Mestranol and Norethindrone

Mestranol and Norethindrone Brand Names

Necon 1/50 | Norinyl 1/50 | Ortho-Novum 1/50

What is Mestranol and Norethindrone

Mestranol and norethindrone are used together as an oral contraceptive agent for routine contraception.

Mestranol is the estrogen that was in the first marketed combination oral contraceptive pill, Enovid. Mestranol is metabolized to ethinyl estradiol, the active form in vivo.

Norethindrone is a first generation oral progestin with moderate androgenic and slight estrogenic activity relative to newer progestins.

Norethindrone is known as norethisterone outside of the United States. Combined hormonal contraceptives can be used in female patients from menarche to over the age of 40 years up until the time of menopause with proper selection of products.

The choice of a routine hormonal contraceptive for any given patient is based on the individual’s contraceptive needs, underlying medical conditions or risk factors for adverse effects, and individual preferences for use.

All combined oral contraceptives (COCs) have risks related to venous and arterial thromboembolism, particularly in women who smoke; all combined hormonal contraceptive labels contain a boxed warning about tobacco smoking.

The Centers for Disease Control’s U.S. medical Eligibility Criteria describe considerations for risk vs. benefits, including medical conditions or attributes that contraindicate use; these criteria can help prescribing practitioners in product selection for individual patients.

Mestranol and norethindrone oral contraceptive combinations were first approved by the FDA before 1982.

Indications

1. acne vulgaris
2. amenorrhea
3. contraception
4. dysfunctional uterine bleeding
5. endometriosis
6. gastrointestinal bleeding prophylaxis
7. hirsutism
8. polycystic ovary syndrome

Side Effects

1. abdominal pain
2. acne vulgaris
3. alopecia
4. amenorrhea
5. anaphylactoid reactions
6. angioedema
7. anorexia
8. anxiety
9. appetite stimulation
10. arthralgia
11. asthenia
12. back pain
13. bowel ischemia
14. breakthrough bleeding
15. breast discharge
16. breast enlargement
17. candidiasis
18. cataracts
19. cervical dysplasia
20. cholecystitis
21. cholelithiasis
22. cholestasis
23. colitis
24. cystitis
25. depression
26. diarrhea
27. diplopia
28. dysmenorrhea
29. dyspepsia
30. edema
31. elevated hepatic enzymes
32. emotional lability
33. erythema multiforme
34. erythema nodosum
35. fatigue
36. fluid retention
37. galactorrhea
38. gingivitis
39. headache
40. hepatitis
41. hepatoma
42. hirsutism
43. hyperlipidemia
44. hypertension
45. hypertriglyceridemia
46. intracranial bleeding
47. irritability
48. jaundice
49. lactation suppression
50. leukorrhea
51. libido decrease
52. libido increase
53. lupus-like symptoms
54. maculopapular rash
55. mastalgia
56. melasma
57. menorrhagia
58. menstrual irregularity
59. migraine
60. musculoskeletal pain
61. myalgia
62. myocardial infarction
63. nausea
64. new primary malignancy
65. optic neuritis
66. pancreatitis
67. papilledema
68. peliosis hepatis
69. pelvic pain
70. photosensitivity
71. porphyria
72. pruritus
73. pulmonary embolism
74. rash
75. retinal thrombosis
76. rhinitis
77. sinusitis
78. stroke
79. thromboembolism
80. thrombosis
81. urticaria
82. vaginal discharge
83. vaginal irritation
84. vaginitis
85. visual impairment
86. vomiting
87. weight gain
88. weight loss

Monitoring Parameters

• pap smear
• pelvic exam

Contraindications

• acquired immunodeficiency syndrome (AIDS)
• atrial fibrillation
• breast cancer
• breast-feeding
• cerebrovascular disease
• cervical cancer
• children
• chloasma
• cholestasis
• contact lenses
• coronary artery disease
• coronary thrombosis
• depression
• diabetes mellitus
• endocarditis
• endometrial cancer
• gallbladder disease
• glaucoma
• headache
• hepatic disease
• hepatitis
• hepatocellular cancer
• hereditary angioedema
• history of angioedema
• human immunodeficiency virus (HIV) infection
• hypercalcemia
• hypercholesterolemia
• hyperlipidemia
• hypertension
• hypertriglyceridemia
• hypothyroidism
• jaundice
• migraine
• myocardial infarction
• obesity
• obstetric delivery
• ovarian cancer
• porphyria
• pregnancy
• protein C deficiency
• protein S deficiency
• renal disease
• stroke
• surgery
• systemic lupus erythematosus (SLE)
• thromboembolic disease
• thromboembolism
• thrombophlebitis
• thyroid disease
• tobacco smoking
• uterine cancer
• vaginal bleeding
• vaginal cancer
• valvular heart disease
• visual disturbance

Interactions

• Acarbose
• Acebutolol
• Acetaminophen; Aspirin, ASA; Caffeine
• Acetaminophen; Butalbital
• Acetaminophen; Butalbital; Caffeine
• Acetaminophen; Butalbital; Caffeine; Codeine
• Acetaminophen; Caffeine
• Acetaminophen; Caffeine; Dihydrocodeine
• Acetaminophen; Caffeine; Magnesium Salicylate; Phenyltoloxamine
• Acetaminophen; Caffeine; Phenyltoloxamine; Salicylamide
• Acetaminophen; Propoxyphene
• Acetohexamide
• Acitretin
• Albiglutide
• Aliskiren
• Aliskiren; Amlodipine
• Aliskiren; Amlodipine; Hydrochlorothiazide, HCTZ
• Aliskiren; Hydrochlorothiazide, HCTZ
• Aliskiren; Valsartan
• Alogliptin
• Alogliptin; Metformin
• Alogliptin; Pioglitazone
• Alpha-blockers
• Alpha-glucosidase Inhibitors
• Alprazolam
• Amikacin
• Amiloride
• Amiloride; Hydrochlorothiazide, HCTZ
• Aminoglycosides
• Amiodarone
• Amitriptyline; Chlordiazepoxide
• Amlodipine
• Amlodipine; Atorvastatin
• Amlodipine; Benazepril
• Amlodipine; Celecoxib
• Amlodipine; Hydrochlorothiazide, HCTZ; Olmesartan
• Amlodipine; Hydrochlorothiazide, HCTZ; Valsartan
• Amlodipine; Olmesartan
• Amlodipine; Telmisartan
• Amlodipine; Valsartan
• Amobarbital
• Amoxicillin
• Amoxicillin; Clarithromycin; Lansoprazole
• Amoxicillin; Clarithromycin; Omeprazole
• Amoxicillin; Clavulanic Acid
• Ampicillin
• Ampicillin; Sulbactam
• Amprenavir
• Anastrozole
• Angiotensin II receptor antagonists
• Angiotensin-converting enzyme inhibitors
• Apalutamide
• Aprepitant, Fosaprepitant
• Armodafinil
• Artemether; Lumefantrine
• Aspirin, ASA; Butalbital; Caffeine
• Aspirin, ASA; Butalbital; Caffeine; Codeine
• Aspirin, ASA; Caffeine; Dihydrocodeine
• Aspirin, ASA; Caffeine; Orphenadrine
• Atazanavir
• Atazanavir; Cobicistat
• Atenolol
• Atenolol; Chlorthalidone
• Atorvastatin
• Atorvastatin; Ezetimibe
• Atropine; Hyoscyamine; Phenobarbital; Scopolamine
• Azelastine; Fluticasone
• Azilsartan
• Azilsartan; Chlorthalidone
• Azithromycin
• Aztreonam
• Bacitracin
• Barbiturates
• Beclomethasone
• Belladonna Alkaloids; Ergotamine; Phenobarbital
• Benazepril
• Benazepril; Hydrochlorothiazide, HCTZ
• Bendroflumethiazide; Nadolol
• Beta-adrenergic blockers
• Betamethasone
• Betaxolol
• Bexarotene
• Bismuth Subcitrate Potassium; Metronidazole; Tetracycline
• Bismuth Subsalicylate; Metronidazole; Tetracycline
• Bisoprolol
• Bisoprolol; Hydrochlorothiazide, HCTZ
• Boceprevir
• Bosentan
• Brigatinib
• Brimonidine; Timolol
• Bromocriptine
• Budesonide
• Budesonide; Formoterol
• Bumetanide
• Butabarbital
• Caffeine
• Caffeine; Ergotamine
• Calaspargase pegol
• Calcium
• Calcium-channel blockers
• Canagliflozin
• Canagliflozin; Metformin
• Candesartan
• Candesartan; Hydrochlorothiazide, HCTZ
• Captopril
• Captopril; Hydrochlorothiazide, HCTZ
• Carbamazepine
• Carbapenems
• Carbenicillin
• Carteolol
• Carvedilol
• Cefaclor
• Cefadroxil
• Cefazolin
• Cefdinir
• Cefditoren
• Cefepime
• Cefiderocol
• Cefixime
• Cefotaxime
• Cefotetan
• Cefoxitin
• Cefpodoxime
• Cefprozil
• Ceftaroline
• Ceftazidime
• Ceftazidime; Avibactam
• Ceftibuten
• Ceftizoxime
• Ceftolozane; Tazobactam
• Ceftriaxone
• Cefuroxime
• Cenobamate
• Central-acting adrenergic agents
• Cephalexin
• Charcoal
• Chenodiol
• Chloramphenicol
• Chlordiazepoxide
• Chlordiazepoxide; Clidinium
• Chlorothiazide
• Chlorpropamide
• Chlorthalidone
• Chlorthalidone; Clonidine
• Ciclesonide
• Cimetidine
• Ciprofloxacin
• Clarithromycin
• Clevidipine
• Clindamycin
• Clobazam
• Clonazepam
• Clonidine
• Clorazepate
• Cobicistat
• Colesevelam
• Colistimethate, Colistin, Polymyxin E
• Corticosteroids
• Cortisone
• Cosyntropin
• Cyclosporine
• Dabrafenib
• Dalbavancin
• Dantrolene
• Dapagliflozin
• Dapagliflozin; Metformin
• Dapagliflozin; Saxagliptin
• Daptomycin
• Daratumumab; Hyaluronidase
• Darunavir
• Darunavir; Cobicistat
• Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide
• Dasabuvir; Ombitasvir; Paritaprevir; Ritonavir
• Deferasirox
• Deflazacort
• Delafloxacin
• Demeclocycline
• Dexamethasone
• Diazepam
• Dicloxacillin
• Diltiazem
• Dipeptidyl Peptidase-4 Inhibitors
• Dirithromycin
• Doripenem
• Dorzolamide; Timolol
• Doxazosin
• Doxycycline
• Dronedarone
• Dulaglutide
• Duloxetine
• Efavirenz
• Efavirenz; Emtricitabine; Tenofovir
• Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate
• Elagolix
• Elagolix; Estradiol; Norethindrone acetate
• Elvitegravir
• Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide
• Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate
• Empagliflozin
• Empagliflozin; Linagliptin
• Empagliflozin; Linagliptin; Metformin
• Empagliflozin; Metformin
• Enalapril, Enalaprilat
• Enalapril; Felodipine
• Enalapril; Hydrochlorothiazide, HCTZ
• Enasidenib
• Encorafenib
• Enzalutamide
• Eprosartan
• Eprosartan; Hydrochlorothiazide, HCTZ
• Eravacycline
• Ertapenem
• Ertugliflozin
• Ertugliflozin; Metformin
• Ertugliflozin; Sitagliptin
• Erythromycin
• Erythromycin; Sulfisoxazole
• Eslicarbazepine
• Esmolol
• Estazolam
• Ethacrynic Acid
• Exemestane
• Exenatide
• Felbamate
• Felodipine
• Fidaxomicin
• Flibanserin
• Fludrocortisone
• Flunisolide
• Flurazepam
• Fluticasone
• Fluticasone; Salmeterol
• Fluticasone; Umeclidinium; Vilanterol
• Fluticasone; Vilanterol
• Formoterol; Mometasone
• Fosamprenavir
• Fosinopril
• Fosinopril; Hydrochlorothiazide, HCTZ
• Furosemide
• Gemifloxacin
• Gentamicin
• Glimepiride
• Glimepiride; Pioglitazone
• Glimepiride; Rosiglitazone
• Glipizide
• Glipizide; Metformin
• Glyburide
• Glyburide; Metformin
• Glycylcyclines
• grapefruit juice
• Green Tea
• Griseofulvin
• Guanabenz
• Guanfacine
• Hemin
• Hyaluronidase
• Hyaluronidase, Recombinant; Immune Globulin
• Hydantoins
• Hydralazine
• Hydralazine; Hydrochlorothiazide, HCTZ
• Hydralazine; Isosorbide Dinitrate, ISDN
• Hydrochlorothiazide, HCTZ
• Hydrochlorothiazide, HCTZ; Irbesartan
• Hydrochlorothiazide, HCTZ; Lisinopril
• Hydrochlorothiazide, HCTZ; Losartan
• Hydrochlorothiazide, HCTZ; Methyldopa
• Hydrochlorothiazide, HCTZ; Metoprolol
• Hydrochlorothiazide, HCTZ; Moexipril
• Hydrochlorothiazide, HCTZ; Olmesartan
• Hydrochlorothiazide, HCTZ; Propranolol
• Hydrochlorothiazide, HCTZ; Quinapril
• Hydrochlorothiazide, HCTZ; Spironolactone
• Hydrochlorothiazide, HCTZ; Telmisartan
• Hydrochlorothiazide, HCTZ; Triamterene
• Hydrochlorothiazide, HCTZ; Valsartan
• Hydrocortisone
• Icosapent ethyl
• Idelalisib
• Imipenem; Cilastatin
• Imipenem; Cilastatin; Relebactam
• Incretin Mimetics
• Indinavir
• Insulin Degludec; Liraglutide
• Insulin Glargine; Lixisenatide
• Insulins
• Irbesartan
• Isoniazid, INH; Pyrazinamide, PZA; Rifampin
• Isoniazid, INH; Rifampin
• Isotretinoin
• Isradipine
• Ivosidenib
• Kanamycin
• Labetalol
• Lamotrigine
• Lefamulin
• Leflunomide
• Lenalidomide
• Lesinurad
• Lesinurad; Allopurinol
• Letrozole
• Levobetaxolol
• Levobunolol
• Levofloxacin
• Levothyroxine
• Levothyroxine; Liothyronine (Porcine)
• Levothyroxine; Liothyronine (Synthetic)
• Linagliptin
• Linagliptin; Metformin
• Lincomycin
• Lincosamides
• Linezolid
• Liothyronine
• Liraglutide
• Lisinopril
• Lixisenatide
• Lomitapide
• Loop diuretics
• Lopinavir; Ritonavir
• Lorlatinib
• Losartan
• Lumacaftor; Ivacaftor
• Mecamylamine
• Meglitinides
• Melatonin
• Mephobarbital
• Meropenem
• Meropenem; Vaborbactam
• Metformin
• Metformin; Pioglitazone
• Metformin; Repaglinide
• Metformin; Rosiglitazone
• Metformin; Saxagliptin
• Metformin; Sitagliptin
• Methohexital
• Methyclothiazide
• Methyldopa
• Methylprednisolone
• Metolazone
• Metoprolol
• Metreleptin
• Metronidazole
• Metyrapone
• Mifepristone
• Miglitol
• Miltefosine
• Mineral Oil
• Minocycline
• Minoxidil
• Mivacurium
• Modafinil
• Moexipril
• Mometasone
• Morphine
• Morphine; Naltrexone
• Moxifloxacin
• Mycophenolate
• Nadolol
• Nafcillin
• Nebivolol
• Nebivolol; Valsartan
• Nefazodone
• Nelfinavir
• Neomycin
• Nevirapine
• Nicardipine
• Nifedipine
• Nimodipine
• Nisoldipine
• Nitrofurantoin
• Nitroprusside
• Norfloxacin
• Ofloxacin
• Olmesartan
• Omadacycline
• Ombitasvir; Paritaprevir; Ritonavir
• Omeprazole; Amoxicillin; Rifabutin
• Oritavancin
• Ospemifene
• Oxacillin
• Oxazepam
• Oxcarbazepine
• Paromomycin
• Pegaspargase
• Penbutolol
• Penicillin G
• Penicillin G Benzathine
• Penicillin G Benzathine; Penicillin G Procaine
• Penicillin G Procaine
• Penicillin V
• Pentobarbital
• Perindopril
• Perindopril; Amlodipine
• Pexidartinib
• Phenobarbital
• Phenothiazines
• Phenoxybenzamine
• Phentermine; Topiramate
• Phentolamine
• Pindolol
• Piperacillin
• Piperacillin; Tazobactam
• Pitolisant
• Plazomicin
• Polymyxin B
• Polymyxins
• Potassium-sparing diuretics
• Pramlintide
• Prasterone, Dehydroepiandrosterone, DHEA (Dietary Supplements)
• Prasterone, Dehydroepiandrosterone, DHEA (FDA-approved)
• Prazosin
• Prednisolone
• Prednisone
• Primidone
• Propoxyphene
• Propranolol
• Pyrimethamine; Sulfadoxine
• Quazepam
• Quinapril
• Raloxifene
• Ramipril
• Reserpine
• Ribociclib; Letrozole
• Rifabutin
• Rifampin
• Rifamycins
• Rifapentine
• Riluzole
• Ritonavir
• Rituximab; Hyaluronidase
• Rivaroxaban
• Roflumilast
• Romidepsin
• Ropinirole
• Rosuvastatin
• Rufinamide
• Sacubitril; Valsartan
• Saquinavir
• Sarilumab
• Saxagliptin
• Secobarbital
• Selegiline
• Semaglutide
• SGLT2 Inhibitors
• Siltuximab
• Simvastatin; Sitagliptin
• Sincalide
• Sitagliptin
• Somatropin, rh-GH
• Spironolactone
• St. John’s Wort, Hypericum perforatum
• Streptogramins
• Streptomycin
• Succinylcholine
• Sugammadex
• Sulfadiazine
• Sulfamethoxazole; Trimethoprim, SMX-TMP, Cotrimoxazole
• Sulfasalazine
• Sulfisoxazole
• Sulfonamides
• Sulfonylureas
• Tacrine
• Tazemetostat
• Tedizolid
• Telaprevir
• Telavancin
• Telithromycin
• Telmisartan
• Terazosin
• Teriflunomide
• Testolactone
• Tetracycline
• Thalidomide
• Theophylline, Aminophylline
• Thiazide diuretics
• Thiazolidinediones
• Thiopental
• Thyroid hormones
• Ticarcillin
• Ticarcillin; Clavulanic Acid
• Tigecycline
• Timolol
• Tinidazole
• Tipranavir
• Tizanidine
• tobacco
• Tobramycin
• Tocilizumab
• Tolazamide
• Tolbutamide
• Tolvaptan
• Topiramate
• Toremifene
• Torsemide
• Trandolapril
• Trandolapril; Verapamil
• Tranexamic Acid
• Trastuzumab; Hyaluronidase
• Triamcinolone
• Triamterene
• Triazolam
• Tricyclic antidepressants
• Trimethoprim
• Ulipristal
• Ursodeoxycholic Acid, Ursodiol
• Valproic Acid, Divalproex Sodium
• Valsartan
• Vancomycin
• Verapamil
• Voriconazole
• Warfarin

What research says about this combination drug?

• The usefulness of a new oral contraceptive compound containing norethindrone 5 mg. and mestranol 0.075 mg. (Ortho-Novum) was studied.
• One hundred and seventeen private patients used this preparation for a total of 998 menstrual cycles. There were no pregnancies. Side effects were minimal and caused few (11 patients) to discontinue use.
• The most significant of these was weight gain and a premenstrual tension syndrome including nausea, breakthrough bleeding and skin effects.
• Other symptoms were minor and easily controlled. Instruction in use of the preparation is easy. Patient acceptance is excellent. Possible masculinizing effects, liver damage, or harmful effects on the uterus were checked specifically by laboratory evaluation; no significant abnormal findings were noted.

This appears to be an effective oral contraceptive which is well accepted by the patient and which produced no serious side effects as used in this study.

Sources

1.DICKINSON JH, SMITH GG. A new and practical oral contraceptive agent: norethindrone with mestranol. Can Med Assoc J. 1963 Aug 10;89(6):242-5. PMID: 14027723; PMCID: PMC1921561.https://pmc.ncbi.nlm.nih.gov/articles/PMC1921561/