.0 | 1.1–1.3 | 1.0 | 1.5 | 3.0–3.2 | 1.3–1.5 | 5.0 | 1.3–4.5 |
| Equilin sulfate | ? | ? | 1.0 | ? | ? | 6.0 | 7.5 | 6.0 | 7.5 | ? |
| Ethinylestradiol | 120 | 150 | 400 | 60–150 | 100 | 400 | 500–600 | 500–600 | 350 | 2.9–5.0 |
| Diethylstilbestrol | ? | ? | ? | 2.9–3.4 | ? | ? | 26–28 | 25–37 | 20 | 5.7–7.5 |
| Sources and footnotes Notes: Values are ratios, with estradiol as standard (i.e., 1.0). Abbreviations: HF = Clinical relief of hot flashes. VE = Increased proliferation of vaginal epithelium. UCa = Decrease in UCaTooltip urinary calcium. FSH = Suppression of FSHTooltip follicle-stimulating hormone levels. LH = Suppression of LHTooltip luteinizing hormone levels. HDL-C, SHBG, CBG, and AGT = Increase in the serum levels of these liver proteins. Liver = Ratio of liver estrogenic effects to general/systemic estrogenic effects (hot flashes/gonadotropins). Sources: See template. |||||||||||

### Pharmacokinetics

Estropipate is hydrolyzed into estrone in the body. Estrone can then be transformed into estradiol by 17β-hydroxysteroid dehydrogenase.

## History

Estropipate was introduced for medical use by Abbott in 1968. It was approved by the FDATooltip Food and Drug Administration in the United States in 1991.

## Society and culture
### Generic names

Estropipate is the generic name of the drug and its INNTooltip International Nonproprietary Name, USANTooltip United States Adopted Name, and BANTooltip British Approved Name.

### Brand names

Estropipate was marketed under the brand names Genoral, Harmogen, Improvera, Ogen, Ortho-Est, and Sulestrex among others.

### Availability

Estropipate has been discontinued in the United States. In the past, estropipate has also been marketed in Canada, the United Kingdom, Ireland, Switzerland, Australia, South Africa, Mexico, and Indonesia.