# Norgestrel

Norgestrel, sold under the brand name Opill among others, is a progestin which is used in birth control pills. It is often combined with the estrogen ethinylestradiol, marketed as Ovral. It is also used in menopausal hormone therapy. It is taken by mouth.
Side effects of norgestrel include menstrual irregularities, headaches, nausea, and breast tenderness. The most common side effects of the norgestrel include irregular bleeding, headaches, dizziness, nausea, increased appetite, abdominal pain, cramps, or bloating. Norgestrel is a progestin, or a synthetic progestogen, and hence is an agonist of the progesterone receptor, the biological target of progestogens like progesterone. It has weak androgenic activity and no other important hormonal activity.
Norgestrel was patented in 1961 and came into medical use, specifically in birth control pills, in 1966. It was subsequently introduced for use in menopausal hormone therapy as well. Norgestrel is sometimes referred to as a "second-generation" progestin. It is marketed widely throughout the world. Norgestrel is available as a generic medication. In 2022, the version with ethinylestradiol was the 264th most commonly prescribed medication in the United States, with more than 1 million prescriptions. In July 2023, the US Food and Drug Administration (FDA) approved norgestrel for over-the-counter sale.

## Medical uses

Norgestrel is used in combination with ethinylestradiol or quinestrol in combined birth control pills, alone in progestogen-only birth control pills, and in combination with estradiol or conjugated estrogens in menopausal hormone therapy. It has also been used as an emergency contraceptive in the Yuzpe regimen.

## Pharmacology
### Pharmacodynamics

Norgestrel is a progestogen, or an agonist of the progesterone receptor. The biological activity of norgestrel lies in the levo enantiomer, levonorgestrel, whereas the dextro isomer is inactive. As such, norgestrel is identical in its hormonal activity to levonorgestrel except that it is half as potent by weight. Levonorgestrel, and by extension norgestrel, have some androgenic activity, but no estrogenic, antimineralocorticoid, or glucocorticoid activity.
vte Relative affinities (%) of levonorgestrel and metabolites :
| Compound | PRTooltip Progesterone receptor | ARTooltip Androgen receptor | ERTooltip Estrogen receptor | GRTooltip Glucocorticoid receptor | MRTooltip Mineralocorticoid receptor | SHBGTooltip Sex hormone-binding globulin | CBGTooltip Corticosteroid binding globulin |
| Levonorgestrel | 150–162 | 34$^a$, 45 | 0 | 1–8 | 17–75 | 50 | 0 |
| 5α-Dihydrolevonorgestrel | 50 | 38$^a$ | 0 | ? | ? | ? | ? |
| 3α,5α-Tetrahydrolevonorgestrel | ? | ? | 0.4 | ? | ? | ? | ? |
| 3β,5α-Tetrahydrolevonorgestrel | ? | ? | 2.4 | ? | ? | ? | ? |
| Notes: Values are percentages (%). Reference ligands (100%) were promegestone for the PRTooltip progesterone receptor, metribolone ($^a$ = mibolerone) for the ARTooltip androgen receptor, E2 for the ERTooltip estrogen receptor, DEXATooltip dexamethasone for the GRTooltip glucocorticoid receptor, aldosterone for the MRTooltip mineralocorticoid receptor, DHTTooltip dihydrotestosterone for SHBGTooltip sex hormone-binding globulin, and cortisol for CBGTooltip Corticosteroid-binding globulin. Sources: See template. ||||||||
The ovulation-inhibiting dose of norgestrel appears to be greater than 75 μg/day, as ovulation occurred in 50 to 75% of cycles with this dosage of norgestrel in studies. The ovulation-inhibiting dosage of levonorgestrel, which is twice as potent as norgestrel, is approximately 50 to 60 μg/day. One review lists the ovulation-inhibiting dose of norgestrel as 100 μg/day. The endometrial transformation dose of norgestrel is listed as 12 mg per cycle and the menstrual delay test dose of norgestrel is listed as 0.5 to 2 mg/day.

### Pharmacokinetics

The pharmacokinetics of norgestrel have been reviewed.

## Chemistry

Norgestrel, also known as rac-13-ethyl-17α-ethynyl-19-nortestosterone or as rac-13-ethyl-17α-ethynylestr-4-en-17β-ol-3-one, is a synthetic estrane steroid and a derivative of testosterone. It is a racemic mixture of stereoisomers dextronorgestrel (the C13α isomer; l-norgestrel, L-norgestrel, or (+)-norgestrel) and levonorgestrel (the C13β isomer; d-norgestrel, D-norgestrel, or (–)-norgestrel), the former of which is inactive (making norgestrel exactly half as potent as levonorgestrel). Norgestrel is more specifically a derivative of norethisterone (17α-ethynyl-19-nortestosterone) and is a member of the gonane (18-methylestrane) subgroup of the 19-nortestosterone family of progestins.

### Synthesis

Chemical syntheses of norgestrel have been published.

## History

Norgestrel was first introduced, as a birth control pill in combination with ethinylestradiol, under the brand name Eugynon in Germany in 1966. It was subsequently marketed as a combined birth control pill with ethinylestradiol in the United States under the brand name Ovral in 1968, and was marketed in many other countries as well.
The contraceptive efficacy of norgestrel was established in the U.S. with the original approval for prescription use in 1973.
In July 2023, the FDA approved norgestrel for over-the-counter sale. The FDA granted the approval to Laboratoire HRA Pharma which was acquired by Perrigo Company plc.

## Society and culture
### Generic names

Norgestrel is the generic name of the drug and its international nonproprietary name, United States Adopted Name, United States Pharmacopeia, British Approved Name, Dénomination Commune Française, Denominazione Comune Italiana, and Japanese Accepted Name. It is also known as dl-norgestrel, DL-norgestrel, or (±)-norgestrel.

### Brand names

Norgestrel is marketed under a variety of brand names including Cyclacur, Cryselle, Cyclo-Progynova, Duoluton, Elinest, Eugynon, Microgynon, Lo/Ovral, Low-Ogestrel, Logynon, Microlut, Minicon, Nordette, Neogest, Opill, Ogestrel, Ovral, Ovran, Ovranette, Ovrette, Planovar, Prempak, Progyluton, and Trinordiol among others.