What's in your drug? Deciphering the details of my OC pill

Updated: Mar 23, 2019

Recently I've had a break out of acne. I'm 29 years old but it's as if my body has seen androgens for the first time.


Funnily enough, that's almost true. My body is making androgens again for the first time in a decade. But it's not the first time I've had a break out. I had acne 15 years ago. Oily skin and greasy hair too. Like most teenage girls, I felt really self conscious about my skin, and anxious each time another, glaring pimple formed. So I used a pill to block it. I didn't even think to question the mechanism behind the magic. I understood that the pill could clear up my skin in a matter of months. That was enough for me.


I recently did some research into that pill that I'd been taking for 10 years, Estelle-35. It freaked me out. Here are some things I learned about the pill I put into my body for a decade.



Lesson # 1.  It is an androgen blocker (that I probably didn't need)


Most OC pills combine a synthetic estrogen and a synthetic progesterone (progestin) to suppress the HPO axis and stop ovulation. Each formula is a little different. Estelle-35 is designed to treat conditions that arise due to high androgens, like cystic acne, hirsutism, alopecia or PCOS. To do this, Estelle-35 pairs a synthetic estrogen to a progestin that is also a potent anti-androgen, called cyproterone acetate. 


'The substance cyproterone acetate contained in Estelle-35 ED blocks the effect of endogenously produced and exogenously administered androgens at the target organs by means of competitive inhibition.'


Cyproterone acetate suppresses the actions of testosterone (and its metabolite dihydrotestosterone) on tissues in the body. It is an antagonist to the androgen receptor. This means that it acts by blocking androgen receptors to prevent androgens from binding to the receptor site. It also has an anti-gonadotropic effect on the brain. Cyproterone acetate suppresses luteinising hormone (LH) to decrease concentrations of androgens like testosterone in the blood. This has a negative feedback effect on the hypothalamic pituitary ovarian (HPO) axis and inhibits androgen synthesising enzymes. 


Let's stop and recap. Cyproterone acetate acts to block androgens at its end destination (the receptor site) and breaks its major supply chain (in females, the HPO axis).


The synthetic estrogen in Estelle-35 is called Ethinylestradiol. This substances is often used in OC pills. It is a synthetic copy of the natural estrogen, estradiol. In Estelle-35, Ethinylestradiol amplifies the anti-androgen effect of cyproterone acetate. It upregulates the synthesis of Sex hormone binding globulin (SHBG) in the blood. This helps to block androgens because SHBG binds to testosterone and essentially locks it up so the body can't readily use it.


Quick recap. Ethinylestradiol helps to reduce the amount of free, biologically available androgens in circulation. 


Both compounds are metabolised in the liver.


Lesson # 2.  It doesn't have a simple isolated effect. Estelle-35 doesn't just act on your skin or oily hair. The anti-androgen effect extends to other androgen sites in the body.


The leaflet for Estelle-35 makes it sound like Cyproterone acetate enters the body and happily binds to the androgen receptor in the sebaceous gland to stop acne and oily hair. But it doesn't happen like that.


Aside from basic biochemistry 101, here's a couple of clues in the Product Information that reveal it's not an isolated effect.


'After oral administration cyproterone acetate is completely bioavailable.'


...


'The use of Estelle-35 ED may influence the results of certain laboratory tests, including biochemical parameters of liver, thyroid, adrenal and renal function, plasma levels of carrier proteins, e.g. corticosteroid binding globulin and lipid or lipoprotein fractions, parameters of carbohydrate metabolism and parameters of coagulation and fibrinolysis.'


Translation: it affects the rest of the body!


Synthetic hormones in an OC pill don't just suppress the HPO axis, they affect other systems in the body too. Like antibiotics, the effects are not just felt by the thing you'd like to eliminate or control. The drug has far broader ramifications.


My take on this (a decade too late)


I can't believe that I trained for four years to build muscle while taking an androgen blocker and I didn't even realise! If you're a body builder or athlete that is focused on gaining muscle and becoming stronger, the last thing you'd probably do (unless there's a reason unique to you) is pump an androgen blocker into your body. I'm frustrated that I blindly did that. I'm also curious to see the results that happen after eliminating this hidden road block.


Lesson # 3. You're supposed to stop taking it after the condition clears


'Estelle-35 ED should be withdrawn 3 to 4 cycles after the treated condition has completely resolved. Repeat course of Estelle-35 ED may be given if the androgen-dependent condition(s) recur.'


This is a Catch 22. The Product Information says that 'Treatment will probably need to be continued for about 6 months and probably much longer to gain an acceptable therapeutic effect'. After that, are you really going to happily stop taking the pill that has eliminated your problem? I certainly didn't - quite the opposite. I used Estelle-35 for my acne, and my skin magically cleared. I fretted that I'd stop taking it and I'd just have acne again.


Ten years later, I changed to another OC pill. At 25 years old, I didn't expect to see my skin break out like it did as a 15 year old girl. But sure enough, my acne flared again. I even developed a stubborn rash like condition and small lesions around my mouth and chin. It lasted for almost 6 months. I told my doctor that I'd like to start taking Estelle-35 again to clear my skin. No red flags raised, just another script. Still, it bothered me that this pill seemed to just mask my hormones for all of that time and as soon as I cut off the synthetic supply, it all unravelled again. Had I basically just pressed pause on my puberty for a full decade? About 6 months later, I stopped that pill and tried a different OC pill called the Mini pill for another year. Soon after that, I decided to come off the OC pill entirely.


Lesson # 4.  It is not recommended solely for contraception


If a woman taking Estelle-35 also needs contraception, she can use it for this reason too because (like other OC pills) it stops her ovulating. But the data sheet clearly says that you shouldn't take Estelle-35 just for contraception.


'Estelle-35 ED is not recommended in women solely for contraception. Estelle-35 ED provides effective oral contraception in women being treated for androgen-dependent diseases.'


I don't think my doctor ever asked me if I still took this pill after my acne cleared, or the reasons I'd continued to take it. If the patient doesn't realise this and keep tabs on it, is the doctor?


Lesson # 5.  It can create insulin resistance, affect glucose tolerance and deplete nutrients


There's actually a one liner on carbohydrate metabolism in the Product Information sheet. It says that:


'Depending on the nature and amount of their active substances, ovulation inhibitors may lead to an excessive glucose and plasma insulin reaction (reduced glucose tolerance). The changes are generally reversible after discontinuation of medication.' 


This applies to all OC pills.


There's also a brief mention of other related nutrient deficiencies. Estelle-35 can disturb folic acid metabolism and deplete vitamin B 12 and vitamin B 6. It also has an unpredictable effect on cholesterol levels.


Lesson # 6.  There's side effects


More than 1 per cent of users report nausea, abdominal pain, headaches, depressed or altered mood, weight gain or breast pain while on Estelle-35. That's 1 in 100 women! 


And then there's the serious stuff. Estelle-35 increases the risk of venous and arterial thromboembolism more than other OC pills do. I didn't realise that. It's small, but significant. In fact, in 2018 an Australian Committee on Medicines assessed Estelle-35 to decide its fate because the pill had been linked to an increased incidence of blood clotting in some patients (France briefly banned it, and it has never been approved for use in the United States.) The Committee ruled that a GP can continue to prescribe Estelle-35, but only after checking the patient's family history for a predisposition to blood clotting.


The take away message


This isn't an anti-pill rant to cast the pill as 'bad'. It's to prompt you to think critically about that pill you're taking or thinking about taking - all pills, not just the OC pill - and its possible effects on you. It might be the right decision. It might not. The main thing is to put your drug under cross examination before you decide to put it into your body.


Fem Chem extraordinaire Victoria Felkar suggests 'dating your drug' - getting to know it before you decide if you like it. I wish I did that. Instead, I committed to my drug of choice for a decade after only just meeting one another.


I didn't think critically before I started taking the pill. I didn't think critically about stopping taking it. I could have handled both decisions better. I accepted the script offered to me and I automatically continue to fill it for a decade. This is 'normal', but it's far from ideal. It's taken years, but my body is finally recalibrating to making its hormones. I'm having the acne break outs all over again. But I'm also stronger in training and more energetic in life. I'll take the pimples and be patient.


Your weaponry to interrogate your drug


There's many tools available to you to interrogate your pill (and, if you're game, your doctor's prescription).


Product specific information


If you're in Australia, a useful starting point is The Australian Register of Therapeutic Goods. It includes the basic Consumer Medicines Information (the leaflet you'll find it the package) and a detailed Product Information sheet for drugs available in Australia. This Register helps you to find the precise brand that you're interested in and what's in it. Trading names and chemical compositions may differ among countries, so make sure you check that your research matches your product. The Product Information sheet tells you far more about the drug's pharmacology, including details about its mechanism of action, dosage and administration, absorption and metabolism, bioavailability, half life, elimination, related nutrients, contraindications, interactions with other medicines and adverse effects.


Compound specific information


DrugBank and PubChem are your online drug encyclopaedias. A lot of the information is scientific and difficult to decipher, but you'll pick up some valuable details about the things that the compounds in the drug actually do in the body. Plus, you can access the information free from the shackles of the drug company's clever wording. Remember, the pamphlet for a drug presents the 'facts', but it's also a document related to a product that's sold for profits.


There's no one right decision. But in each case, there's plenty of questions. And it can only help to ask.