Krimson 35 is the most commonly prescribed “PCOS pill” in India. It is also the same molecule that France suspended in 2013 after recorded deaths, the European Medicines Agency restricted later that year, and most modern PCOS guidelines now place behind safer alternatives. Indian women are not being told this.
Short answer: Krimson 35 (cyproterone acetate 2 mg + ethinyl estradiol 35 mcg) is effective for severe androgenic symptoms in PCOS but carries roughly 1.5 to 2 times the venous thromboembolism risk of standard combined oral contraceptives, was restricted in Europe in 2013, and remains over-prescribed as a first-line PCOS drug in India without proper risk screening. If you have any clotting risk factor — smoking, migraine with aura, family history of DVT, age above 35, obesity — ask your doctor for a different pill or for spironolactone instead.
This article is the long version. For the broader PCOS picture and where this drug sits in the treatment ladder, start with the PCOS pillar guide. For dermatology-side specifics on hormonal acne treatment including spironolactone, see the PCOS acne deep-dive.
What Krimson 35 Actually Is
Krimson 35 is the most popular Indian brand of the combination cyproterone acetate 2 mg + ethinyl estradiol 35 mcg. The same molecule is sold internationally as Diane 35 (Bayer), and in India under multiple brand names:
- Krimson 35 (Eris Lifesciences)
- Diane 35 (imported)
- Ginette 35
- Crisanta
- Saheli (generic)
- Dianette
Cyproterone acetate is a progestin and an androgen-receptor blocker. The androgen-blocking action is why it works so well for hormonal acne, hirsutism and oily skin — it cuts androgen signalling at the receptor level. The ethinyl estradiol contributes the contraceptive effect, cycle control, and the venous thromboembolism risk that defines the drug’s safety profile.
In therapeutic dose, cyproterone is the most potent oral anti-androgen widely available in India. That is why it works. It is also why the safety questions are real.
The Regulatory History — What Europe Did, and Why
2007 — French ANSM concerns
The French national medicines regulator (Agence Nationale de Sécurité du Médicament, ANSM) began collecting case reports of venous thromboembolism on Diane 35 in women using it as a contraceptive (an off-label use in France).
2012 — French Senate inquiry
After a series of deaths in young women — at least 4 documented thromboembolic deaths and 125 serious adverse events traced to Diane 35 according to French ANSM data — the French Senate opened a formal inquiry. The drug’s risk-benefit profile when used outside the strict androgenic-skin-disease indication came under scrutiny.
January 2013 — France suspends Diane 35
ANSM announced suspension of Diane 35 and its generics. The decision triggered an EU-wide review.
May 2013 — European Medicines Agency review concludes
EMA’s Pharmacovigilance Risk Assessment Committee (PRAC) confirmed that the benefits of Diane 35 outweighed the risks only when used for moderate to severe acne and hirsutism related to androgen sensitivity, after other treatments have failed. The committee specifically restricted use as a contraceptive in isolation, restricted use for mild androgenic disease, and recommended the shortest necessary duration of treatment with periodic review.
Since 2013
The EMA position has held. Health Canada issued a similar warning in 2013. The UK MHRA followed EMA. Australia’s TGA reviewed and tightened indications. The American FDA never approved cyproterone acetate, so the question is moot in the US.
India — no equivalent action
The Central Drugs Standard Control Organisation (CDSCO / DCGI) has not issued an equivalent restriction. Cyproterone acetate plus ethinyl estradiol remains a freely available, routinely prescribed first-line PCOS option in India. Patient leaflets in Indian-marketed packs do list contraindications and warnings, but the structural restriction on indication and duration that EMA imposed has not been adopted.
This is the prescribing gap. It is not that the drug is “banned” — it is that the international risk-benefit reframing has not reached Indian gynaecology in any organised way.
What the Pharmacoepidemiology Actually Shows
Large studies on combined oral contraceptive thromboembolism risk consistently rank cyproterone acetate + EE in a higher-risk tier than levonorgestrel + EE pills (the second-generation standard).
| Pill type | Approximate VTE rate per 10,000 women-years |
|---|---|
| No hormonal contraception, healthy women | 2 to 4 |
| Pregnancy (for reference) | 20 to 30 |
| Postpartum (first 12 weeks, for reference) | 40 to 65 |
| Levonorgestrel + EE 30 mcg (e.g., Mala-N reference equivalent) | 5 to 7 |
| Drospirenone + EE 30 mcg (Yasmin) | 9 to 12 |
| Drospirenone + EE 20 mcg (Yaz) | 8 to 10 |
| Desogestrel + EE 30 mcg (Femilon, Novelon) | 8 to 10 |
| Cyproterone acetate + EE 35 mcg (Krimson 35) | 9 to 12 |
These numbers come from meta-analyses (Lidegaard et al., BMJ; van Hylckama Vlieg et al., BMJ) and large insurance-claim cohorts (Dinger et al.). Numbers vary across studies by definition and population, but the ordinal ranking is consistent.
The headline interpretation: the absolute risk on any combined pill in a healthy young woman is still small. The relative risk on cyproterone-containing pills versus levonorgestrel pills is roughly 1.5 to 2x. In a 28-year-old non-smoker without other risk factors, the absolute event rate is roughly 1 in 1,000 women per year. In a 36-year-old smoker with a BMI of 31 and migraine with aura, that number rises sharply.
The point of risk-stratification is to identify who should not take the drug at all. In Indian practice, that conversation rarely happens.
Who Should Never Take Krimson 35 (Absolute Contraindications)
If you have any of these, do not take Krimson 35 or any other combined oral contraceptive:
- Personal history of deep vein thrombosis, pulmonary embolism, stroke, heart attack, or transient ischaemic attack
- Known inherited thrombophilia (Factor V Leiden, prothrombin G20210A, protein C / S / antithrombin deficiency, antiphospholipid antibody syndrome)
- Migraine with aura
- Active or suspected breast cancer or other oestrogen-dependent malignancy
- Severe hypertension (BP above 160/100 despite treatment)
- Severe liver disease, current or recent acute hepatitis, liver tumours
- Active gallbladder disease
- Undiagnosed vaginal bleeding
- Pregnancy or possible pregnancy
- Within 6 weeks postpartum if breastfeeding (4 weeks if not breastfeeding)
- Major surgery with prolonged immobilisation in the next 4 weeks
Strong Relative Contraindications
Discuss the risk-benefit carefully and prefer alternatives if you have:
- Smoking at any age (the combination of smoking + combined pill multiplies arterial risk dramatically; smoking + combined pill above age 35 is an absolute contraindication)
- Age above 35
- BMI above 30
- Diabetes with vascular complications
- Controlled hypertension on medication
- Family history of unprovoked venous thrombosis before age 50 in a first-degree relative
- Migraine without aura (relative — discuss)
- Prolonged immobilisation expected (long flights, post-surgical recovery, fractures)
- History of severe depression on previous hormonal contraception
- Gallbladder disease history
- Sickle cell disease
The Indian Prescribing Gap — What’s Going Wrong
A typical Indian PCOS visit:
- Patient describes irregular periods and acne
- Pelvic ultrasound shows multifollicular ovaries
- Gynaecologist writes Krimson 35
- No bloodwork
- No risk-factor screen for clotting
- No discussion of indication or duration
- No follow-up scheduled
- Patient stays on the pill for 3 to 7 years
Each step is a deviation from international guidance. The patient is given a powerful anti-androgen pill in a higher-risk class without subtype evaluation, without risk-stratification, and without a planned exit. The result is a generation of Indian women on Krimson 35 who would have been switched to spironolactone or a drospirenone pill in any modern European or American clinic.
The fix is not banning the drug. The fix is restricting it to the patients in whom the benefits genuinely outweigh the risks — moderate to severe androgenic skin disease unresponsive to alternatives, short-duration use, periodic review, exclusion of clotting risk factors.
Safer Indian Alternatives (Brand by Brand)
For acne, hirsutism, oily skin (the main reasons Krimson 35 is prescribed)
Spironolactone (Aldactone, Spiractin, Spirono)
- Mechanism: oral anti-androgen, blocks androgen receptor
- Dose: 50 to 100 mg daily, can titrate to 200 mg
- Cost: Rs 85 to 140 per month
- Pros: cheap, effective for acne and hirsutism, no oestrogen burden, mildly diuretic (helps with bloating)
- Cons: teratogenic (must use reliable contraception), mild diuresis, occasional menstrual irregularity, monitor potassium
- See PCOS acne and spironolactone deep-dive
Drospirenone-containing combined OCPs
- Brands: Yaz (drospirenone 3 mg + EE 20 mcg), Yasmin (drospirenone 3 mg + EE 30 mcg), Dronis (Indian brand), Krimson Plus
- Mechanism: progestin with anti-androgen action, suppresses ovarian androgen production
- Cost: Rs 450 to 620 per cycle
- Pros: lower thromboembolism risk than cyproterone pills, anti-androgen, mild diuretic effect
- Cons: still a combined pill — same contraindication list as Krimson 35 (just lower risk magnitude)
Desogestrel or norethindrone-containing combined OCPs
- Brands: Femilon, Novelon (desogestrel + EE), Ovral L (levonorgestrel reference)
- Mechanism: standard combined pill, less anti-androgen punch than cyproterone or drospirenone
- Cost: Rs 90 to 250 per cycle
- Pros: lower thromboembolism risk than cyproterone, decades of safety data, cheap
- Cons: less effective for androgenic skin disease — best for cycle regulation rather than severe acne or hirsutism
Topical and procedural alternatives for hirsutism
- Eflornithine cream (Vaniqa) for facial hirsutism — slows hair growth, no systemic effect
- Laser hair reduction — 6 sessions, Rs 18,000 to 42,000 for full face, see the PCOS pillar cost section
- Electrolysis for isolated hairs
For cycle regulation (if no contraception is needed)
Cyclical progesterone
- Brands: Susten (micronised progesterone), Naturogest, Crinone gel
- Dose: 200 to 400 mg at night for 10 days every 60 to 90 days
- Cost: Rs 200 to 600 per cycle
- Mechanism: induces a withdrawal bleed, protects endometrium from unopposed oestrogen
- Pros: no thromboembolism risk, can be used in women with absolute contraindications to combined pills
- Cons: not contraceptive, requires planned cycles, does not address acne or hirsutism
For insulin resistance (the underlying driver in most cases)
- Metformin 500 mg twice or thrice daily, Rs 120 to 180 per month
- Myo-inositol + D-chiro-inositol 40:1 combination, Rs 650 to 1,800 per month
- Lifestyle, post-meal walking, strength training (covered in the PCOS pillar)
Many Indian women on Krimson 35 would benefit more from a metabolic-first approach with spironolactone added for the skin symptoms — and might not need a combined pill at all.
The Decision Matrix — Should You Be on Krimson 35?
Use this as a starting point for a conversation with your doctor.
| Your situation | Krimson 35 is appropriate? | Better option |
|---|---|---|
| Mild acne, regular cycles | No | Topical retinoid, spironolactone if needed |
| Moderate acne, irregular cycles, no clotting risk factors | Possibly, short-term | Drospirenone OCP + spironolactone often equivalent |
| Severe cystic acne + hirsutism unresponsive to other treatments, no clotting risk | Yes, with periodic review | Same |
| Need contraception + PCOS, no clotting risk | No | Drospirenone or desogestrel OCP |
| Insulin resistance dominant + central weight gain | No | Metformin + inositol + lifestyle |
| Lean PCOS, adrenal subtype | No | Lifestyle + adrenal-subtype protocol |
| Smoker | No | Spironolactone alone |
| Age above 35 | No | Spironolactone alone, drospirenone if non-smoker |
| Migraine with aura | No (contraindicated) | Spironolactone, progesterone, lifestyle |
| Family history of DVT | No (relative contraindication) | Spironolactone, drospirenone with screening |
| BMI above 30 | Possibly, with caution | Address weight first; drospirenone with caution |
The Conversation Script
Print this. Hand it to your gynaecologist or endocrinologist.
“I would like to discuss whether Krimson 35 is the right choice for my PCOS treatment, or whether I should be on an alternative. Specifically:
- Which symptom is the prescription targeting — acne, hirsutism, cycle regulation, contraception, or a combination?
- Have I been screened for the absolute and relative contraindications to combined oral contraceptives, including personal and family clotting history, migraine with aura, smoking status, blood pressure, BMI and liver function?
- Is the underlying insulin resistance being treated separately, or is the Krimson 35 the entire plan?
- What is the planned duration of treatment, and what is the planned exit strategy?
- Given the European Medicines Agency 2013 restriction on cyproterone-containing pills to severe androgenic skin disease unresponsive to other treatments, do my symptoms meet that threshold, or would a drospirenone-containing pill, a desogestrel pill, or oral spironolactone with cyclical progesterone be a safer alternative for my profile?
- If we proceed with Krimson 35, when will we review and reconsider?”
A clinician who declines to engage with these questions is signalling that they are prescribing on autopilot. That is not the right partner for a YMYL condition you may need to manage for 20 years.
How to Switch Off Krimson 35 Safely
If you and your doctor decide to stop or switch, the practical sequence is:
- Do not stop mid-pack. Finish the current pack to avoid breakthrough bleeding.
- Plan the switch. If you are moving to a drospirenone or desogestrel OCP, start the new pill the day after finishing Krimson 35 — no gap.
- If switching to spironolactone alone, start spironolactone the day after the last Krimson 35 pill. Use barrier contraception during the first 2 weeks while ovulation regularises. Spironolactone is teratogenic, so reliable contraception is non-negotiable.
- If stopping all hormonal treatment, expect cycles to be irregular for 3 to 6 months. Track basal body temperature and cervical mucus to monitor return of ovulation. Use barrier contraception.
- Expect a temporary acne or oily-skin flare in months 2 to 4 as androgen suppression unwinds. Topical adapalene plus benzoyl peroxide, plus spironolactone if needed, manages this.
- Re-test the PCOS hormone and metabolic panel after 3 months off Krimson 35 to get a true baseline (see PCOS tests to demand).
- Re-evaluate the PCOS subtype and rebuild a protocol around the actual drivers.
What to Watch For While You Are Still on Krimson 35
Stop the medication and seek immediate medical attention if you develop any of:
- Sudden severe headache or the worst headache of your life
- Vision changes, especially loss of vision in one eye
- Slurred speech, one-sided weakness, numbness or facial drooping
- Chest pain, sudden shortness of breath, cough with blood
- Unilateral leg pain or swelling, especially calf
- Severe abdominal pain
- Yellowing of skin or eyes
- New persistent severe migraine with aura
- Breast lump
These are warning signs of stroke, pulmonary embolism, deep vein thrombosis, mesenteric thrombosis or liver injury. They are rare in absolute terms. They are not so rare that they should not be drilled into every Krimson 35 patient.
What This Article Is Not
It is not an argument that Krimson 35 should be banned, or that every woman currently on it should stop. The drug genuinely works for severe androgenic skin disease that has resisted other treatments. For some patients, after proper risk screening, it remains a reasonable choice.
What this article is, is a correction to the default prescribing pattern in India, where Krimson 35 is handed out as the first-line PCOS pill without subtype evaluation, without risk screening, without indication review, and without a planned exit. That default pattern is downstream of regulatory inaction, clinical training inertia, and patient underinformation. Each of those is fixable. The first step is knowing the drug you are taking and asking the questions your prescriber should already be asking.
Sources & References
- European Medicines Agency (EMA), Pharmacovigilance Risk Assessment Committee. Review of cyproterone acetate / ethinylestradiol (Diane 35 and generics). 2013.
- Agence Nationale de Sécurité du Médicament et des Produits de Santé (ANSM), France. Suspension of Diane 35 and generics. January 2013.
- Lidegaard Ø et al. Risk of venous thromboembolism from use of oral contraceptives containing different progestogens and oestrogen doses: Danish cohort study, 2001-9. BMJ 2011; 343:d6423.
- van Hylckama Vlieg A et al. The venous thrombotic risk of oral contraceptives, effects of oestrogen dose and progestogen type: results of the MEGA case-control study. BMJ 2009; 339:b2921.
- Dinger JC et al. The safety of a drospirenone-containing oral contraceptive: final results from the European Active Surveillance Study on oral contraceptives. Contraception, 2007.
- Endocrine Society Clinical Practice Guideline: Diagnosis and Treatment of Polycystic Ovary Syndrome.
- Teede HJ et al. Recommendations from the 2023 International Evidence-based Guideline for the Assessment and Management of Polycystic Ovary Syndrome.
- World Health Organization. Medical eligibility criteria for contraceptive use, latest edition.
- Faculty of Sexual and Reproductive Healthcare (FSRH), UK. Clinical guidance on combined hormonal contraception.
Medical disclaimer: This article is educational and reviewed against international PCOS and contraception guidelines as of 2026. It is not a substitute for individualised medical advice. Do not stop or switch any prescription medication without consulting a qualified clinician. If you are currently on Krimson 35 and have concerns, schedule a review — do not abrupt-stop mid-pack. PCOS and combined hormonal contraception are YMYL topics; verify any decision with a qualified gynaecologist, endocrinologist or reproductive endocrinologist.